Thromb Haemost 2001; 85(05): 845-851
DOI: 10.1055/s-0037-1615758
Review Article
Schattauer GmbH

Factor XIII of Blood Coagulation as a Nuclear Crosslinking Enzyme

Róza Ádány*
1   Department of Preventive Medicine, School of Public Health
,
Helga Bárdos*
1   Department of Preventive Medicine, School of Public Health
,
Miklós Antal
2   Department of Anatomy, Histology and Embryology, Medical and Health Science Center, University of Debrecen, Hungary
,
László Módis
2   Department of Anatomy, Histology and Embryology, Medical and Health Science Center, University of Debrecen, Hungary
,
Attila Sárváry
1   Department of Preventive Medicine, School of Public Health
,
Sándor Szücs
1   Department of Preventive Medicine, School of Public Health
,
Imre Balogh
1   Department of Preventive Medicine, School of Public Health
› Author Affiliations
Further Information

Publication History

Received 03 July 2000

Accepted after resubmission 02 February 2001

Publication Date:
11 December 2017 (online)

Summary

Intracellular localization and distribution of Factor XIII subunit A (FXIIIA) was investigated in association with monocyte-macrophage differentiation in a long term culture of human monocytes by light-and electron microscopical as well as biochemical and immunobio-chemical techniques. To allow the detection of FXIIIA in cells with well-preserved ultrustructure, immunosera against glutaraldehydederivatized recombinant FXIIIA were developed in rabbits, then characterized and used in this study. In the early phase of macrophage differentiation intranuclear accumulation of FXIIIA was detected as a transient phenomenon in cells of the 2nd day culture by optical sectioning with 0,7 m steps in laser scanning confocal microscopy and immunoblotting technique. FXIIIA could be detected by immuno-electron microscopic postembedding staining over electrodense DNA-containing areas. Fluoresceinated monodansylcadaverine incorporation assay was used to demonstrate that FXIIIA is not only present in the nuclei, but also expresses its transglutaminase activity. Our finding of the nuclear accumulation of FXIIIA in differentiating human macrophages is also unique in that a blood clotting factor has, for the first time, been localized in nuclei and has been shown to be an intracellular crosslinking enzyme. The possible role of nuclear FXIIIA in association with cellular processes involving chromatin structure remodeling, such as cell death, cell differentiation or cellular proliferation requires further in-depth investigation.

* The authors equally contributed, thus they share the first authorship


 
  • References

  • 1 Lorand L, Losowsky MS, Miloszewski KJM. Human factor XIII: fibrin stabilizing factor. Prog Hemostas Thromb 1980; 5: 245-90.
  • 2 Muszbek L, Laki K. Interaction of thrombin with proteins other than fibrinogen (Thrombin susceptible bonds). Activation of factor XIII. In The thrombin. Machovich R. ed. Boca Raton: CRC Press; 1984
  • 3 Kiesselbach TH, Wagner RH. Demonstration of factor XIII in human megakaryocytes by a fluorescent antibody technique. Ann NY Acad Sci 1972; 202: 318-28.
  • 4 Muszbek L, Ádány R, Szegedi G, Polgár J, Kávai M. Factor XIII of blood coagulation in human monocytes. Thromb Res 1985; 37: 401-10.
  • 5 Henriksson P, Becker S, Lynch G, McDonagh J. Identification of intracellular factor XIII in human monocytes and macrophages. J Clin Invest 1985; 76: 528-34.
  • 6 Ádány R, Belkin A, Vasilevskaya T, Muszbek L. Identification of blood coagulation factor XIII in human peritoneal macrophages. Eur J Cell Biol 1985; 38: 171-3.
  • 7 Ádány R, Kappelmayer J, Muszbek L. Expression of factor XIII subunit a in different types of human monocytes and macrophages. Adv Biosci 1987; 66: 323-33.
  • 8 Ádány R, Nemes Z, Muszbek L. Characterization of factor XIII containing macrophages in lymph nodes with Hodgkin’s disease. Br J Cancer 1987; 55: 421-6.
  • 9 Ádány R, Glukhova AM, Kabakov AY, Muszbek L. Characterization of human connective tissue cells containing factor XIII subunit a. J Clin Pathol 1988; 41: 49-56.
  • 10 Ádány R, Antal M. Three different cell types can synthesize factor XIII subunit a in the human liver. Thromb Haemost 1996; 76: 74-7.
  • 11 Cohen I, Young-Bandala L, Blankenberg TA, Siefring Jr GE, BrunerLorand J. Fibrinoligase-catalyzed cross-linking of myosin from platelet and skeletal muscle. Arch Biochem Biophys 1979; 192: 100-11.
  • 12 Cohen I, Blankenberg TA, Borden D, Kahn DR, Veis A. Factor XIIIa-catalyzed cross-linking of platelet and muscle actin. Regulation by nucleotides. Biochim Biophys Acta 1980; 628: 365-75.
  • 13 Asijee GM, Muszbek L, Kappelmayer J, Polgár J, Horvth A, Sturk A. Platelet vinculin: a substrate of activated factor XIII. Biochim Biophys Acta 1988; 954: 303-8.
  • 14 Muszbek L, Ádány R, Mikkola H. Novel aspects of blood coagulation factor XIII. I. Structure distribution, activation, and function. Crit Rev Clin Lab Sci 1996; 33: 357-421.
  • 15 Ádány R. Intracellular factor XIII: Cellular distribution of factor XIII subunit a in humans. Sem Thromb Hemostas 1996; 22: 399-408.
  • 16 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680-5.
  • 17 Hodgson AJ, Penke B, Erdei A, Chubb IW, Somogyi P. Antisera to gamma-aminobutyric acid. I. Production and characterization using a new model system. J Histochem Cytochem 1985; 33: 229-39.
  • 18 Engvall E, Perlman P. Enzyme-linked immunosorbent assay (ELISA). Quantitative assay of immunoglobulin G. Immunochemistry 1971; 8: 871-4.
  • 19 Cohen PA, Kim H, Fowler DH, Gress RE, Jakobsen MK, Alexander RB, Mule JJ, Carter C, Rosenberg SA. Use of interleukin-7, interleukin-2, and interferon-gamma to propagate CD4+ T cells in culture with maintained antigen specificity. J Immunother 1993; 14: 242-52.
  • 20 Czerniecki BJ, Carter C, Rivoltini L, Koski GK, Kim HI, Weng DE, Roros JG, Hijazi YM, Xu S, Rosenberg SA, Cohen PA. Calcium ionophore-treated peripheral blood monocytes and dendritic cells rapidly display characteristics of activated dendritic cells. J Immunol 1997; 159: 3823-37.
  • 21 Belgrader P, Siegel AJ, Berezney R. A comprehensive study on the isolation and characterization of the HELA S3 nuclear matrix. J Cell Sci 1991; 98: 281-91.
  • 22 Ádány R, Kiss A, Muszbek L. Factor XIII: a marker of mono- and megakariocytopoesis. Br J Heamatol 1987; 67: 167-72.
  • 23 Ádány R, Muszbek L. Cells containing factor XIII subunit a in benign and malignant soft tissue tumours. Histopathology 1987; 11: 1341-3.
  • 24 Nemes Z, Thomázy V, Ádány R, Muszbek L. Identification of histiocytic reticulum cells by the immunohistochemical demonstration of factor XIII (F-XIIIa) in human lymph nodes. J Pathol 1986; 149: 121-32.
  • 25 Nemes Z, Ádány R, Thomázy V. Selective visualization of human dendritic reticulum cells in reactive lymphoid follicles by the immunohistochemical demonstration of the subunit A of factor XIII (F-XIIIa). Virchows Arch Cell Pathol 1987; 52: 453-66.
  • 26 Weisberg LJ, Shin DT, Conkling PR, Shuman MA. Identification of normal peripheral blood monocytes and liver as sites of synthesis of coagulation factor XIII a-chain. Blood 1987; 70: 579-82.
  • 27 Kaetsu H, Hashiguchi T, Foster D, Ichinose A. Expression and release of the a and b subunits for human coagulation factor XIII in baby hamster kidney (BHK) cells. J Biochem Tokyo 1996; 119: 961-9.
  • 28 Kradin RL, Lynch GW, Kurnick JT, Erickson M, Colvin RB, McDonagh J. Factor XIII A is synthesized and expressed on the surface of U937 cells and alveolar macrophages. Blood 1987; 69: 778-85.
  • 29 Horváth AR, Asijee GM, Muszbek L. Cytoskeletal assembly and vinculincytoskeleton interaction in different phases of the activation of bovine platelets. Cell Motil Cytoskeleton 1992; 21: 123-31.
  • 30 Davies PJ, Davies DR, Levitzki A, Maxfield FR, Milhaud P, Willingham MC, Pastan IH. Transglutaminase is essential in receptor-mediated endocytosis of alpha 2-macroglobulin and polypeptide hormones. Nature 1980; 283: 162-7.
  • 31 Aeschlimann D, Wetterwald A, Fleisch H, Paulsson M. Expression of tissue transglutaminase in skeletal tissues correlates with events of terminal differentiation of chondrocytes. J Cell Biol 1993; 120: 1461-70.
  • 32 Fésüs L, Thomázy V, Falus A. Induction and activation of tissue transglutaminase during programmed cell death. FEBS Lett 1987; 224: 104-8.
  • 33 Fésüs L, Thomázy V, Autuori F, Ceru MP, Tarcsa E, Piacentini M. Apoptotic hepatocytes become insoluble in detergents and chaotropic agents as a result of transglutaminase action. FEBS Lett 1989; 245: 150-4.
  • 34 Fésüs L, Thomázy V. Searching for the function of tissue transglutaminase: its possible involvement in the biochemical pathway of programmed cell death. Adv Exp Med Biol 1988; 231: 119-34.
  • 35 Berbers GA, Feenstra RW, van den Bos R, Hoekman WA, Bloemendal H, de Jong WW. Lens transglutaminase selects specific beta-crystallin sequences as substrate. Proc Natl Acad Sci USA 1984; 81: 7017-20.
  • 36 Ando Y, Imamura S, Owada MK, Kannagi R. Calcium-induced intracellular cross-linking of lipocortin I by tissue transglutaminase in A431 cells. Augmentation by membrane phospholipids. J Biol Chem 1991; 266: 1101-8.
  • 37 Lee KN, Maxwell MD, Patterson Jr MK, Birckbichler PJ, Conway E. Identification of transglutaminase substrates in HT29 colon cancer cells: use of 5-(biotinamido)pentylamine as a transglutaminase-specific probe. Biochim Biophys Acta 1992; 1136: 12-6.
  • 38 Takashi R. A novel actin label: a fluorescent probe at glutamine-41 and its consequences. Biochemistry 1988; 27: 938-43.
  • 39 Nemes Jr Z, Ádány R, Balázs M, Boross P, Fésüs L. Identification of cytoplasmic actin as an abundant glutaminyl substrate for tissue transglutaminase in HL-60 and U937 cells undergoing apoptosis. J Biol Chem 1997; 272: 20577-83.
  • 40 Ballestar E, Abad C, Franco L. Core histones are glutaminyl substrates for tissue transglutaminase. J Biol Chem 1996; 271: 18817-24.
  • 41 Shimizu T, Hozumi K, Horiike S, Nunomura K, Ikegami S, Takao T, Shimonishi Y. A covalently crosslinked histone. Nature 1996; 380: 32.
  • 42 Lesort M, Attanavanich K, Zhang J, Johnson GV. Distinct nuclear localization and activity of tissue transglutaminase. J Biol Chem 1998; 273: 11991-4.
  • 43 Peng X, Zhang Y, Zhang H, Graner S, Williams JF, Levitt ML, Lokshin A. Interaction of tissue transglutaminase with nuclear transport protein importin-alpha3. FEBS Lett 1999; 446: 35-9.
  • 44 Zhang J, Tucholski J, Lesort M, Jope RS, Johnson GV. Novel bimodal effects of the G-protein tissue transglutaminase on adrenoreceptor signalling. Biochem J 1999; 343: 541-9.