INHIBITION OF FIBRIN DEPOSITION ON THE SUBENDOTHELIUM BY A MONOCLONAL-ANTIBODY TO POLYMORPHONUCLEAR LEUKOCYTE INTEGRIN CD11B - STUDIES IN AFLOW SYSTEM

Background and Objective. The development of prothrombotic and procoag ulant states may be regulated by direct platelet-leukocyte contact med iated by membrane receptors. We have investigated the role of CD11b in tegrin in polymerphonuclear leukocytes (PMN) on fibrin formation and p latelet reactivity with vascular subendothelium. Methods. Studies were carried out following a well-established perfusion model, employing e ither citrated blood, where fibrin formation is blocked, or blood anti coagulated with low molecular weight heparin, which allows thrombin an d fibrin formation. Isolated PMN or platelets were treated with specif ic monoclonal antibodies to CD11b or to CD62P, respectively, and incor porated in reconstituted blood. Results. Treatment of PMN with anti-CD 11b significantly decreased the percentage of surface covered with a t hick layer (>5 mu m) 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 n umber of adherent leukocytes (7.9+/-1.2 mu m vs 10.6+/-1.4 mu m in con trol, p<0.05; and 87+/-8 PMN/mm(2) vs 186+/-25 PMN/mm(2) 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 obs erved in the heparinized samples. Treatment of platelets with anti-CD6 2P did not significantly modify any of the parameters studied. Interpr etation and Conclusions. Our results indicate that PMN have a role in promoting fibrin deposition under flow conditions, through the partici pation of CD11b integrin. Under our experimental conditions, this effe ct does not seem to be influenced by CD62P expressed on activated plat elets. (C) 1997, Ferrata Storti Foundation.