Inhibition of fibrin deposition on the subendothelium by a monoclonal antibody to polymorphonuclear leukocyte integrin CD11b. Studies in a flow system

Abstract

BACKGROUND AND OBJECTIVE: The development of prothrombotic and procoagulant states may be regulated by direct platelet-leukocyte contact mediated by membrane receptors. We have investigated the role of CD11b integrin in polymorphonuclear leukocytes (PMN) on fibrin formation and platelet reactivity with vascular subendothelium. METHODS: Studies were carried out following a well-established perfusion model, employing either citrated blood, where fibrin formation is blocked, or blood anticoagulated with low molecular weight heparin, which allows thrombin and fibrin formation. Isolated PMN or platelets were treated with specific monoclonal antibodies to CD11b or to CD62P, respectively, and incorporated in reconstituted blood. RESULTS: Treatment of PMN with anti-CD11b significantly decreased the percentage of surface covered with a thick layer (> 5 microns) of fibrin (34.8 +/- 3.3% vs 53.3 +/- 4.9% in control, p < 0.05); it also reduced the average height of fibrin layer and the number of adherent leukocytes (7.9 +/- 1.2 microns vs 10.6 +/- 1.4 microns in control, p < 0.05; and 87 +/- 8 PMN/mm2 vs 186 +/- 25 PMN/mm2 in control, p < 0.05) respectively. Treatment of PMN with CD11b did not significantly affect the attachment of platelets onto the subendothelium when using citrated blood, though a slight decrease in platelet adhesion was observed in the heparinized samples. Treatment of platelets with anti-CD62P did not significantly modify any of the parameters studied. INTERPRETATION AND CONCLUSIONS: Our results indicate that PMN have a role in promoting fibrin deposition under flow conditions, through the participation of CD11b integrin. Under our experimental conditions, this effect does not seem to be influenced by CD62P expressed on activated platelets.