Effects of benoxaprofen on the binding to and inactivation of leucoattractants by human polymorphonuclear leucocytesin vitro

Abstract

Benoxaprofen was previously found to inhibit the random and leucoattractant-induced migration of human polymorphonuclear leucocytes in vitro by a pro-oxidative mechanism [1]. In this study the effects of benoxaprofen on the binding to PMNL of the synthetic chemotactic tripeptide FMLP, on the oxidative inactivation of this leucoattractant by PMNL and on PMNL chemotaxis, chemokinesis and orientation in an FMLP gradient have been investigated. At concentrations of 10(-5) M (3 micrograms/ml) benoxaprofen inhibited PMNL random and leucoattractant-induced migration and increased PMNL membrane-associated oxidative metabolism and cellular auto-oxidation. These effects of benoxaprofen on PMNL migration and auto-oxidation were prevented by the anti-oxidant cysteine (10(-3) M). Benoxaprofen inhibited both FMLP-induced chemotaxis and chemokinesis but did not affect the binding of radiolabelled FMLP to PMNL or orientation of the cells in a positive gradient of the leucoattractant. Benoxaprofen at concentrations of 5 X 10(-5) M significantly increased the oxidative inactivation of FMLP by PMNL. Inhibition of PMNL migration by benoxaprofen is mediated by the two different pro-oxidative mechanisms, viz. a cell-directed auto-oxidative mechanism and potentiation of the oxidative inactivation of leucoattractants by PMNL.