Molecular mechanisms of leukocyte recruitment: organ-specific mechanisms of action

Summary

Leukocyte recruitment in the microcirculation is a critical process underlying inflammatory responses in tissues. The mechanism of recruitment is summarized by the generally accepted paradigm: selectin-mediated leukocyte rolling, subsequent integrin activation, followed by integrin-mediated firm adhesion. This simple paradigm may not be able to explain the leukocyte recruitment mechanisms in some organs including the liver and brain. Recent studies suggested that these organs have their own leukocyte recruitment paradigms in acute and even chronic inflammation. The combination of unique hemo-dynamic patterns and specific structural and functional features of the vessels and endothelium in liver may dictate and select the specific patterns of leukocyte recruitment in this organ. In the brain microvasculature, where shears are high and adhesion molecule expression low, platelets may play an important role as a bridge between the leukocytes and endothelium.

Keywords

Inflammation - cellular interaction - selectins - integrins - liver - brain

• References

• 1 Cohnheim J.. Vorlesungen über allgemeine Pathologie. Berlin: August Hirschwald Verlag; 1877
• 2 Doerschuk CM. Mechanisms of leukocyte sequestration in inflamed lungs. Microcirculation 2001; 8 (02) 71-88.
• 3 Mizgerd JP. Molecular mechanisms of neutrophil recruitment elicited by bacteria in the lungs. Semin Immunol 2002; 14 (02) 123-32.
• 4 Butcher EC. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell 1991; 67: 1033-6.
• 5 Springer TA. Traffic signals of lymphocyte recirculation and leukocyte emigration: The multistep paradigm. Cell 1994; 76: 301-14.
• 6 Von Andrian UH, Chambers JD, McEvoy LM, Bargatze RF, Arfors KE, Butcher EC.. Two-step model of leukocyte-endothelial cell interaction in inflammation: distinct roles for LECAM-1 and the leukocyte β₂ integrins in vivo. . Proc Natl Acad Sci USA 1991; 88: 7538-42.
• 7 Kubes P, Kerfoot SM. Leukocyte recruitment in the microcirculation: the rolling paradigm revisited. News Physiol Sci 2001; 16: 76-80.
• 8 Johnston B, Walter UM, Issekutz AC, Issekutz TB, Anderson DC, Kubes P. Differential roles of selectins and the ₄-integrin in acute, suba-cute, and chronic leukocyte recruitment in vivo. J Immunol 1997; 159 (09) 4514-23.
• 9 Mayadas TN, Johnson RC, Rayburn H, Hynes RO, Wagner DD. Leukocyte rolling and extravasation are severely compromised in P-selectin-deficient mice. Cell 1993; 74: 541-54.
• 10 Frenette PS, Mayadas TN, Rayburn H, Hynes RO, Wagner DD. Susceptibility to infection and altered hematopoiesis in mice deficient in both P-and E-selectins. Cell 1996; 84: 563-74.
• 11 Geng JG, Bevilacqua MP, Moore KL, McIntyre TM, Prescott SM, Kim JM. et al. Rapid neutrophil adhesion to activated endothelium mediated by GMP-140. Nature 1990; 343: 757-60.
• 12 Kubes P, Kanwar S. Histamine induces leukocyte rolling in post-capillary venules: A P-selectin-mediated event. J Immunol 1994; 152: 3570-7.
• 13 Kanwar S, Johnston B, Kubes P. Leukotriene C4/D4 induces P-selectin and sialyl lewis^x-dependent alterations in leukocyte kinetics in vivo. Circ Res 1995; 77: 879-87.
• 14 Zimmerman BJ, Paulson JC, Arrhenius TS, Gaeta FCA, Granger DN. Thrombin receptor peptide-mediated leukocyte rolling in rat mesenteric venules: roles of P-selectin and sialyl Lewis X. Am J Physiol 1994; 267: H1049-H1053.
• 15 Kishimoto TK, Warnock RA, Jutila MA, Butcher EC, Lane C, Anderson DC. et al. Antibodies against human neutrophil LECAM-1 (LAM-1/Leu-8/DREG-56 antigen) and endothelial cell ELAM-1 inhibit a common CD18-independent adhesion pathway in vitro. Blood 1991; 78: 805-11.
• 16 Lo SK, Bevilacqua MB, Malik AB. E-Selectin ligands mediate tumor necrosis factor-induced neutrophil sequestration and pulmonary edema in guinea pig lungs. Circulation Research 1994; 75 (06) 955-60.
• 17 Yao L, Setiadi H, Xia L, Laszik Z, Taylor FB, McEver RP. Divergent inducible expression of P-selectin and E-selectin in mice and primates. Blood 1999; 94 (11) 3820-8.
• 18 Xia L, Sperandio M, Yago T, McDaniel JM, Cummings RD, Pearson-White S. et al. P-selectin glycoprotein ligand-1-deficient mice have impaired leukocyte tethering to E-selectin under flow. J Clin Invest 2002; 109 (07) 939-50.
• 19 Yang J, Hirata T, Croce K, Merrill-Skoloff G, Tchernychev B, Williams E. et al. Targeted gene disruption demonstrates that P-selectin glycoprotein ligand 1 (PSGL-1) is required for P-selectin-mediated but not E-selectin-mediated neutrophil rolling and migration. J Exp Med 1999; 190 (12) 1769-82.
• 20 Nolte D, Schmid P, Jager U, Botzlar A, Roesken F, Hecht R. et al. Leukocyte rolling in venules of striated muscle and skin is mediated by P-selectin, not by L-selectin. Am J Physiol 1994; 267: H1637-H1642.
• 21 Ley K, Bullard DC, Arbones ML, Bosse R, Vestweber D, Tedder TF. et al. Sequential contribution of L-and P-selectin to leukocyte rolling in vivo. J Exp Med 1995; 181 (02) 669-75.
• 22 Arbones ML, Ord DC, Ley K, Ratech H, Maynard-Curry C, Otten G. et al. Lymphocyte homing and leukocyte rolling and migration are impaired in L-selectin-deficient mice. Immunity 1994; 1: 247-60.
• 23 Kanwar S, Steeber DA, Tedder TF, Hickey MJ, Kubes P. Overlapping roles for L-selectin and P-selectin in antigen-induced immune responses in the microvasculature. J Immunol 1999; 162 (05) 2709-16.
• 24 Kubes P, Jutila M, Payne D. Therapeutic potential of inhibiting leukocyte rolling in ischemia/reperfusion. J Clin Invest 1995; 95: 2510-9.
• 25 Kanwar S, Smith CW, Kubes P. An absolute requirement for P-selectin in ischemia/reper-fusion-induced leukocyte recruitment in cremaster muscle. Microcirc 1998; 5: 281-7.
• 26 Granger DN, Benoit JN, Suzuki M, Grisham MB. Leukocyte adherence to venular endothelium during ischemia-reperfusion. Am J Physiol 1989; 257: G683-G688.
• 27 Sriramarao P, Von Andrian UH, Butcher EC, Bourdon MA, Broide DH. L-selectin and very late antigen-4 integrin promote eosinophil rolling at physiological shear rates in vivo. J Immunol 1994; 153: 4238-46.
• 28 Berlin C, Bargatze RF, Campbell JJ, Von Andrian UH, Szabo MC, Hasslen SR. et al. 4 integrins mediate lymphocyte attachment and rolling under physiologic flow. Cell 1995; 80: 413-22.
• 29 Alon R, Kassner PD, Carr MW, Finger EB, Hemler ME, Springer TA. The integrin VLA-4 supports tethering and rolling in flow on VCAM-1. J Cell Biol 1995; 128: 1243-53.
• 30 Kanwar S, Bullard DC, Hickey MJ, Smith CW, Beaudet AL, Wolitzky BA. et al. The association between ₄-integrin, P-selectin, and E-selectin in an allergic model of inflammation. J Exp Med 1997; 185 (06) 1077-87.
• 31 Johnston B, Issekutz TB, Kubes P. The 4-integrin supports leukocyte rolling and adhesion in chronically inflamed postcapillary venules in vivo. J Exp Med 1996; 181: 1995-2006.
• 32 Salmi M, Jalkanen S. VAP-1: an adhesin and an enzyme. Trends in Immunology 2001; 22 (04) 211-6.
• 33 Salmi M, Tohka S, Jalkanen S. Human vascular adhesion protein-1 (VAP-1) plays a critical role in lymphocyte-endothelial cell adhesion cascade under shear. Circ Res 2000; 86: 1245-51.
• 34 Salmi M, Yegutkin GG, Lehvonen R, Koskinen K, Salminen T, Jalkanen S. A cell surface amine oxidase directly controls lymphocyte migration. Immunity 2001; 14 (03) 265-76.
• 35 Tohka S, Laukkanen ML, Jalkanen S, Salmi M.. Vascular adhesion protein 1 (VAP-1) functions as a molecular brake during granulocyte rolling and mediates recruitment in vivo. . FASEB J 2001; 15: 373-82.
• 36 Wong J, Johnston B, Lee SS, Bullard DC, Smith CW, Beaudet AL. et al. A minimal role for selectins in the recruitment of leukocytes into the inflamed liver microvasculature. J Clin Invest 1997; 99: 2782-90.
• 37 Fox-Robichaud A, Kubes P. Molecular mechanisms of tumor necrosis factor -stimulated leukocyte recruitment into the hepatic circulation. Hepatology 2000; 31 (05) 1123-7.
• 38 Lalor PF, Shields P, Grant A, Adams DH. Recruitment of lymphocytes to the human liver. Immunol Cell Biol 2002; 80 (01) 52-64.
• 39 Wisse E, De Zanger RB, Charels K, van der Smissen P, McCuskey RS. The liver sieve: considerations concerning the structure and function of endothelial fenestrae, the sinusoidal wall and the space of Disse. Hepatology 1985; 5 (04) 683-92.
• 40 Steinhoff G, Behrend M, Schrader B, Duijvestijn AM, Wonigeit K. Expression patterns of leukocyte adhesion ligand molecules on human liver endothelia. Lack of ELAM-1 and CD52 inducibility on sinusoidal endothelia and distinct distribution of VCAM-1, ICAM-1, ICAM-2, and LFA-3. Am J Pathol 1993; 142 (02) 481-8.
• 41 Scoazec JY, Feldmann G. The cell adhesion molecules of hepatic sinusoidal endothelial cells. J Hepatol 1994; 20 (02) 296-300.
• 42 Scoazec JY, Racine L, Couvelard A, Flejou JF, Feldmann G. Endothelial cell heterogeneity in the normal human liver acinus: in situ immunohistochemical demonstration. Liver 1994; 14 (03) 113-23.
• 43 McNab G, Reeves JL, Salmi M, Hubscher S, Jalkanen S, Adams DH. Vascular adhesion protein 1 mediates binding of T cells to human hepatic endothelium. Gastroenterology 1996; 110: 522-8.
• 44 Carvalho-Tavares J, Fox-Robichaud A, Kubes P. Assessment of the mechanism of juxtacrine activation and adhesion of leukocytes in liver microcirculation. Am J Physiol 1999; 276 4 Pt 1 G828-G834.
• 45 Kubes P, Payne D, Woodman RC. Molecular mechanisms of leukocyte recruitment in postischemic liver microcirculation. Am J Physiol Gastrointest Liver Physiol 2002; 283 (01) G139-G147.
• 46 Horie Y, Wolf R, Anderson DC, Granger DN. Hepatic leukostasis and hypoxic stress in adhesion molecule-deficient mice after gut ischemia/reperfusion. J Clin Invest 1997; 99 (04) 781-8.
• 47 Li Y, Muruve DA, Collins RG, Lee SS, Kubes P. The role of selectins and integrins in adenovirus vector-induced neutrophil recruitment to the liver. Eur J Immunol 2002; 32 (12) 3443-52.
• 48 Farhood A, McGuire GM, Manning AM, Miyasaka M, Smith CW, Jaeschke H. Intercellular adhesion molecule 1 (ICAM-1) expression and its role in neutrophil-induced ischemia-reperfusion injury in rat liver. J Leuk Biol 1995; 57: 368-74.
• 49 Essani NA, Fisher MA, Farhood A, Manning AM, Smith CW, Jaeschke H. Cytokine-induced upregulation of hepatic intercellular adhesion molecule-1 messenger RNA expression and its role in the pathophysiology of murine endotoxin shock and acute liver failure. Hepatology 1995; 21: 1632-9.
• 50 Jaeschke H, Farhood A, Bautista AP, Spolarics Z, Spitzer JJ, Smith CW. Functional inactivation of neutrophils with a Mac-1 (CD11b/ CD18) monoclonal antibody protects against ischemia-reperfusion injury in rat liver. Hepatology 1993; 17: 915-23.
• 51 Jaeschke H. Cellular adhesion molecules: regulation and functional significance in the pathogenesis of liver diseases. Am J Physiol 1997; 273: G602-G611.
• 52 Jaeschke H, Farhood A, Fisher MA, Smith CW. Sequestration of neutrophils in the hepatic vasculature during endotoxemia is independent of 2 integrins and intercellular adhesion molecule-1. Shock 1996; 6 (05) 351-6.
• 53 Carvalho-Tavares J, Hickey MJ, Hutchison J, Michaud J, Sutcliffe IT, Kubes P. A role for platelets and endothelial selectins in tumor necrosis factor-induced leukocyte recruitment in the brain microvasculature. Circ Res 2000; 87 (12) 1141-8.
• 54 Barkalow FJ, Goodman MJ, Gerritsen ME, Mayadas TN. Brain endothelium lack one of two pathways of P-selectin-mediated neutrophil adhesion. Blood 1996; 88 (12) 4585-93.
• 55 Yong T, Zheng MQ, Linthicum DS. Local histamine release increases leukocyte rolling in the cerebral microcirculation of the mouse. Brain Injury 1997; 11 (10) 765-74.
• 56 Grady MS, Cody Jr. RF, Maris DO, McCall TD, Seckin H, Sharar SR. et al. P-selectin blockade following fluid-percussion injury: behavioral and immunochemical sequelae. J Neurotrauma 1999; 16 (01) 13-25.
• 57 Suzuki H, Hayashi T, Tojo SJ, Kitagawa H, Kimura K, Mizugaki M. et al. Anti-P-selectin antibody attenuates rat brain ischemic injury. Neurosci Lett 1999; 265 (03) 163-6.
• 58 Connolly Jr. ES, Winfree CJ, Prestigiacomo CJ, Kim SC, Choudhri TF, Hoh BL. et al. Exacerbation of cerebral injury in mice that express the P-selectin gene. Identification of P-selectin blockade as a new target for the treatment of stroke. Circ Res 1997; 81: 304-10.
• 59 Washington R, Burton J, Todd III RF, Newman W, Dragovic L, Dore-Duffy P. Expression of immunologically relevant endothelial cell activation antigens on isolated central nervous system microvessels from patients with multiple sclerosis. Ann Neurol 1994; 35 (01) 89-97.
• 60 Lee SJ, Benveniste EN. Adhesion molecule expression and regulation on cells of the central nervous system. J Neuroimmunol 1999; 98: 77-88.
• 61 Tang T, Frenette PS, Hynes RO, Wagner DD, Mayadas TN. Cytokine-induced meningitis is dramatically attenuated in mice deficient in endothelial selectins. J Clin Invest 1996; 97 (11) 2485-90.
• 62 Andersson PB, Perry VH, Gordon S. Intracerebral injection of proinflammatory cytokines or leukocyte chemotaxins induces minimal myelomonocytic cell recruitment to the parenchyma of the central nervous system. J Exp Med 1992; 176: 255-9.
• 63 Engelhardt B, Vestweber D, Hallmann R, Schulz R. E- and P-selectin are not involved in the recruitment of inflammatory cells across the blood-brain barrier in experimental autoimmune encephalomyelitis. Blood 1997; 90 (11) 4459-72.
• 64 Crone C. The permeability of capillaries in various organs as determined by use of the “indicator diffusion” method. Acta Physiol Scand 1963; 58: 292-305.
• 65 Labow MA, Norton CR, Rumberger JM, Lombard-Gillooly KM, Shuster DJ, Hubbard J. et al. Characterization of E-selectin-deficient mice: demonstration of overlapping function of the endothelial selectins. Immunity 1994; 1: 709-20.
• 66 Kanda T, Yamawaki M, Ariga T, Yu RK. Interleukin 1 up-regulates the expression of sulfoglucuronosyl paragloboside, a ligand for L-selectin, in brain microvascular endothelial cells. Proc Natl Acad Sci USA 1995; 92 (17) 7897-901.
• 67 Bednar MM, Gross CE, Russel SR, Fuller SP, Ellenberger CL, Schindler E. et al. Humani-zed anti-L-selectin monoclonal antibody DREG200 therapy in acute thromboembolic stroke. Neurol Res 1998; 20: 403-8.
• 68 Kuijper PHM, Torres HIG, van der Linden JAM, Lammers JWJ, Sixma JJ, Koenderman L. et al. Platelet-dependent primary hemostasis promotes selectin- and integrin-mediated neutrophil adhesion to damaged endothelium under flow conditions. Blood 1996; 87 (08) 3271-81.
• 69 Ostrovsky L, King AJ, Bond S, Mitchell Niu X-FD, Kubes P. A juxtacrine mechanism for neutrophil adhesion on platelets involves platelet-activating factor and a selectin-dependent activation process. Blood 1998; 91: 3028-36.
• 70 Bombeli T, Schwartz BR, Harlan JM. Adhesion of activated platelets to endothelial cells: evidence for a GPIIbIIIa-dependent bridging mechanism and novel roles for endothelial intercellular adhesion molecule 1 (ICAM-1), _{v 3} integrin, and GPIb. J Exp Med 1998; 187 (03) 329-39.
• 71 Romo MG, Dong J-F, Schade AJ, Gardiner EE, Kansas GS, Li CQ. et al. The glycoprotein Ib-IX-V complex is a platelet conterrecep-tor for P-selectin. J Exp Med 1999; 190: 803-13.
• 72 Utley JR. Pathophysiology of cardiopulmonary bypass: current issues. J Card Surg 1990; 5 (03) 177-89.
• 73 de Gaetano G, Cerletti C. Aspirin, platelets and prevention of vascular disease. J Lipid Mediat 1989; 1 (05) 289-96.
• 74 Joseph R, Han E, Tsering C, Grunfeld S, Welch KM. Platelet activity and stroke severity. J Neurol Sci 1992; 108 (01) 1-6.
• 75 Zhang RL, Chopp M, Li Y, Zaloga C, Jiang N, Jones ML. et al. Anti-ICAM-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in the rat. Neurology 1994; 44 (09) 1747-51.
• 76 Sobel RA, Mitchell ME, Fondren G. Intercellular adhesion molecule-1 (ICAM-1) in cellular immune reactions in the human central nervous system. Am J Pathol 1990; 136 (06) 1309-16.
• 77 Bowes MP, Zivin JA, Rothlein R. Monoclonal antibody to the ICAM-1 adhesion site reduces neurological damage in a rabbit cerebral embolism stroke model. Exp Neurol 1993; 119 (02) 215-9.
• 78 Granger DN. Ischemia-reperfusion: mechanisms of microvascular dysfunction and the influence of risk factors for cardiovascular disease. Microcirculation 1999; 6 (03) 167-78.
• 79 Connolly Jr. ES, Winfree CJ, Springer TA, Naka Y, Liao H, Yan SD. et al. Cerebral protection in homozygous null ICAM-1 mice after middle cerebral artery occlusion. Role of neutrophil adhesion in the pathogenesis of stroke. J Clin Invest 1996; 97 (01) 209-16.
• 80 Luscinskas FW, Ma S, Nusrat A, Parkos CA, Shaw SK. The role of endothelial cell lateral junctions during leukocyte trafficking. Immunol Rev 2002; 186: 57-67.
• 81 Del Maschio A, De Luigi A, Martin-Padura I, Brockhaus M, Bartfai T, Fruscella P. et al. Leukocyte recruitment in the cerebrospinal fluid of mice with experimental meningitis is inhibited by an antibody to junctional adhesion molecule (JAM). J Exp Med 1999; 190 (09) 1351-6.
• 82 Ostermann G, Weber KS, Zernecke A, Schroder A, Weber C. JAM-1 is a ligand of the 2-integrin LFA-1 involved in transendothelial migration of leukocytes. Nat Immunol 2002; 3 (02) 151-8.
• 83 Kent SJ, Karlik SJ, Cannon C, Hines DK, Yednock TA, Fritz LC. et al. A monoclonal antibody to 4 integrin suppresses and reverses active experimental allergic encephalomyelitis. J Neuroimmunol 1995; 58: 1-10.
• 84 Kerfoot SM, Kubes P. Overlapping roles of P-selectin and 4 integrin to recruit leukocytes to the central nervous system in experimental autoimmune encephalomyelitis. J Immunol 2002; 169 (02) 1000-6.
• 85 Keszthelyi E, Karlik S, Hyduk S, Rice GP, Gordon G, Yednock TA. et al. Evidence for a prolonged role of ₄ integrin throughout active experimental allergic encephalomyelitis. Neurology 1996; 47: 1053-9.
• 86 Yednock TA, Cannon C, Fritz LC, Sanchez-Madrid F, Steinman L, Karin N. Prevention of experimental autoimmune encephalomyelitis by antibodies against 4 1 integrin. Nature 1992; 356: 63-6.