Basal PMN-endothelial adhesion was unaffected by cyclooxygenase inhibitors or prostacyclin, but was significantly reduced by inhibitors of non-cyclooxygenase-dependent arachidonic acid metabolism.
Basal PMN-endothelial adhesion in vitro is not dependent on endogenous cyclooxygenase derivatives but is reduced by inhibitors of non-cyclooxygenase-dependent arachidonic acid metabolism.
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, have been shown to influence PMN locomotion, secretion, and adhesion to artificial surfaces. To determine whether such mediators also are involved in regulating PMN-endothelial cell interactions, we have examined the effects of prostacyclin and various inhibitors of arachidonic acid metabolism on the adherence of radiolabeled PMN to cultured bovine aortic endothelial cells. Confluent endothelial monolayers were incubated with washed suspensions of radiolabeled human PMN (which contained less than 1% platelet contamination) at 37 degrees 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, 4,163 +/- 545 PMN adhered per square millimeter of endothelial surface (mean +/- SEM, n = 12). This basal adhesion (which corresponds to approximately 4–5 leukocytes per endothelial cell) was unaffected when the leukocytes and endothelial monolayers were pretreated with cyclooxygenase inhibitors (100 microM aspirin or 1–5 microM indomethacin) or PGI2 (10(-9)-10(6) 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. In contrast, 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 10–1,000 microM 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.
Buchanan et al. (Sat,) reported a other. Arachidonic acid metabolism inhibitors and prostacyclin vs. Basal conditions (absence of exogenous activating stimuli) was evaluated on Number of adherent leukocytes per square millimeter of endothelial surface. Basal PMN-endothelial adhesion was unaffected by cyclooxygenase inhibitors or prostacyclin, but was significantly reduced by inhibitors of non-cyclooxygenase-dependent arachidonic acid metabolism.