The effects of some antirheumatic drugs on an in vitro model of human polymorphonuclear leucocyte chemokinesis

Abstract

1 A rapid, reproducible in vitro assay for studying the chemokinetic movement of human polymorphonuclear leucocytes (PMNs) is described. Two synthetic peptides, formyl methionyl-leucyl-phenylalanine (FMLP) and formyl methionyl-phenylalanine (FMP), were used as a standard chemokinesins. 2 Maximal chemokinetic movement was observed with peptide concentrations of 2.5 nM (FMLP) and 100 muM (FMP). EC50 values of 650.0 +/- 60.0 pM and 27.0 +/- 3.5 muM respectively are similar to those reported for chemotactic activity of the peptides in micropore filter assays. 3 The PMN chemokinetic response to FMLP was enhanced by histamine (100 nM) and vitamin C (2.5 muM). 4 Human serum albumin was shown to induce chemokinesis but to antagonize the response to FMLP in a dose-related fashion. Fibrinogen similarly antagonized the cell response to peptide. 5 Levamisole (250 nM to 2.5 muM) significantly potentiated the chemokinetic responses to FMLP and FMP in a dose-related manner. The chemokinetic response to FMLP was unaffected by D-penicillamine (250 muM to 10 mM) while alclofenac (500 muM to 1 mM), salicylic acid (250 muM to 10 mM) and indomethacin (100 muM to 1 mM) caused dose-related inhibition.