RESUMO
There is increasing interest in the role of blood polymorphonuclear leucocytes (PMNs) in the pathogenesis of sickle cell crisis. We studied the adherence of PMNs from 18 sickle cell patients in crisis, 25 out of crisis and 43 healthy subjects (controls) to monolayers of human umbilical cord endothelium which were either untreated or pretreated with the inflammatory cytokine, tumour necrosis factor (TNFO). The PMN's from patients in crisis were more adherent than control PMN's to untreated endothelial monlayers (mean 53 percent increase; p<0.001 and TNFO-treated monlayers (means 42 percent increase; p<0.002). Increased adhesiveness was not associated with an abnormal expression of the adhesion molecules CD11a, CD11b, CD11c, CD18, CD62L or CD15. There was an increase in the number of PNM's expressing CD64 in patients in crisis (median value, 44 percent) compared with patients out of crisis (median 21 percent; P=0.025) and controls (median 6.5 percent; P<0.001). Sera from patients in crisis had normal levels of G-CSF, GM-CSF, IFNç, TNFOIl-1, IL-6 or IL-8 and did not modify the adherence of PMN's or their expression of CD64. Only IFNç induced CD64 expression on PMN's but this effect was not associated with enhanced binding to endothelium. Most PMN's bound to endothelial monolayers were CD64-positive and CD64-enriched PMN's were 7 times more adherent to endothelial monlayers than CD64-depleted PMNs. Two of the three anti-Cd64 antibodies used in our antibody blocking studies (clones 32.2 and 197) partially inhibited the biding of sickle cell PMNs to untreated endothelium (mean 33 percent; p=0.01 and 21 percent; p=0.03 inhibition respectively), whereas only one (clone 197) inhibited binding to TNFO-treated endothelium(mean 29 percent inhibition; p=0.004). An enhanced PMN adhesion to vascular endothelium could contribute to the vascular occlusion that characterises the acute crisis of sickle cell disease. (AU)
