W-7, A CALMODULIN ANTAGONIST, PRIMES THE STIMULATION OF HUMAN NEUTROPHIL RESPIRATORY BURST BY FORMYL PEPTIDES AND PLATELET-ACTIVATING-FACTOR

Low concentrations of the calmodulin antagonist W-7 (1-10 mu M) enhanced the respiratory burst (RB) of human polymorphonuclear leukocytes (PMN) stimulated by N-formyl-methionyl-leucyl-phenylalanine, whereas high drug concentrations (above 20 mu M) depressed it. The maximal increase obtained with 5-10 mu M W-7 affected both initial rate (50%) and total superoxide anion production (150%). W-7 also primed both parameters of the RB mediated by platelet-activating factor, although higher drug concentrations were required (15-50 mu M). By contrast, W-7 depressed the RB induced by the calcium ionophore A23187 and by a protein kinase C activator, phorbol myristate acetate, with an IC50 of approximately 20 and 8 mu M, respectively. These data show the enhancing effect of W-7 on chemoattractant-mediated RB and suggest that RB priming may involve calmodulin-dependent regulation of chemoattractant-mediated early signalling events.