Lung Inflammation and Adhesion Molecules

  • Michael S. Mulligan
  • Peter A. Ward
Part of the New Horizons in Therapeutics book series (NHTH)

Abstract

Adhesion molecules have been shown to be important in inducing inflammatory responses in experimental animals. The topic has recently been the subject of a fairly extensive review (Harlan and Liu, 1992). Adhesion molecules on endothelial cells and leukocytes are diverse, and can be divided into two groups: those that are constitutively expressed, and those that are inducible after endothelial cell contact with appropriate stimuli. Table I presents some of the adhesion molecules of endothelial cells and neutrophils that are most important in the inflammatory response. In this context, the chief difference between endothelial cells and leukocytes is that adhesion molecules are generally not constitutively expressed on the former, whereas they are on the latter. ICAM-1 and -2 are normally constitutively expressed in small amounts on endothelial cells. When endothelial cells are stimulated with TNFα, IL-1, or endotoxin, gene activation occurs, and ICAM expression is slowly but steadily increased over the next 12 hr. Also triggered is the gene controlling expression of E-selctin (ELAM-1), with maximal expression developing in about 4 hr. P-selectin is an exception to the requirement for protein synthesis; this glycoprotein is stored in the Weibel-Palade granules of endothelial cells (and in the alpha granules of platelets), and can be rapidly translocated (in 5-10 min) to the endothelial cell surface after the addition of histamine or thrombin. The most recently described adhesionpromoting molecule of the endothelial cell is Gly-CAM-1, a heavily glycosylated protein which, unlike the other adhesion molecules, has no transmembranespanning segment and appears to be entirely extracellular, embedded in the glycocalyx of the endothelial cells (Lasky et al., 1992). VCAM-1 is another adhesion-promoting molecule of endothelial cells. This glycoprotein is not normally expressed; it appears on the cell surface approximately 4 hr after stimulation, with expression being retained for the next 12-18 hr. “Counterreceptors” for these adhesion molecules are diverse (Table I). In the case of ICAM-1 and -2, the complementary reactive molecules on leukocytes are the β2 integrins (LFA-1 and Mac-1, see below). E- and P-selectin react with leukocytic lectins, which are Oligosaccharides of the structure sialyl Lewisx and sialyl Lewisa (reviewed by Harlan and Liu, 1992). Gly-CAM-l appears to be the lectin-containing molecule that is reactive with leukocytic L-selectin (see below).

Keywords

Permeability Histamine Neutropenia Integrin Catalase 

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References

  1. Beckman, J. S., Beckman, T. W., Chen, J., Marshall, P. A., and Freeman, B. A., 1990, Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and Superoxide, Proc. Natl. Acad. Sci. USA 87:1620–1624.PubMedCrossRefGoogle Scholar
  2. Craddock, P. R., Fehr, J., Dalmasso, A. P., Brigham, K. L., and Jacob, H. S., 1977, Hemodialysis leukopenia. Pulmonary vascular leukostasis resulting from complement activation by dialyzer cellophane membranes, J. Clin. Invest. 59:879–888.PubMedCrossRefGoogle Scholar
  3. Gresham, H. D., Graham, I. L., Anderson, D. C., and Brown, E. J., 1991, Leukocyte adhesiondeficient neutrophils fail to amplify phagocytic function in response to stimulation: Evidence for CD11b/CD18-dependent and-independent mechanisms of phagocytosis, J. Clin. Invest. 88:588–597.PubMedCrossRefGoogle Scholar
  4. Harlan, J. M., and Liu, D. Y. (eds.), 1992, Adhesion: Its Role in Inflammatory Disease, Freeman, San Francisco.Google Scholar
  5. Issekutz, T. B., and Wykretowicz, A., 1991, Effect of a new monoclonal antibody, TA-2, that inhibits lymphocyte adherence to cytokine stimulated endothelium in the rat, J. Immunol. 147:109–116.PubMedGoogle Scholar
  6. Johnson, K. J., and Ward, P. A., 1974, Acute immunologic pulmonary alveolitis, J. Clin. Invest. 54:349–357.PubMedCrossRefGoogle Scholar
  7. Johnson, K. J., and Ward, P. A., 1981, Role of oxygen metabolites in immune complex injury of lung, J. Immunol. 126:2365–2369.PubMedGoogle Scholar
  8. Johnson, K. J., Wilson, B. S., Till, G. O., and Ward, P. A., 1984, Acute lung injury in the rat caused by immunoglobulin A immune complexes, J. Clin. Invest. 74:358–359.PubMedCrossRefGoogle Scholar
  9. Johnson, K. J., Ward, P. A., Kunkel, R. G., and Wilson, B. S., 1986, Mediation of IgA induced lung injury in the rat: Role of macrophages and reactive oxygen products, Lab. Invest. 54:499–506.PubMedGoogle Scholar
  10. Jutila, M. A., Rott, L., Berg, E. L., and Butcher, E. C., 1989, Function and regulation of the neutrophil MEL-14 antigen in vivo: Comparison with LFA-1 and MAC-1, J. Immunol. 143:3318–3324.PubMedGoogle Scholar
  11. Lasky, L. A., Singer, M. S., Dowbenko, D., Imai, Y., Henzel, W. J., Grimley, C., Fennie, C., Gillett, N., Watson, S. W., and Rosen, S. D., 1992, An endothelial ligand for L-selectin is a novel mucin-like molecule, Cell 69:927–938.PubMedCrossRefGoogle Scholar
  12. Mulligan, M. S., and Ward, P. A., 1992, Immune complex-induced lung and dermal vascular injury: Differing requirements for TNFα and IL-1, J. Immunol. 145:331–339.Google Scholar
  13. Mulligan, M. S., Hevel, J. M., Marietta, M. A., and Ward, P. A., 1991a, Tissue injury caused by deposition of immune complexes is L-arginine dependent, Proc. Natl. Acad. Sci. USA 88:6338–6342.PubMedCrossRefGoogle Scholar
  14. Mulligan, M. S., Varani, J., Dame, M. K., Lane, C. L., Smith, C. W., Anderson, D. C., and Ward, P. A., 1991b, Role of ELAM-1 in neutrophil-mediated lung injury in rats, J. Clin. Invest. 88:1396–1406.PubMedCrossRefGoogle Scholar
  15. Mulligan, M. S., Warren, J. S., Smith, C. W., Anderson, D. C., Yeh, C. G., Rudolph, A. R., and Ward, P. A., 1992a, Lung injury after deposition of IgA immune complexes: Requirements for CD18 and L-arginine, J. Immunol. 148:3086–3092.PubMedGoogle Scholar
  16. Mulligan, M. S., Varani, J., Warren, J. S., Till, G. O., Smith, C. W., Anderson, D. C., Todd, R. F., III, and Ward, P. A., 1992b, Roles of β2 integrins of rat neutrophils in complement-and oxygen radical-mediated acute inflammatory injury, J. Immunol. 148:1847–1857.PubMedGoogle Scholar
  17. Mulligan, M. S., Polley, M. J., Bayer, R. J., Nunn, M. F., Paulson, J. C., and Ward, P. A., 1992c, Neutrophil-dependent acute lung injury: Requirement for P-selectin (GMP-140), J. Clin. Invest. 90:1600–1607.PubMedCrossRefGoogle Scholar
  18. Mulligan, M. S., Smith, C. W., Anderson, D. C., Todd, R. F. III, Miyasaka, M., Tamatani, T., Issekutz, T. B., and Ward, P. A., 1993a, Role of leukocyte adhesion molecules in complementinduced lung injury, J. Immunol. 150:2401–2406.PubMedGoogle Scholar
  19. Mulligan, M. S., Wilson, G. P., Todd, R. F. III, Smith, C. W., Anderson, D. C., Varani, J., Issekutz, T. B., Miyasaka, M., Tamatani, T., Rusche, J. R., Vaporciyan, A. A., and Ward, P. A., 1993b, Role of β1, β2 integrins and ICAM-1 in lung injury following deposition of IsG and IsA immune complexes, J. Immunol. 150:2407–2417.PubMedGoogle Scholar
  20. Nathan, C. F., 1987, Neutrophil activation on biological surfaces: Massive secretion of hydrogen peroxide in response to products of macrophages and lymphocytes, J. Clin. Invest. 80:1550–1560.PubMedCrossRefGoogle Scholar
  21. Nathan, C. F., 1989, Respiratory burst in adherent neutrophils: Triggering by colony-stimulating factors CSF-GM and CSF-G, Blood 73:301–306.PubMedGoogle Scholar
  22. Shappell, S. B., Toman, C., Anderson, D. C., Taylor, A. A., Entman, M. L., and Smith, C. W., 1990, Mac-1 (CD11b/CD18) mediates adherence-dependent hydrogen peroxide production by human and canine neutrophils, J. Immunol 144:2702–2711.PubMedGoogle Scholar
  23. Smith, C. W., Kishimoto, T. K., Abbassi, O., Hughes, B., Rothlein, R., McIntire, L. V., Butcher, E., and Anderson, D. C., 1991, Chemotactic factors regulate lectin adhesion molecule 1 (LECAM-1)-dependent neutrophil adhesion to cytokine-stimulated endothelial cells in vitro, J. Clin. Invest. 87:609–618.PubMedCrossRefGoogle Scholar
  24. Till, G. O., Johnson, K. J., Kunkel, R., and Ward, P. A., 1982, Intravascular activation of complement and acute lung injury. Dependency on neutrophils and toxic oxygen metabolites. J. Clin. Invest. 69:1126–1135.PubMedCrossRefGoogle Scholar
  25. Ward, P. A., Till, G. O., Kunkel, R., and Beauchamp, C., 1983, Evidence for role of hydroxyl radical in complement and neutrophil-dependent tissue injury, J. Clin. Invest. 72:789–801.PubMedCrossRefGoogle Scholar
  26. Warren, J. S., 1991, Intrapulmonary interleukin-1 mediates acute immune complex alveolitis in the rat, Biochem. Biophys. Res. Commun. 175:604–610.PubMedCrossRefGoogle Scholar
  27. Warren, J. S., Yabroff, K. B., Remick, D. G., Kunkel, S. L., Chensue, S. W., Kunkel, R. G., Johnson, K.J., and Ward, P. A., 1989, Tumor necrosis factor participates in the pathogenesis of acute immune complex alveolitis in the rat, J. Clin. Invest. 84:1873–1882.PubMedCrossRefGoogle Scholar
  28. Warren, J. S., Barton, P. A., Mandel, M., and Matrosic, K., 1990, Intrapulmonary tumor necrosis factor triggers local platelet-activating factor production in rat immune complex alveolitis, Lab. Invest. 63:746–754.PubMedGoogle Scholar
  29. Warren, J. S., Barton, P. A., and Jones, M. L., 1991, Contrasting roles for tumor necrosis factor in the pathogenesis of IgG and IgA immune complex lung injury, Am. J. Pathol. 138:581–590.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Michael S. Mulligan
    • 1
  • Peter A. Ward
    • 1
  1. 1.Department of PathologyThe University of MichiganAnn ArborUSA

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