ARACHIDONIC-ACID RELEASE AND PLATELET-ACTIVATING-FACTOR FORMATION BY STAUROSPORINE IN HUMAN NEUTROPHILS CHALLENGED WITH N-FORMYL PEPTIDE

被引:17
|
作者
MULLER, S [1 ]
NIGAM, S [1 ]
机构
[1] FREE UNIV BERLIN, KLINIKUM STEGLITZ, DEPT GYNECOL, W-1000 BERLIN 45, GERMANY
关键词
NEUTROPHILS; ARACHIDONIC ACID; PAF (PLATELET-ACTIVATING FACTOR; PAF-ACETHER); STAUROSPORINE; PHOSPHOLIPASE-A2;
D O I
10.1016/0014-2999(92)90176-5
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Staurosporine, a putative protein kinase C (PKC) inhibitor, increased the release of [C-14]arachidonic acid dose dependently between 100 nM and 1000 nM in human neutrophils challenged with 100 nM N-formyl-methionine-leucine-phenylalanine (FMLP). Staurosporine also increased the formation of leukotriene B4 (LTB4) and platelet-activating factor (PAF) in a dose-dependent manner. In addition, exogenously added lyso-PAF further augmented [H-3]PAF formation in staurosporine-pretreated human neutrophils stimulated by FMLP, thus suggesting an activation of acetyl-CoA: lyso-PAF acetyltransferase by staurosporine. The potentiation of [C-14]arachidonic acid release and [H-3]PAF formation by staurosporine was further enhanced in the presence of 100 nM phorbol 12-myristate 13-acetate (PMA), which pinpoints a mechanism other than the modulation of PKC in this process, inasmuch as staurosporine antagonizes PMA-induced O2- production and [H-3]PAF formation. Additional studies with other putative PKC inhibitors also revealed the potentiating effects of 1-(5-isoquinolinsulfonyl)-2-methylpiperazine (H-7, 20-mu-M) and sphingosine (2.5-mu-M) on FMLP-induced [C-14]arachidonic acid release and [H-3]PAF formation. We therefore conjecture that staurosporine-sensitive protein kinases including PKC are not involved in the activation of phospholipase A2 and acetyl-CoA: lyso-PAF acetyltransferase.
引用
收藏
页码:251 / 258
页数:8
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