ARACHIDONIC-ACID METABOLISM AND THE ADHESION OF HUMAN POLYMORPHONUCLEAR LEUKOCYTES TO CULTURED VASCULAR ENDOTHELIAL-CELLS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 62  (4) , 889-895
Abstract
Polymorphonuclear leukocytes (PMN) adhere to the vascular endothelial lining in vivo and to the surfaces of cultured endothelial cells in vitro, but the mechanisms of these cellular interactions remain unclear. Arachidonic acid metabolites, both cyclooxygenase- and lipoxygenase-derived, were shown to influence PMN locomotion, secretion and adhesion to artifical surfaces. To determine whether such mediators also are involved in regulating PMN-endothelial cell interactions, the effects of prostacyclin and various inhibitors of arachidonic acid metabolism on the adherence of radiolabeled PMN to cultured bovine aortic endothelial cells were examined. Confluent endothelial monolayers were incubated with washed suspensions of radiolabeled human PMN (which contained < 1% platelet contamination) at 37.degree. C for 30 min, then subjected to a standardized wash procedure and the number of adherent leukocytes determined radiometrically. Under basal conditions, i.e., in the absence of exogenous activating stimuli, 4163 .+-. 545 PMN adhered per mm of endothelial suface (mean .+-. SEM [standard error of the mean], n = 12). This basal adhesion (which corresponds to .apprx. 4.5 leukocytes per endothelial cell) was unaffected when the leukocytes and endothelial monolayers were pretreated with cyclooxygenase inhibitors (100 .mu.M aspirin or 1-5 .mu.M indomethacin) or PGI2 [prostaglandin I2] (10-9-106 M). Thus, basal PMN-endothelial adhesion in this in vitro model system does not appear to be dependent on endogenous cyclooxygenase derivatives of arachidonate or to be sensitive to inhibition by exogenous prostacyclin. Leukocyte adhesion was significantly reduced by pretreatment with 5,8,11,14- or 4,7,10,13-eicosatetraynoic acid, 0.5-5 mM sodium salicylate or 10-1000 .mu.M indomethacin, antiinflammatory agents that can interfere with the metabolism of arachidonic acid via non-cyclooxygenase-dependent mechanisms. These observations may be relevant to the interactions of circulating PMN with vascular endothelium under both physiologic and pathophysiologic conditions in vivo.