The Role of β2-Leukocyte Integrins In Vivo

  • S. R. Sharar
  • N. B. Vedder
  • W. J. Mileski
  • C. L. Rice
  • J. M. Harlan
  • R. K. Winn


The acute inflammatory response is characterized by the destructive activity of leukocytes against foreign pathogens and/or host tissue. In the event of bacterial invasion, leukocytes are directed to the site of infection by the release of soluble chemotactic agents. Leukocyte localization to the appropriate endothelium results from adherence to endothelial cells, followed by subsequent migration to the site of infection. Leukocytes phagocytose the invading bacteria and release toxic products (e.g., oxygen radicals, proteases) into phagosomes to act against the invading pathogens to protect the host. In noninfectious conditions such as ischemia-reperfusion injury, leukocytes may release these same substances into surrounding tissue causing destruction to the host. This process can occur when activated leukocytes becoming adherent to endothelial cells form a protected microenvironment at the cell-cell interface. This region is relatively inaccessible to plasma inhibitors of toxic leukocyte products (e.g., antioxidants and antiproteases), resulting in direct endothelial cell injury by these leukocyte products, loss of vascular integrity, tissue edema, and thrombosis.


Bacterial Meningitis Hemorrhagic Shock Tissue Edema Neutrophil Adherence Shed Blood 
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.
    Larson RS, Springer TA (1990) Structure and function of leukocyte integrins. Immunol Rev 114:181–217PubMedCrossRefGoogle Scholar
  2. 2.
    Albelda SM, Buck CA (1990) Integrins and other cell adhesion molecules. FASEB J 4:2868–2880PubMedGoogle Scholar
  3. 3.
    Patarroyo M, Beatty PG, Serhan CN, Gahmberg CG (1985) Identification of a cell-surface glycoprotein mediating adhesion in human granulocytes. Scand J Immunol 22:619–623PubMedCrossRefGoogle Scholar
  4. 4.
    Diener AM, Beatty PG, Ochs HD, Harlan JM (1985) The role of neutrophil membrane glycoprotein 150 (GP-150) in neutrophil-mediated endothelial cell injury in vitro. J Immunol 135:537–543PubMedGoogle Scholar
  5. 5.
    Harlan JM, Schwartz BR, Reidy MA, Schwartz SM, Ochs HD, Harker LA (1985) Activated neutrophils disrupt endothelial monolayer integrity by an oxygen radical-independent mechanism. Lab Invest 52:141–150PubMedGoogle Scholar
  6. 6.
    Arfors KE, Lundberg C, Lindbom L, Lunderg K, Beatty PG, Harlan JM (1987) a monoclonal antibody to the membrane glycoprotein complex CD18 inhibits polymorphonuclear leukocyte accumulation and plasma leakage in vivo. Blood 69:338–340PubMedGoogle Scholar
  7. 7.
    Carlos TM, Harlan JM (1990) Membrane proteins involved in phagocyte adherence to endothelium. Immunol Rev 114:5–28PubMedCrossRefGoogle Scholar
  8. 8.
    Hernandez LA, Grisham MB, Twohig B, Arfors KE, Harlan JM, Granger DN (1987) Role of neutrophils in ischemia-reperfusion-induced microvascular injury. Am J Physiol 253:H699–H703PubMedGoogle Scholar
  9. 9.
    Simpson PJ, Todd RF III, Fantone JC, Mickelson JK, Griffin JD, Lucchesi BR (1988) Reduction of experimental canine myocardial reperfusion injury by a monoclonal antibody (anti-Mol, anti-CD11b) that inhibits leukocyte adhesion. J Clin Invest 81:624–629PubMedCrossRefGoogle Scholar
  10. 10.
    Vedder NB, Winn RK, Rice CL, Chi EY, Arfors KE, Harlan JM (19988) A monoclonal antibody to the adherence promoting leukocyte glycoprotein CD18 reduces organ injury and improves survival from hemorrhagic shock and resuscitation in rabbits. J Clin Invest 81:939–944CrossRefGoogle Scholar
  11. 11.
    Vedder NB, Fouty BW, Winn RK, Harlan JM, Rice CL (1989) Role of neutrophils in generalized reperfusion injury associated with resuscitation from shock. Surgery 106:509–516PubMedGoogle Scholar
  12. 12.
    Vedder NB, Winn RK, Rice CL, Chi EY, Arfors KE, Harlan JM (1990) Inhibition of leukocyte adherence by anti-CD18 monoclonal antibody attenuates reperfusion injury in the rabbit ear. Proc Natl Acad Sci USA 87:2643–2646PubMedCrossRefGoogle Scholar
  13. 13.
    Mileski WJ, Winn RK, Vedder NB, Pohlaman TH, Harlan JM, Rice CL (1990) Inhibition of CD18-dependent neutrophil adherence reduces organ injury after hemorrhagic shock in primates. Surgery 108:206–212PubMedGoogle Scholar
  14. 14.
    Tuomanen EI, Saukkonen Kirsi, Sande S, Cioffe C, Wright SD (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 170:959–968PubMedCrossRefGoogle Scholar
  15. 15.
    Thornton MA, Winn R, Alpers CE, Zager RA (1989) An evaluation of the neutrophil as a mediator of in vivo renal ischemic-reperfusion injury. Am J Pathol 135:509–515PubMedGoogle Scholar
  16. 16.
    Faist E, Bauer AE, Dittmer H, Heberer G (1983) Multiple organ failure in polytrauma patients. J Trauma 23:775–787PubMedCrossRefGoogle Scholar
  17. 17.
    Goris RJA, te Boekhorst TPA, Nuytinck JKS, Gimbrere JSF (1985) Multiple organ failure. Generalized autodestructive inflammation? Arch Surg 120:1109–1115PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag, Berlin Heidelberg 1993

Authors and Affiliations

  • S. R. Sharar
    • 1
  • N. B. Vedder
    • 1
  • W. J. Mileski
    • 1
  • C. L. Rice
    • 1
  • J. M. Harlan
    • 1
  • R. K. Winn
    • 1
  1. 1.Departments of Anesthesiology, Surgery, Medicine, and Physiology-BiophysicsUniversity of Washington, Harborview Medical CenterSeattleUSA

Personalised recommendations