Leukocyte-Mediated Endothelial Injury

  • Robert K. Winn
  • Charles L. Rice
  • Nicholas B. Vedder
  • William J. Mileski
  • John M. Harlan


The inflammatory response is characterized by leukocyte adherence to the vessel wall and subsequent infiltration of tissue by emigrated leukocytes.1 Leukocytes contain or are capable of producing a number of products that can potentially cause cell injury or modify cell function (reviewed in Ref. 2). Consequently, many investigators have proposed a causal relationship between leukocyte accumulation at sites of inflammation or immune reaction and associated vascular and tissue injury. Leukocyte-mediated injury of vascular endothelium as an “innocent bystander” has been implicated in the pathogenesis of a wide variety of clinical disorders some of which are listed in Table 1.


Reperfusion Injury Vascular Injury Hemorrhagic Shock Allograft Rejection Leukocyte Adherence 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Grant, L., 1973, The sticking and emigration of white blood cells in inflammation, in: The Inflammatory Process, Volume 2 (B. Zweifach, L. Grant, and L. McCluskey, eds.), Academic Press, New York, pp. 205–249.Google Scholar
  2. 2.
    Harlan, J. M., 1987, Consequences of leukocyte-vessel wall interactions in inflammatory and immune reactions, Semin. Thromb. Hemostasis 13:434–444.CrossRefGoogle Scholar
  3. 3.
    Tate, R. M., and Repine, J. E., 1983, Neutrophils and the adult respiratory distress syndrome, Am. Rev. Respir. Dis. 128:552–559.PubMedGoogle Scholar
  4. 4.
    Harlan, J. M., 1987, Neutrophil-mediated vascular injury, Acta Med. Scand. Suppl. 715:123–129.PubMedGoogle Scholar
  5. 5.
    Gimbrone, M. A., Jr., Obin, M. S., Brock, A. F., Luis, E. A., Hass, P. E., Hebert, C. A., Yip, Y. K., Leung, D. W., Lowe, D. G., Kohr, W. J., Darbonne, W. C., Bechtol, K. B., and Baker, J. B., 1989, Endothelial interleukin-8: A novel inhibitor of leukocyte-endothelial interactions, Science 246:1601–1603.PubMedCrossRefGoogle Scholar
  6. 6.
    Gamble, J. R., and Vadas, M. A., 1988, Endothelial adhesiveness for blood neutrophils is inhibited by transforming growth factor-β, Science 242:97–99.PubMedCrossRefGoogle Scholar
  7. 7.
    Sacks, T., Moldow, C. F., Craddock, P. R., Bowers, T. K., and Jacob, H. S., 1978, Oxygen radicals mediate endothelial cell damage by complement-stimulated granulocytes, J. Clin. Invest. 61:1161–1167.PubMedCrossRefGoogle Scholar
  8. 8.
    Shasby, D. M., Shasby, S. S., and Peach, M. H., 1983, Granulocytes and phorbol myristate acetate increase permeability to albumin of cultured endothelial monolayers and isolated perfused lungs. Role of oxygen radicals and granulocyte adherence, Am. Rev. Respir. Dis. 127:72–76.PubMedGoogle Scholar
  9. 9.
    Wallis, W. J., Hickstein, D. D., Schwartz, B. R., June, C. H., Ochs, H. D., Beatty, P. G., Klebanoff, S. J., and Harlan, J. M., 1986, Monoclonal antibody-defined functional epitopes on the adhesion-promoting glycoprotein complex (CDw18) of human neutrophils, Blood 67:1007–1013.PubMedGoogle Scholar
  10. 10.
    Arfors, K.-E., Lundberg, C., Lindbom, L., Lundberg, K., Beatty, P. G., and Harlan, J. M., 1987, A monoclonal antibody to the membrane glycoprotein complex CD18 inhibits polymorphonuclear leukocyte accumulation and plasma leakage in vivo, Blood 69:338–340.Google Scholar
  11. 11.
    Price, T. H., Beatty, P. G., and Corpuz, S. R., 1987, In vivo inhibition of neutrophil function in the rabbit using monoclonal antibody to CD18, J. Immunol. 139:4174–4177.PubMedGoogle Scholar
  12. 12.
    Rosen, H., and Gordon, S., 1987, Monoclonal antibody to the murine type 3 complement receptor inhibits adhesion of myelomonocytic cells in vitro and inflammatory cell recruitment in vivo, J. Exp. Med. 166:1685–1701.CrossRefGoogle Scholar
  13. 13.
    Tuomanen, E. I., Saukkonen, K., Sande, S., Cioffe, C., and Wright, S. D., 1989, Reduction of inflammation, tissue damage, and mortality in bacterial meningitis in rabbits treated with monoclonal antibodies against adhesion-promoting receptors of leukocytes, J. Exp. Med. 170:959–968.PubMedCrossRefGoogle Scholar
  14. 14.
    Diener, A. M., Beatty, P. G., Ochs, H. D., and Harlan, J. M., 1985, The role of neutrophil membrane glycoprotein 150 (GP-150) in neutrophil-mediated endothelial cell injury in vitro, J. Immunol. 135:537–543.Google Scholar
  15. 15.
    Hernandez, L. A., Grisham, M. B., Twohig, B., Arfors, K.-E., Harlan, J. M., and Granger, D. N., 1987, Role of neutrophils in ischemia-reperfusion-induced microvascular injury, Am. J. Physiol. 253:H699–H703.Google Scholar
  16. 16.
    Beatty, P. G., Ledbetter, J. A., Martin, P. J., Price, T. H., and Hansen, J. A., 1983, Definition of a common leukocyte cell-surface antigen (Lp 95–150) associated with diverse cell-mediated immune functions, J. Immunol. 131:2913–2918.PubMedGoogle Scholar
  17. 17.
    Petrone, W. F., English, D. K., Wong, K., and McCord, J. M., 1980, Free radicals and inflammation: Superoxide-dependent activation of a neutrophil chemotactic factor in plasma, Proc. Natl. Acad. Sci. USA 77:1159–1163.PubMedCrossRefGoogle Scholar
  18. 18.
    Suzuki, M., Inauen, W., Kvietys, P. R., Grisham, M. B., Meininger, C., Schelling, C. M., Granger, H. J., and Granger, D. N., 1989, Superoxide mediates reperfusion-induced leukocyte- endothelial cell interactions, Am. J. Physiol. 257:H1740–H1745.Google Scholar
  19. 19.
    Vedder, N. B., Fouty, B. W., Winn, R. K., Harlan, J. M., and Rice, C. L., 1989, Role of neutrophils in generalized reperfusion injury associated with resuscitation from shock, Surgery 106:509–516.PubMedGoogle Scholar
  20. 20.
    Mileski, W. J., Winn, R. K., Pohlman, T. H., Vedder, N. B., Harlan, J. M., and Rice, C. L., 1990, Inhibition of CD18-dependent neutrophil adherence reduces organ injury after hemorrhagic shock in primates, Surgery 108:206–212.PubMedGoogle Scholar
  21. 21.
    Vedder, N. B., Winn, R. K., Rice, C. L., Chi, E. Y., Arfors, K.-E., and Harlan, J. M., 1990, Inhibition of leukocyte adherence by anti-CD18 monoclonal antibody attenuates reperfusion injury in the rabbit ear, Proc. Natl. Acad. Sci. USA 87:2643–2646.PubMedCrossRefGoogle Scholar
  22. 22.
    Mileski, W., Winn, R., Harlan, J., Heimbach, D., and Rice, C., 1990, Inhibition of neutrophil (PMN) adherence with monoclonal antibody 60.3 reduces tissue loss following frostbite, Proc. Amer. Burn Assoc. 22:164.Google Scholar
  23. 23.
    Dutka, A. J., Kochanek, P. M., and Hallenbeck, J. M., 1989, Influence of granulocytopenia on canine cerebral ischemia induced by air embolism, Stroke 20:390–395.PubMedCrossRefGoogle Scholar
  24. 24.
    Simpson, P. J., Todd, R. F., III., Fantone, J. C., Mickelson, J. K., Griffin, J. D., and Lucchesi, B. R., 1988, Reduction of experimental canine myocardial reperfusion injury by a monoclonal antibody (anti-Mol, anti-CD11b) that inhibits leukocyte adhesion, J. Clin. Invest. 81:624–629.PubMedCrossRefGoogle Scholar
  25. 25.
    Thorton, M. A., Winn, R., Alpers, C. E., and Zager, R. A., 1989, An evaluation of the neutrophil as a mediator of in vivo renal ischemic-reperfusion injury, Am. J. Pathol. 135:509–515.Google Scholar
  26. 26.
    Cosimi, A. B., Conti, D., Delmonico, F. L., Preffer, F. I., Wee, S.-L., Rothlein, R., Faanes, R., and Colvin, R. B., 1990, In vivo effects of monoclonal antibody to ICAM-1 (CD54) in nonhuman primates with renal allografts, J. Immunol. 144:4604–4612.PubMedGoogle Scholar
  27. 27.
    Mileski, W. J., Winn, R. K., Harlan, J. M., and Rice, C. L., 1991, Transient inhibition of neutrophil adherence with the CD18 monoclonal antibody (MAb 60.3) does not increase mortality in abdominal sepsis, Surgery 109:497–501.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Robert K. Winn
    • 1
  • Charles L. Rice
    • 2
  • Nicholas B. Vedder
    • 2
  • William J. Mileski
    • 2
  • John M. Harlan
    • 3
  1. 1.Departments of Surgery and Physiology-BiophysicsUniversity of WashingtonSeattleUSA
  2. 2.Department of SurgeryUniversity of WashingtonSeattleUSA
  3. 3.Department of MedicineUniversity of WashingtonSeattleUSA

Personalised recommendations