Download PDF
Z Gastroenterol 2000; 38(10): 855-872
DOI: 10.1055/s-2000-10001
Übersicht
© Karl Demeter Verlag im Georg Thieme Verlag Stuttgart · New York

Mechanismen der Antigenaufnahme im Dünn- und Dickdarm: die Rolle der M-Zellen für die Initiierung von Immunantworten*

A. Gebert1 , M. Göke2 , H. J. Rothkötter1 , Chr F. Dietrich3
  • Abt. Funktionelle und Angewandte Anatomie, Medizinische Hochschule Hannover
  • Abt. Gastroenterologie und Hepatologie, Medizinische Hochschule Hannover
  • Medizinische Klinik II, J.-W.-Goethe-Universitätsklinikum, Frankfurt/Main
Further Information

Publication History

15.2.2000

20.3.2000

Publication Date:
31 December 2000 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Die darmassoziierten lymphatischen Gewebe, wie z. B. Peyer-Plaques und Appendix, nehmen ständig potenzielle Antigene aus dem Lumen auf, um gegebenenfalls eine spezifische Immunantwort einzuleiten. Dieses „Antigen-Sampling” erfolgt durch M-Zellen, spezialisierte Epithelzellen der Dome-Areale. M-Zellen weisen eine besondere Ultrastruktur auf und sind typischerweise in Kontakt mit intraepithelialen Lymphozyten. Durch Endozytose nehmen die M-Zellen Makromoleküle, Partikel und ganze Mikroorganismen an ihrer apikalen Membran auf, transportieren diese in Vesikeln zur basolateralen Membran und geben sie durch Exozytose zum Interzellularraum ab. Diese Übersicht umreißt die strukturellen und funktionellen Eigenschaften von M-Zellen im Verdauungstrakt des Menschen und verschiedener Labortiere. Spezialisierungen der M-Zellen für Antigenaufnahme und -transport umfassen u. a. die Zusammensetzung der apikalen Membran, ein im Vergleich zu Enterozyten modifiziertes Zytoskelett sowie eine taschenartige Einstülpung der basolateralen Membran, in der sich Lymphozyten und Makrophagen befinden. Die verfügbaren Marker zum Nachweis von M-Zellen werden für verschiedene Spezies vergleichend dargestellt; aktuelle Hypothesen zu Ursprung und Differenzierungsweg von M-Zellen werden zusammengefasst und kritisch diskutiert. Da M-Zellen von zahlreichen Pathogenen, wie z. B. Bakterien und Viren, als Eintrittsstelle benutzt werden und dieser Weg zukünftig für die orale Gabe von Impfstoffen und Medikamenten genutzt werden könnte, wird abschließend ein Überblick über die klinische Bedeutung der Antigenaufnahme durch M-Zellen gegeben.

Mechanisms of antigen uptake in the small and large intestine: The role of M cells in the initiation of immune reactions

The gut-associated lymphoid tissues, e. g., the Peyer’s patches and the appendix, constantly internalize antigenic material to rapidly generate an immune response, if necessary. This sampling of antigens is performed by specialized epithelial cells, the „membranous” or „microfold” (M) cells of the dome epithelia. M cells possess a unique ultrastructure and are typically in contact with lymphoid cells. They endocytose macromolecules and particles, including entire microorganisms, at their apical membrane, transport these in vesicles to their basolateral membrane, and exocytose them to the intercellular space. This article reviews the structural and functional characteristics of M cells in the digestive tract in humans and other species. Specializations of M cells for antigen uptake and transport comprise the composition of their apical membrane, a modified cytoskeleton as compared to enterocytes, and a large pocket-like invagination of the basolateral membrane populated by lymphocytes. Besides ultrastructural characteristics, histochemical markers are listed that are available for detecting M cells. The origin and differentiation pathways of M cells and enterocytes of the dome epithelium are outlined and critically commented on. Because M cells are known entry sites of various pathogens and, in the future, might be employed for the oral application of drugs and vaccines, the clinical relevance of M cells in health and disease is discussed.

Schlüsselwörter

Peyer-Plaques - Membranous (M) Cell - Antigen-Sampling - Immunantwort - Infektion - Vakzination - Mensch

Key words

Peyer’s Patches - Antigen Sampling - Membranous (M) Cell - Immune Response - Infection - Vaccination - Humans

Literatur

  • 1 Bjarnason I, MacPherson A, Hollander D. Intestinal permeability: an overview.  Gastroenterology. 1995;  108 1566-1581
    Google Scholar
  • 2 Mowat A M, Viney J L. The anatomical basis of intestinal immunity.  Immunol Rev. 1997;  156 145-166
    Google Scholar
  • 3 Mayrhofer G, Brooks A. Lymphopoiesis in lymphocyte-filled villi in the small intestine of the rat.  Clin Immumol Immunpathol (Abstract). 1995;  76 S55
    Google Scholar
  • 4 Moghaddami M, Cummins A, Mayrhofer G. Lymphocyte-filled villi: Comparison with other lymphoid aggregations in the mucosa of the human small intestine.  Gastroenterology. 1998;  115 1414-1425
    Google Scholar
  • 5 Kanamori Y, Ishimaru K, Nanno M. et al . Identification of novel lymphoid tissues in murine intestinal mucosa where clusters of c-kit+ IL- 7R+ Thy1+ lympho-hemopoietic progenitors develop.  J Exp Med. 1996;  184 1449-1459
    Google Scholar
  • 6 Saito H, Kanamori Y, Takemori T. et al . Generation of intestinal T cells from progenitors residing in gut cryptopatches.  Science. 1998;  280 275-278
    Google Scholar
  • 7 Scicchitano R, Stanicz A, Ernst P, Bienenstock J. A common mucosal immune system revisited. In: Husband AJ Migration and homing of lymphod cells Orlando; CRC Press 1986 Vol. II: 1-34
    Google Scholar
  • 8 Brandtzaeg P, Baekkevold E S, Farstad I N. et al . Regional specialization in the mucosal immune system: What happens in the microcompartements?.  Immunol Today. 1999;  20 141-151
    Google Scholar
  • 9 Brandtzaeg P, Farstad I N, Haraldsen G. Regional specialization in the mucosal immune system: Primed cells do not always home along the same track.  Immunol Today. 1999;  20 267-277
    Google Scholar
  • 10 Bienenstock J, McDermott M, Befus D, O’Neill M. A common mucosal immunologic system involving the bronchus, breast and bowel.  Edv Exp Med Biol. 1979;  107 53-59
    Google Scholar
  • 11 Westermann J, Pabst R. How organ-specific is the migration of „naive” and „memory” T cells?.  Immunol Today. 1996;  17 278-282
    Google Scholar
  • 12 Croitoru K, Ernst P P. Leukocytes in the intestinal epithelium: An unusual immunological compartment revisited.  Reg Immunol. 1992;  4 63-69
    Google Scholar
  • 13 Shanahan F. The intestinal immune system. In: Johanson LR Physiology of the gastrointestinal tract New York; Raven Press 1994 3rd edidtion: 643-684
    Google Scholar
  • 14 Sim G K. Intraepithelial lymphocytes and the immune system.  Adv Immunol. 1995;  58 297-343
    Google Scholar
  • 15 Ferguson A. Intraepithelial lymphocytes in the small intestine.  Gut. 1977;  18 921-937
    Google Scholar
  • 16 Hirata I, Berrebi G, Austin L L, Keren D F, Dobbins W O. Immunhistological characterization of intraepithelial and lamina propria lymphocytes in control ileum and colon and in inflammatory bowel disease.  Dig Dis Sci. 1986;  31 593-603
    Google Scholar
  • 17 Possier P, Julius M. Intestinal intraepithelial lymphocytes: The plot thickens.  J Exp Med. 1994;  180 1185-1189
    Google Scholar
  • 18 Dobbins W O. Human intestinal intraepithelial lymphocytes.  Gut. 1986;  27 972-98
    Google Scholar
  • 19 Brandtzaeg P, Halstensen T S, Kett K. et al . Immunobiology and immunopathology of human gut mucosa: Humoral immunity and intraepithelial lymphocytes.  Gastroenterology. 1989;  97 1562-1584
    Google Scholar
  • 20 MacDonald T T, Spencer J, Viney J L, Williams C B, Walker-Smith J A. Selective biopsy of Peyer’s patches during ileal endoscopy.  Gastroenterology. 1987;  93 1356-1362
    Google Scholar
  • 21 Biewenga J, Rees E P, Sminia T. Induction and regulation of IgA responses in the microenvironment of the gut.  Clin Immunol Immunpathol. 1993;  67 1-7
    Google Scholar
  • 22 Cebra J J, Shroff K E. Peyer’s patches as inductive sites for IgA commitment. In: Ogra PL, Mestecky J, Lamm ME, Strober W, McGhee JR, Bienenstock J Handbook of mucosal immunology San Diego; Academic Press 1994: 151-158
    Google Scholar
  • 23 Peyer J C. Exercitatio Anatomico-Medica de Glandulis Intestinorum. Schaffhausen; 1677
    Google Scholar
  • 24 Griebel P J, Hein W R. Expanding the role of Peyer’s patches in B-cell ontogeny.  Immunol Today. 1996;  17 30-39
    Google Scholar
  • 25 Cornes J S. Number, size and distribution of Peyer’s patches in the human small intestine.  Gut. 1965;  6 225-233
    Google Scholar
  • 26 Bockman D E, Cooper M D. Pinocytosis by epithelium associated with lymphoid follicles in the bursa of Fabricius, appendix, and Peyer’s patches. An electron microscopic study.  Am J Anat. 1973;  136 455-478
    Google Scholar
  • 27 Owen R L, Jones A L. Epithelial cell specialization within human Peyer’s patches: An ultrastructural study of intestinal lymphoid follicles.  Gastroenterology. 1974;  66 189-203
    Google Scholar
  • 28 Owen R L. Sequential uptake of horseradish peroxidase by lymphoid follicle epithelium of Peyer’s patches in the normal unobstructed mouse intestine: An ultrastructural study.  Gastroenterology. 1977;  72 440-451
    Google Scholar
  • 29 Owen R L, Nemanic P. Antigen processing structures of the mammalian tract: An SEM study of lymphoepithelial organs.  Scanning Electron Microsc. 1978;  11 367-378
    Google Scholar
  • 30 Rosen L, Podjaski B, Bettmann I, Otto H F. Observations on the ultrastructure and function of the so-called „microfold” or membraneous cells (M cells) by means of peroxidase as a tracer.  Virchows Arch [Pathol Anat]. 1981;  390 289-312
    Google Scholar
  • 31 Torres-Medina A. Morphologic characteristics of the epithelial surface of aggregated lymphoid follicles (Peyer’s patches) in the small intestine of newborn gnotobiotic calves and pigs.  Am J Vet Res. 1981;  42 232-236
    Google Scholar
  • 32 Madara J L, Bye W A, Trier J S. Structural features of and cholesterol distribution in M-cell membranes in guinea pig, rat, and mouse Peyer’s patches.  Gastroenterology. 1984;  87 1091-1103
    Google Scholar
  • 33 Rosner A J, Keren D F. Demonstration of M cells in the specialized follicle-associated epithelium overlying isolated lymphoid follicles in the gut.  J Leukocyte Biol. 1984;  35 397-404
    Google Scholar
  • 34 HogenEsch H, Felsburg P J. Ultrastructure and alkaline phosphatase activity of dome epithelium of canine Peyer’s patches.  Vet Immunol Immunopathol. 1990;  24 177-186
    Google Scholar
  • 35 Gebert A, Bartels H. Occluding junctions in the epithelium of the gut-associated lymphoid tissue (GALT) of the rabbit ileum and caecum.  Cell Tissue Res. 1991;  266 301-314
    Google Scholar
  • 36 Liebler E M, Paar M, Pohlenz J F. M cells in the rectum of calves.  Res Vet Sci. 1991;  51 107-114
    Google Scholar
  • 37 Gebert A. Identification of M-cells in the rabbit tonsil by vimentin immuno-histochemistry and in vivo protein transport.  Histochem Cell Biol. 1995;  104 211-220
    Google Scholar
  • 38 Gebert A, Bartels H. Ultrastructure and protein transport of M cells in the rabbit cecal patch.  Anat Rec. 1995;  241 487-495
    Google Scholar
  • 39 Lowden S, Heath T. Lymphoid tissues of the ileum in young horses: Distribution, structure, and epithelium.  Anat Embryol. 1995;  192 171-179
    Google Scholar
  • 40 Beier R, Gebert A. Kinetics of particle uptake in the domes of Peyer’s patches.  Am J Physiol. 1998;  275 G130-137
    Google Scholar
  • 41 Owen R L, Pierce N F, Apple R T, Cray W C. M cell transport of Vibrio cholerae from the intestinal lumen into Peyer’s patches: A mechanism for antigen sampling and for microbial transepithelial migration.  J Infect Dis. 1986;  153 1108-1118
    Google Scholar
  • 42 Sanderson I R, Walker W A. Uptake and transport of macromolecules by the intestine: Possible role in clinical disorders (an update).  Gastroenterology. 1993;  104 622-639
    Google Scholar
  • 43 Bye W A, Allan C H, Trier J S. Structure, distribution, origin of M cells in Peyer’s patches of mouse ileum.  Gastroenterology. 1984;  86 789-801
    Google Scholar
  • 44 Neutra M R, Phillips T L, Mayer E L, Fishkind D J. Transport of membrane-bound macromolecules by M cells in follicle-associated epithelium of rabbit Peyer’s patch.  Cell Tissue Res. 1987;  247 537-546
    Google Scholar
  • 45 Atkins A M, Schofield G C. Lymphoglandular complexes in the large intestine of the dog.  J Anat. 1972;  113 169-178
    Google Scholar
  • 46 Naukkarinen A, Arstilla A U, Sorvari T E. Morphological and functional differentiation of the surface epithelium of the bursa Fabricii in chicken.  Anat Rec. 1978;  191 415-432
    Google Scholar
  • 47 Beezhold D H, Sachs H G, Van Alten P J. The development of transport ability by embryonic follicle-associated epithelium.  J Reticuloendothel Soc. 1983;  34 143-152
    Google Scholar
  • 48 Hanger J J, Heath T J. The arrangement of gut-associated lymphoid tissue and lymph pathways in the koala (Phascolarctos cinereus).  J Anat. 1994;  185 129-134
    Google Scholar
  • 49 Davenport W D, Allen E R. Dome epithelium and follicle-associated basal lamina pores in the avian bursa of Fabricius.  Anat Rec. 1995;  241 155-162
    Google Scholar
  • 50 Owen R L, Ermak T H. Structural specializations for antigen uptake and processing in the digestive tract.  Springer Semin Immunopathol. 1990;  12 139-152
    Google Scholar
  • 51 Smith M W, Peacock M A. „M” cell distribution in follicle-associated epithelium of mouse Peyer’s patch.  Am J Anat. 1980;  159 167-175
    Google Scholar
  • 52 Smith M W, Jarvis L G, King I S. Cell proliferation in follicle-associated epithelium of mouse Peyer’s patch.  Am J Anat. 1980;  159 157-166
    Google Scholar
  • 53 Clark M A, Jepson M A, Simons N L, Booth T A, Hirst B H. Differential expression of lectin-binding sites defines mouse intestinal M-cells.  J Histochem Cytochem. 1993;  41 1679-1687
    Google Scholar
  • 54 Clark M A, Jepson M A, Simons N L, Hirst B H. Differential surface characteristics of M cells from mouse intestinal Peyer’s patches and caecal patches.  Histochem J. 1994;  26 271-280
    Google Scholar
  • 55 Gebert A, Fassbender S, Werner K, Weißferdt A. The development of M cells in Peyer’s patches is restricted to specialized dome-associated crypts.  Am J Pathol. 1999;  154 1573-1582
    Google Scholar
  • 56 Pappo J, Steger H J, Owen R L. Differential adherence of epithelium overlying gut-associated lymphoid tissue.  Lab Invest. 1988;  58 692-697
    Google Scholar
  • 57 Gebert A, Hach G, Bartels H. Co-localization of vimentin and cytokeratins in M-cells of rabbit gut-associated lymphod tissue (GALT).  Cell Tissue Res. 1992;  269 331-340
    Google Scholar
  • 58 Jepson M A, Simmons N L, Hirst G L, Hirst B H. Identification of M cells and their distribution in rabbit intestinal Peyer’s patches and appendix.  Cell tissue Res. 1993;  273 127-136
    Google Scholar
  • 59 Gebert A, Rothkötter H J, Pabst R. Cytokeratin 18 is an M-cell marker in porcine Peyer’s patches.  Cell Tissue Res. 1994;  276 213-221
    Google Scholar
  • 60 Meynell H M, Thomas N W, James P S. et al . Up-regulation of microsphere transport across the follicle-associated epithelium of Peyer’s patch by exposure to Streptococcus pneumoniae R36a.  FASEB J. 1999;  13 611-619
    Google Scholar
  • 61 Bhalla D K, Owen R L. Cell renewal and migration in lymphoid follicles of Peyer’s patches and cecum - an autoradiographic study in mice.  Gastroenterology. 1982;  82 232-242
    Google Scholar
  • 62 Morfitt D C, Pohlenz J FL. Porcine colonic lymphoglandular complex: Distribution, structure, and epithelium.  Am J Anat. 1989;  184 41-51
    Google Scholar
  • 63 Giannasca P J, Giannasca K T, Falk P, Gordon J I, Neutra M R. Regional differences in glycoconjugates of intestinal M cells in mice: Potential targets for mucosal vaccines.  Am J Physiol. 1994;  267 G1108-1121
    Google Scholar
  • 64 Gebert A, Hach G. Differential binding of lectins to M cells and enterocytes in the rabbit cecum.  Gastroenterology. 1993;  105 1350-1361
    Google Scholar
  • 65 Jepson M A, Clark M A, Simmons N L, Hirst B H. Epithelial M cells in the rabbit caecal lymphoid patch display distinctive surface characteristics.  Histochemistry. 1993;  100 441-447
    Google Scholar
  • 66 Sicinski P, Rowinsky J, Warchol J B, Bem W. Morphometric evidence against lymphocyte-induced differentiation of M cell from absorptive cells in mouse Peyer’s patches.  Gastroenterology. 1986;  90 609-616
    Google Scholar
  • 67 Schmedtje J F. Some histochemical characteristics of lymphoepithelial cells of the rabbit appendic (Abstract).  Anat Rec. 1965;  151 412-413
    Google Scholar
  • 68 Owen R L, Bhalla D K. Cytochemical analysis of alkaline phosphatase and esterase activities and of lectin-binding and anionic sites in rat and mouse Peyer’s patch M cells.  Am J Anat. 1983;  168 199-212
    Google Scholar
  • 69 Farstad I N, Halstensen T S, Fausa O, Brandtzaeg P. Heterogeneity of M-cell-associated B and T cells in human Peyer’s patches.  Immunology. 1994;  83 457-464
    Google Scholar
  • 70 Savidge T C, Smith M W, Mayel-Afshar S, Collins A J, Freeman T C. Selective regulation of epithelial gene expression in rabbit Peyer’s patch tissue.  Pflügers Arch. 1994;  428 391-399
    Google Scholar
  • 71 Pappo J. Generation and characterization of monoclonal antibodies recognizing follicle epithelial M cells in rabbit gut-associated lymphoid tissues.  Cell Immunol. 1989;  120 31-41
    Google Scholar
  • 72 Pappo J, Ermak T H, Steger H J. Monoclonal antibody-directed targeting of fluorescent polystyrene microspheres to Peyer’s patch M cell.  Immunology. 1991;  73 277-280
    Google Scholar
  • 73 Roy M J, Ruiz A, Varvayanis M. A novel antigen is common to the dome epithelium of gut- and bronchus-associated lymphoid tissues.  Cell Tissue Res. 1987;  248 635-644
    Google Scholar
  • 74 Falk P, Roth K A, Gordon J I. Lectins are sensitive tools for defining the differentiation programs of mouse gut epithelial cell lineages.  Am J Physiol. 1994;  266 G987-G1003
    Google Scholar
  • 75 Gebert A, Posselt W. Glycoconjugate expression defines the origin and differentiation pathway of intestinal M-cells.  J Histochem Cytochem. 1997;  45 1341-1350
    Google Scholar
  • 76 Ingber D E. Cellular tensegrity: Defining new rules of biological design that governs the cytoskeleton.  J Cell Sci. 1993;  104 613-627
    Google Scholar
  • 77 Jepson M A, Mason C M, Bennett M K, Simmons N L, Hirst B H. Co-expression of vimentin and cytokeratins in M cells of rabbit intestinal lymphoid follicle-associated epithelium.  Histochem J. 1992;  24 33-39
    Google Scholar
  • 78 Gebert A. M-cells in the rabbit tonsil exhibit distinctive glycoconjugates in their apical membrane.  J Histochem Cytochem. 1996;  44 1033-1042
    Google Scholar
  • 79 Gebert A, Hach G. Vimentin antibodies stain membranous epithelial cells in the rabbit bronchus-associated lymphoid tissue (BALT).  Histochemistry. 1992;  98 271-273
    Google Scholar
  • 80 Gebert A. M cells in the rabbit palatine tonsil: The distribution, spatial arrangement and membrane subdomains as defined by confocal lectin histochemistry.  Anat Embryol. 1997;  195 353-358
    Google Scholar
  • 81 Gebert A, Rothkötter H J, Pabst R. M cells in Peyer’s patches of the intestine.  Int Rev Cytol. 1996;  167 91-159
    Google Scholar
  • 82 Kucharzik T, Lügering N, Schmid K W. et al . Human intestinal M cells exhibit enterocyte-like intermediate filaments.  Gut. 1998;  42 54-62
    Google Scholar
  • 83 Pappo J, Ermak T H. Uptake and translocation of fluorescent latex particles by rabbit Peyer’s patch follicle epithelium: A quantitative model for M cell uptake.  Clin Exp Immunol. 1989;  76 144-148
    Google Scholar
  • 84 Jepson M A, Simmons N L, Savidge T C, James P S, Hirst B H. Selective binding and transcytosis of latex microspheres by rabbit intestinal M cells.  Cell Tissue Res. 1993;  271 399-405
    Google Scholar
  • 85 Powell D W. Barrier function of epithelia.  Am J Physiol. 1981;  241 G275-288
    Google Scholar
  • 86 Ducroc R, Heyman M, Beaufrere B, Morgat J L, Desjeux J F. Horseradish peroxidase transport across rabbit jejunal and Peyer’s patches in vitro.  Am J Physiol. 1983;  245 G54-G58
    Google Scholar
  • 87 Keljo D J, Hamilton J R. Quantitative determination of macromolecular transport rate across intestinal Peyer’s patches.  Am J Physiol. 1983;  244 G637-644
    Google Scholar
  • 88 Kumagai K. A study about the intestinal absorptive mechanism of morphological compoments.  Osaka Med J. 1922;  21 497-522
    Google Scholar
  • 89 Ogushi R. Über den Eintrittsvorgang der Tuberkelbazillen durch den Darmtraktus und dessen pathogene Bedeutung insbesondere für die Phthisiogenese.  Kekkaku-Zassi (tuberculosis) Vol III. 1925;  7 37-39
    Google Scholar
  • 90 LeFevre M E, Olivo R, Vanderhoff J W, Jeol D D. Accumulation of latex in Peyer’s patches and its subsequent appearance in villi and mesenteric lymph nodes.  Proc Soc Exp Biol Med. 1978;  159 298-302
    Google Scholar
  • 91 Eldridge J H, Staas J K, Meulbroek J A. et al . Biodegradable microspheres as a vaccine delivery system.  Mol Immunol. 1991;  28 287-294
    Google Scholar
  • 92 Jepson M A, Simmons N L, O’Hagan D t, Hirst B H. Comparison of poly(DL-lactido-co-glycolide) and polystyrene microsphere targeting to intestinal M cells.  J Drug Target. 1993;  1 245-249
    Google Scholar
  • 93 Ermak T H, Dougherty E P, Bhagat H R, Kabok Z, Pappo J. Uptake and transport of copolymer biodegradable microspheres by rabbit Peyer’s patch M cells.  Cell Tissue Res. 1995;  279 433-436
    Google Scholar
  • 94 Wolf J L, Rubin D H, Finberg R. et al . Intestinal M-cells: a pathway for entry of reovirus into the host.  Science. 1981;  212 471-472
    Google Scholar
  • 95 Sicinski P, Rowinski J, Warchol J B. Poliovirus type 1 enters the human host through M cells.  Gastroenterology. 1990;  98 56-58
    Google Scholar
  • 96 Amerongen H M, Weltzin R, Farnet C M. et al . Transepithelial transport of HIV- 1 by intestinal M cells: A mechanism for transmission of AIDS.  J Acq Immun Def Synd. 1991;  4 760-765
    Google Scholar
  • 97 Marcial M A, Madara J L. Cryptosporidium: Cellular localization, structural analysis of absorptive cell-parasite membrane-membrane interactions in guinea pigs, and suggestion of protozoan transport by M cells.  Gastroenterology. 1986;  90 83-594
    Google Scholar
  • 98 Inman L R, Cantey I R. Specific adherence of Escherichia coli (strain RDEC- 1) to membranous (M) cells of the Peyer’s patch in Escherichia coli diarrhea in the rabbit.  J Clin Invest. 1983;  71 1-8
    Google Scholar
  • 99 Inman L R, Cantey J R. Peyer’s patch lymphoid follicle epithelial adherence of a rabbit enteropathogenic Eschericia coli (strain RDEC- 1).  J Clin Invest. 1984;  74 90-95
    Google Scholar
  • 100 Walker R I, Schmauder-Chock E A, Parker J L. Selective association and transport of Campylobacter jejuni through M cells of rabbit Peyer’s patches.  Can J Microbiol. 1988;  34 1142-1147
    Google Scholar
  • 101 Perdomo O JJ, Cavaillon J M, Huerre M. et al . Acute inflammation causes epithelial invasion and mucosal destruction in experimental shigellosis.  J Exp Med. 1994;  180 1307-1319
    Google Scholar
  • 102 Jones B D, Ghori N, Falkow S. Salmonella typhimurium initiates murine infection by penetrating and destroying the specialized epithelial M cells of the Peyer’s patches.  J Exp Med. 1994;  180 15-23
    Google Scholar
  • 103 Wolf J L, Kauffman R S, Finberg R. et al . Determinants of reovirus interaction with the intestinal M cells and absorptive cells of murine intestine.  Gastroenterology. 1983;  85 291-300
    Google Scholar
  • 104 Amerongen H M, Wilson G AR, Fields B N, Neutra M R. Proteolytic processing of reovirus is required for adherence to intestinal M cells.  J Virol. 1994;  68 8428-8432
    Google Scholar
  • 105 Moll L K, Cantey J R. Peyer’s patch adherence of enteropathogenic Escherichia coli strain in rabbits.  Infect Immun. 1997;  65 3788-3793
    Google Scholar
  • 106 Yamamoto T, Kamano T, Uchimura M, Iwanaga M, Yokota T. Vibrio cholerae O1 adherence to villi and lymphoid follicle epithelium: In vitro model using formalin-treated human small intestine and correlation between adherence and cell-associated hemagglutinin levels.  Infect Immun. 1988;  56 3241-3250
    Google Scholar
  • 107 Lelouard H, Reggio H, Mangeat P, Neutra M, Montcourrier P. Mucin-related epitopes distinguish M cells and enterocytes in rabbit appendix and Peyer’s patches.  Infect Immun. 1999;  67 357-367
    Google Scholar
  • 108 Giannasca P J, Giannasca K T, Leichtner A M, Neutra M R. Human intestinal M cells display the sialyl Lewis A antigen.  Infect Immun. 1999;  67 946-953
    Google Scholar
  • 109 Foster N, Clark M A, Jepson M A, Hirst B H. Ulex europaeus 1 lectin targets microspheres to mouse Peyer’s patch M-cell in vivo.  Vaccine. 1998;  16 536-541
    Google Scholar
  • 110 Clark M A, Hirst B H, Jepson M A. M-cell surface β1 integrin expression and invasin-mediated targeting of Yersinia pseudotuberculosis to mouse Peyer’s patch M cells.  Infect Immun. 1998;  66 1237-1243
    Google Scholar
  • 111 Giannasca P J, Neutra M R. Interactions of microorganisms with intestinal M cells: Mucosal invasion and induction of secretory immunity.  Infect Agents Dis. 1994;  2 242-248
    Google Scholar
  • 112 Frey A, Giannasca K T, Weltzin R. et al . Role of the glycocalyx in regulating access of microparticles to apical plasma membranes of intestinal epithelial cells: Implications for microbial attachment and oral vaccine targeting.  J Exp Med. 1996;  184 1045-1059
    Google Scholar
  • 113 Killian M, Mestecky J, Russell M W. Defense mechanisms involving Fc-dependent functions of immunoglobulin A and their subversion by bacterial immunoglobulin A proteases.  Microbiol Rev. 1988;  52 296-303
    Google Scholar
  • 114 Krahenbuhl J P, Neutra M R. Molecular and cellular basis of immune protection of mucosal surfaces.  Physiol Rev. 1992;  72 853-879
    Google Scholar
  • 115 Weltzin R, Lucia-Jandris P, Michetti P. et al . Binding and transepithelial transport of immunoglobulins by intestinal M cells: Demonstration using monoclonal IgA antibodies against enteric viral proteins.  J Cell Biol. 1989;  108 1673-1685
    Google Scholar
  • 116 Kato T. A study of secretory immunoglobulin A on membranous epithelial cells (M cells) and adjacent absorptive cells of rabbit Peyer’s patches.  Gastroenterol Jpn. 1990;  25 15-23
    Google Scholar
  • 117 Porta C, James P S, Phillips A D. et al . Confocal analysis of fluorescent bead uptake by mouse Peyer’s patch follicle-associated M cells.  Exp Physiol. 1992;  77 929-932
    Google Scholar
  • 118 Bjerke K, Brandtzaeg P, Fausa O. T cell distribution is different in follicle-associated epithelium of human Peyer’s patches and villous epithelium.  Clin Exp Immunol. 1988;  74 270-275
    Google Scholar
  • 119 Pappo J, Owen R L. Absence of secretory component expression by epithelial cells overlying rabbit gut-associated lymphoid tissue.  Gastroenterology. 1988;  95 1173-1177
    Google Scholar
  • 120 Futter C, Marsh M. Endocytosis and pasta.  Trends Cell Biol. 1993;  3 316-318
    Google Scholar
  • 121 Inman L R, Cantey J R, Formal S B. Colonization, virulence, and mucosal interaction of an enteropathogenic Escherichia coli (strain RDEC- 1) expressing Shigella somatic antigen in the rabbit intestine.  J Infect Dis. 1986;  154 742-751
    Google Scholar
  • 122 Jepson M A, Clark M A, Simmons N L, Hirst B H. Actin accumulation sites of attachment of indigenous apathogenic segmented filamentous bacteria to mouse ileal epithelial cells.  Infect Immun. 1993;  61 4001-4004
    Google Scholar
  • 123 Clark M A, Jepson M A, Simmons N L, Hirst B H. Preferential interaction of Salmonella typhimurium with mouse Peyer’s patch M cells.  Res Microbiol. 1994;  145 543-552
    Google Scholar
  • 124 Francis C L, Ryan T A, Jones B D, Smith S J, Falkow S. Ruffles induced by Salmonella and other stimuli direct macropinocytosis of bacteria.  Nature. 1993;  364 638-642
    Google Scholar
  • 125 Blok J, Mulder-Stapel A A, Ginsel L A, Daems W T. Endocytosis in absorptive cells of cultured human small-intestinal tissue: horseradish peroxidase, lactoperoxidase, and ferritin as markers.  Cell Tissue Res. 1981;  216 1-13
    Google Scholar
  • 126 Owen R L, Apple R T, Bhalla D K. Morphometric and cytochemical analysis of lysosomes in rat Peyer’s patch follicle epithelium: Their reduction in volume fraction and acid phosphatase content in M cells compared to adjacent enterocytes.  Anat Rec. 1986;  216 521-527
    Google Scholar
  • 127 Allan C H, Mendrick D L, Trier J S. Rat intestinal M cells contain acidic endosomal-lysosomal compartments and express class II major histocompatibility complex determinants.  Gastroenterology. 1993;  104 698-708
    Google Scholar
  • 128 Bennett K, Levine T, Ellis J S. et al . Antigen processing for presentation by class II major histocompatibility complex requires cleavage by cathepsin E.  Eur J Immunol. 1992;  22 1519-1524
    Google Scholar
  • 129 Finzi G, Cornaggia M, Capella C. et al . Cathepsin E in follicle associated epithelium of intestine and tonsils: Localization to M cells and possible role in antigen processing.  Histochemistry. 1993;  99 201-211
    Google Scholar
  • 130 Kirschner M, Weber K. Cytoplasm and cell motility.  Curr Opin Cell Biol. 1989;  1 3-4
    Google Scholar
  • 131 Gebert A, Willführ B, Pabst R. The rabbit M-cell marker vimentin is present in epithelial cells of the tonsil crypt.  Acta Otolaryngol (Stockh). 1995;  115 697-700
    Google Scholar
  • 132 Kracke A, Bartels H. Colchicine inhibits transcytosis in M-cells of mouse Peyer’s patches (Abstract).  Mol Biol Cell. 1994;  5 43a
    Google Scholar
  • 133 Jarry A, Robaszkiewicz M, Brousse N, Potet F. Immune cells associated with M cells in the follicle-associated epithelium of Peyer’s patches in the rat. An electron- and immunoelectron-microscopic study.  Cell Tissue Res. 1989;  255 293-298
    Google Scholar
  • 134 Rautenberg K, Cichon C, Heyer G, Demel M, Schmidt M A. Immunocytochemical characterization of the follicle-associated epithelium of Peyer’s patches: Anti-cytokeratin 8 antibody (clone 4.1.18) as a molecular marker for rat M cells.  Eur J Cell Biol. 1996;  71 363-370
    Google Scholar
  • 135 Kernéis S, Bogdanova A, Colucci-Guyon E, Kraehenbuhl J P, Pringault E. Cytosolic distribution of villin in M cells from mouse Peyer’s patches correlates with the absence of a brush border.  Gastroenterology. 1996;  110 515-521
    Google Scholar
  • 136 Gebert A, Jepson M A. Is the epithelial origin of M cells controversial?.  (Letter) Gastroenterology. 1996;  111 1163
    Google Scholar
  • 137 Schmedtje J F. Lymphocyte positions in the dome epithelium of the rabbit appendix.  J Morphol. 1980;  166 179-195
    Google Scholar
  • 138 Cheng H, Leblond C P. Origin, differentiation and renewal of the four main epithelial cells types in the mouse small intestine. V. Unitarian theory of the origin of the four epithelial cells types.  Am J Anat. 1974;  141 537-562
    Google Scholar
  • 139 Bjerknes M, Cheng H. Clonal analysis of mouse intestinal epithelial progenitors.  Gastroenterology. 1999;  116 7-14
    Google Scholar
  • 140 Savidge T C. The life and times of an intestinal M cell.  Trend Microbiol. 1996;  4 301-306
    Google Scholar
  • 141 Kernéis S, Bogdanova A, Kraehenbuhl J P, Pringault E. Conversion by Peyer’s patch lymphocytes of human enterocytes into M cells that transport bacteria.  Science. 1997;  277 949-952
    Google Scholar
  • 142 Smith M W, Peacock M A. Lymphocyte induced formation of antigen transporting „M” cells from fully differentiated mouse enterocytes. In: Robinson JWL, Dowling RH, Riecken EO Mechanisms of intestinal adaption Lancaster; MTP 1982 573-583
    Google Scholar
  • 143 Clark M A, Jepson M A, Simmons N L, Hirst B H. Selective binding and transcytosis of Ulex europaeus 1 lectin by mouse Peyer’s patch M-cells in vivo.  Cell Tissue Res. 1995;  282 455-461
    Google Scholar
  • 144 Clark M A, Reed K A, Lodge J. et al . Invasion of murine intestinal M cells by Salmonella typhimurium inv mutants severely deficient for invasion of cultured cells.  Infect Immun. 1996;  64 4363-4368
    Google Scholar
  • 145 Marth T, Kelsall B L, Strober W, Zeitz M. Mechanismen und Anwendung oraler Toleranz.  Z Gastroenterol. 1999;  37 165-185
    Google Scholar
  • 146 Ermak T H, Owen R L. Differential distribution of lymphcytes and accessory cells in mouse Peyer’s patches.  Anat Rec. 1986;  215 144-152
    Google Scholar
  • 147 Bjerke K, Halstensen T S, Jahnsen F, Pulford K, Brandtzaeg P. Distribution of macrophages and granulocytes expressing L1 protein (calprotectin) in human Peyer’s patches compared with normal ileal lamina propria and mesenteric lymph nodes.  Gut. 1993;  34 1357-1363
    Google Scholar
  • 148 Kohbata S, Yokoyama H, Yabuuchi E. Cytopathogenic effect of Salmonella typhi GIFU 10 007 on M cells of murine ileal Peyer’s patches in ligated ileal loops: an ultrastructural study.  Microbiol Immunol. 1986;  30 1225-1237
    Google Scholar
  • 149 Owen R L, Nemanic P C, Stevens D P. Ultrastructural observations on giardiasis in a murine model. I. Intestinal distribution, attachment, and relationship to the immune system of Giardia muris.  Gastroenterology. 1979;  76 757-769
    Google Scholar
  • 150 Jepson M A, Clark M A. Studying M cells and their role in infection.  Trends Microbiol. 1998;  9 359-365
    Google Scholar
  • 151 Salk D. Eradication of poliomyelitis in the United States: III. Poliovaccines - practical considerations.  Rev Infect Dis. 1980;  2 258-273
    Google Scholar
  • 152 Ivanoff B, Levine M M, Lambert P H. Vaccination against typhoid fever: Present status.  Bull World Health Organ. 1994;  72 957-971
    Google Scholar
  • 153 Shalaby W SW. Development of oral vaccines to stimulate mucosal and systemic immunity: barriers and novel strategies.  Clin Immunol Immunopathol. 1995;  74 127-134
    Google Scholar
  • 154 Eldridge J H, Staas J K, Meulbroek J A, Tice T S, Gilley R M. Biodegradable and biocompatible poly(DL-lactide-co-glycolide) microspheres as and adjuvant for staphylococcal enterotoxin B toxoid which enhances the level of toxin-neutralizing antibodies.  Infect Immun. 1991;  59 2978-2986
    Google Scholar
  • 155 Maloy K J, Donachie A m, O’Hagan D T, Mowat A M. Induction of mucosal and systemic immune responses by immunization with ovalbumin entrapped in poly(lactide-co-glycolide) microparticles.  Immunology. 1994;  81 661-667
    Google Scholar
  • 156 Wachsmann D, Klein J P, Scholler M. et al . Serum and salivary antibody responses in rats orally immunized with Streptococcus mutans carbohydrate protein conjugate associated with liposomes.  Infect Immun. 1986;  52 408-413
    Google Scholar
  • 157 Mowat A M, Maloy K J, Donachie A M. Immune-stimulating complexes as adjuvants for inducing local and systemic immunity after oral immunization with protein antigens.  Immunology. 1993;  80 527-534
    Google Scholar
  • 158 O’Hagan D T, Rahman D, McGee J P. et al . Biodegradable microparticles as controlled release antigen delivery systems.  Immunology. 1991;  73 239-242
    Google Scholar
  • 159 Panja A, Mayer L. Diversity and function of antigen-presenting cells in mucosal tissues. In: Ogra PL, Strober W, Mestecky J, McGhee JR, Lamm ME, Bienenstock J Handbook of mucosal immunology San Diego; Academic Press 1994: 177-183
    Google Scholar
  • 160 Wolf J L, Dambrauskas R, Sharpe A H, Trier J S. Adherence to and penetration of the intestinal epithelium by reovirus type 1 in neonatal mice.  Gastroenterology. 1987;  92 82-91
    Google Scholar
  • 161 Savidge T C, Smith M W, James P S, Aldred P. Salmonella-induced M-cell formation in germfree mouse Peyer’s patch tissue.  Am J Pathol. 1991;  139 177-184
    Google Scholar
  • 162 Regoli M, Borghesi C, Bertelli E, Nicoletti C. Uptake of a gram-positive bacterium (Streptococcus pneumoniae R36a) by M cells of rabbit Peyer’s patches.  Ann Anat. 1995;  177 119-124
    Google Scholar
  • 163 Borghesi C, Regoli M, Bertelli E, Nicoletti C. Modifications of the follicle-associated epithelium by short-term exposure to a non-intestinal bacterium.  J Pathol. 1996;  180 326-332
    Google Scholar
  • 164 Borghesi C, Taussig M J, Nicoletti C. Rapid appearance of M cells after microbial challenge is restricted at the periphery of the follicle-associated epithelium of Peyer’s patch.  Lab Invest. 1999;  79 1393
    Google Scholar
  • 165 Roy M J, Walsh T J. Histopathologic and immunohistochemical changes in gut-associated lymphoid tissues after treatment of rabbits with dexamethasone.  Lab Invest. 1992;  64 437-443
    Google Scholar
  • 166 Savidge T C, Smith M W. Cyclosporin-A reduces M cell numbers in antigen-stimulated mouse Peyer’s patches (Abstract).  J Physiol. 1990;  442 84P
    Google Scholar
  • 167 Cuvelier C A, Quatacker J, Mielants H, Vos M, Veys E, Roels H J. M-cells are damaged and increased in number inflamed human ileal mucosa.  Histopathology. 1994;  24 417-426
    Google Scholar
  • 168 Smith M W. Selective expression of brush border hydrolases by mouse Peyer’s patch and jejunal villus enterocytes.  J Cell Physiol. 1985;  124 219-225
    Google Scholar
  • 169 Montcourrier P, Lelouard H, Mangeat P, Reggio H. Apical membranes from M-cells and enterocytes have different binding capacity for monoclonal antibodies in rabbit appendix and Peyer’s patches (Abstract).  Mol Biol Cell. 1996;  7 89a
    Google Scholar
  • 170 Liebler E M, Lemke C, Pohlenz J F. Ultrastructural study of the uptake of ferritin by M cells in the follicle-associated epithelium in the small and large intestines of pigs.  Am J Vet Res. 1995;  56 725-730
    Google Scholar
  • 171 Joel D D, Laissue J A, LeFevre M E. Distribution and fate of ingested carbon particles in mice.  J Reticuloendothel Soc. 1978;  24 477-487
    Google Scholar
  • 172 Amerongen H M, Weltzin R, Mack J A. M cell-mediated antigen transport and monoclonal IgA antibodies for mucosal immune protection.  Ann NY Acad Sci. 1992;  664 18-26
    Google Scholar
  • 173 Childers N K, Denys F R, McGee N F, Michalek S M. Ultrastructural study of liposome uptake by M cells of rat Peyer’s patch: An oral vaccine system for delivery of purified antigen.  Reg Immunol. 1990;  3 8-16
    Google Scholar
  • 174 Woode G N, Pohlenz J F, Gourley N E, Fagerland J A. Astrovirus and Breda virus infections of dome cell epithelium of bovine ileum.  J Clin Microbiol. 1984;  19 623-630
    Google Scholar
  • 175 Neutra M R, Kraehenbuhl J P. Transepithelial transport and mucosal defence I: The role of M cells.  Trends Cell Biol. 1992;  2 134-138
    Google Scholar
  • 176 Fujimura Y. Functional morphology of microfold cells (M cells) in Peyer’s patches: Phagocytosis and transport of BCG by M cells into rabbit Peyer’s patches.  Gastroenterol Jpn. 1986;  21 325-335
    Google Scholar
  • 177 Ackermann M R, Cheville N F, Deyoe B L. Bovine ileal dome lymphoepithelial cells: Endocytosis and transport of Brucella abortus strain 19.  Vet Pathol. 1988;  25 28-35
    Google Scholar
  • 178 Momotani E, Whipple D L, Thiermann A B, Cheville N F. Role of M cells and macrophages in the entrance of Mycobacterium paratuberculosis into domes of ileal Peyer’s patches in calves.  Vet Pathol. 1988;  25 131-137
    Google Scholar
  • 179 Grützkau A, Hanski C, Hahn H, Riecken E O. Involvement of M cells in the bacterial invasion of Peyer’s patches: A common mechanism shared by Yersinia enterocolitica and other enteroinvasive bacteria.  Gut. 1990;  31 1011-1015
    Google Scholar
  • 180 Autenrieth I B, Firsching R. Penetration of M cells and destruction of Peyer’s patches by Yersinia enterocolitica: An ultrastructural and histological study.  J Med Microbiol. 1996;  44 285-294
    Google Scholar

Fußnoten

1 Unterstützt durch die Deutsche Forschungsgemeinschaft (SFB 280/C14, A17, C1)

Anschrift für die Verfasser

Priv.-Doz. Dr. med. Andreas Gebert

Abteilung Anatomie 2

Medizinische Hochschule Hannover

30623 Hannover

Email: Gebert.Andreas@mh-hannover.de

      >