W‐7, a calmodulin antagonist, primes the stimulation of human neutrophil respiratory burst by formyl peptides and platelet‐activating factor

FEBS Letters

Périanin, Axel¹  Pedruzzi, Eric²  Hakim, Jacques² 

[1] Département de Pharmacologie, CNRS URA 1534 Hôpital Cochin, Paris, France;Laboratoire d' Hématologie, INSERM Unité 294, CHU Xavier Bichat, Paris, France

关键词: Neutrophil;    Respiratory burst;    Calmodulin;    W-7;    Chemoattractant;    PMN;    polymorphonuclear leukocytes;    fMLP;    Nformyl-methionyl-leucyl-phenylalanine;    Paf;    platelet-activating factor;    PMA;    phorbol myristate;    PKC;    protein kinase C;    IC50;    drug concentration that reduces control values by 50%;    W-7;    N-(6-aminohexyl)-5-chloro-1-naphtalenesulphonamide;   

DOI  :  10.1016/0014-5793(94)80487-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Low concentrations of the calmodulin antagonist W-7 (1-1μM) enhanced the respiratory burst (RB) of human polymorphonuclear leukocytes (PMN) stimulated by N-formyl-methionyl-leucyl-phenylalanine, whereas high drug concentrations (above 20 μM) depressed it. The maximal increase obtained with 5–10μM 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 μM). 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 1C₅₀ of approximately 20 and 8 μM, respectively. These data show the enhancing effect of W-7 on chemoattractant-mediated RB and suggest that RB priming may involve calmodulindependent regulation of chemoattractant-mediated early signalling events.

【 授权许可】

Unknown