INFLUENCE OF ANTIINFLAMMATORY DRUGS ON ADHESION OF NEUTROPHILS TO ENDOTHELIAL-CELLS CULTURED ON MICROCARRIERS - A NOVEL IN-VITRO SYSTEM AS AN ALTERNATIVE TO ANIMAL EXPERIMENTATION

Pharmacological control of inflammation by steroidal (SAIDs) and nonst eoidal (NSAIDs) antiinflammatory drugs is of substantial clinical impo rtance. To reduce the number of animals used in pharmacological and to xicological evaluation of these drugs we developed a novel assay to de termine adhesion of bovine neutrophils (PMN) to bovine aortic endothel ial cells (BAEC) cultured on microcarriers in a flow-through system. P retreatment of BAEC with thrombin (10(-7)-10(-4) M) led to a dose-depe ndent increase of PMN-adhesion (10(-6)-10(-4) M:P < 0.05); platelet-ac tivating factor (10(-9) M) and 1:200 diluted zymosan-activated serum ( ZAS) had similar effects (P < 0.001). Pretreatment of PMN with SAIDs ( 50.9 and 509 muM dexamethasone, 12.2 and 24.4 muM flumethasone) did in hibit adhesion to ZAS-treated BAEC dose-dependently. Pretreatment of P MN with NSAIDs had a less consistent influence on adhesion to ZAS-stim ulated BAEC. While phenylbutazone (0.33 and 3.3 mM), diclofenac (0.392 and 0.574 mM), indomethacine (0.436 and 0.872 mM), and acetylsalicyli c acid (3.47 and 16.94 mM) induced dose-dependent inhibition of PMN-ad hesion to ZAS-treated BAEC, piroxicam (0.377 and 0754 mM) inhibited PM N-adhesion strongly (P < 0.001) but not dose-dependently, and ketoprof ene (0.614 and 1.228 mM) had no effect on PMN-adhesion. The method pre sented here is efficient for evaluating the pharmacological modulation of PMN interaction with endothelial cells, and useful for studying fu rther aspects of endothelial cell biology.