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) enhanc ed the respiratory burst (RB) of human polymorphonuclear leukocytes (P MN) stimulated by N-formyl-methionyl-leucyl-phenylalanine, whereas hig h drug concentrations (above 20 mu M) depressed it. The maximal increa se obtained with 5-10 mu M W-7 affected both initial rate (50%) and to tal superoxide anion production (150%). W-7 also primed both parameter s of the RB mediated by platelet-activating factor, although higher dr ug concentrations were required (15-50 mu M). By contrast, W-7 depress ed the RB induced by the calcium ionophore A23187 and by a protein kin ase C activator, phorbol myristate acetate, with an IC50 of approximat ely 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 ea rly signalling events.