ACECLOFENAC, A NEW NONSTEROIDAL ANTIINFLAMMATORY DRUG, DECREASES THE EXPRESSION AND FUNCTION OF SOME ADHESION MOLECULES ON HUMAN NEUTROPHILS

Objective. To study the effect of aceclofenac, a new nonsteroidal anti inflammatory drug (NSAID), on the expression and function of adhesion molecules in human neutrophils. Methods, We used flow cytometry analys is to determine peripheral blood neutrophil expression of L-selectin, CD11a, CD11b, CD31, CD43, CD44, and intercellular adhesion molecule 3 (ICAM-3) surface adhesion molecules after treatment with aceclofenac, diclofenac, or dexamethasone. Granular enzyme activity was quantitated in extracellular medium of neutrophils treated with different NSAID. In vitro adhesion assays were developed to examine the effects of acec lofenac on both neutrophil adhesion to tumor necrosis factor alpha sti mulated human umbilical vein endothelial cells under nonstatic conditi ons, and homotypic neutrophil aggregation induced by anti-ICAM-3 and a nti-CD18 monoclonal antibodies (Mab). Results, Aceclofenac induced a d ramatic decrease of L-selectin expression, whereas a moderate and slig ht decrement of CD43 and ICAM-3 expression was also observed. In contr ast, the expression of other adhesion molecules by neutrophils was una ffected (CD11a, CD31, CD44) or slightly increased (CD11b). Cell adhesi on assays, performed under nonstatic conditions, revealed that aceclof enac significantly diminished the L-selectin dependent neutrophil adhe sion to endothelial cells. Neutrophil aggregation induced with anti-CD 43 Mab was also significantly inhibited by aceclofenac. Conclusion. Ac eclofenac had a faster and more potent effect than the other NSAID stu died, mainly on the expression of cell adhesion molecules. This new NS AID efficiently interferes with neutrophil adhesion to endothelium and this effect may represent an additional relevant mechanism in its ant iinflammatory activity.