Neutrophils and neutrophil-endothelial cell adhesion in adult respiratory distress syndrome.
The neutrophil has been implicated as a pivotal player in the pathogenesis of adult respiratory distress syndrome (ARDS) and multiple organ failure. An important first step in the process of neutrophil-mediated organ injury involves the binding of neutrophils to endothelial cells. This process is largely regulated by complementary adhesion molecules, some of which are present constitutively on the cell surface and others that can be up-regulated in response to chemotactic and proinflammatory stimuli. Several different adhesion molecules have been described. The leukocyte integrins consist of a common beta 2 chain (CD18) covalently linked to one of three different alpha chains (CD11a, CD11b, CD11c). CD11a/CD18 is expressed on all leukocytes, whereas CD11b/CD18 and CD11c/CD18 are restricted to cells of myeloid origin. CD11b/CD18 is involved in transendothelial migration and adherence-dependent formation of reactive oxygen species. Recently, a relationship between CD11b/CD18 expression, as an indication of neutrophil activation, and the development of ARDS has been suggested. The potential for monoclonal antibodies to adhesion proteins to reduce vascular and tissue damage has been studied in a large number of experimental models. Protective effects with anti-CD18 antibodies have been observed in a wide variety of inflammatory, immune, and ischemia-reperfusion injuries. Blockage of CD18, however, would affect all leukocytes, as would antibodies to CD11a/CD18. Targeting CD11b/CD18 would affect cells of the myeloid lineage only, which could prove to be beneficial. Anti-CD11b treatment has been used effectively to reduce tissue injury initiated by ischemia-reperfusion, complement activation, and endotoxemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Wortel
C H
CH
Medical Research Department, Repligen Corporation, Cambridge, MA 02139.
Doerschuk
C M
CM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology*; D018845:CD11 Antigens; D018821:CD18 Antigens; D002465:Cell Movement; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation; D016023:Integrins / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000209:etiology / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D016023:Integrins; D016028:Receptors, Leukocyte-Adhesion