FK506 suppresses neutrophil chemoattractant production by peripheral blood mononuclear cells

被引:32
作者
Sasakawa, Y [1 ]
Sakuma, S [1 ]
Higashi, Y [1 ]
Sasakawa, T [1 ]
Amaya, T [1 ]
Goto, T [1 ]
机构
[1] Fujisawa Pharmaceut Co Ltd, Med Biol Res Labs, Yodogawa Ku, Osaka 5328514, Japan
关键词
FK506 (Tacrolimus); neutrophil chemotaxis; interleukin-8; mononuclear cell peripheral blood;
D O I
10.1016/S0014-2999(00)00592-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
To understand the mechanism of action of FK506 (Tacrolimus) on neutrophil chemotaxis, we examined its effect on human neutrophil chemotaxis and neutrophil chemoattractant production by peripheral blood mononuclear cells. FK506 and cyclosporin A had no direct suppressive effect on neutrophil chemotaxis induced by interleukin-8, leukotriene B-4, complement 5a (C5a), zymosan-activated serum and formyl-Met-Leu-Phe (fMLP). FK506 and cyclosporin A only slightly suppressed the chemotactic activity of platelet-activating factor (PAF). Dexamethasone did not inhibit the chemotactic activity of any chemoattractant. The supernatant of peripheral blood mononuclear cells stimulated with anti-CD3 and CD2 antibodies induced neutrophil chemotaxis. FK506 and cyclosporin A suppressed the chemotactic activity of the supernatant in parallel to the suppression of interleukin-8 production by peripheral blood mononuclear cells. Anti-interleukin-8 antibody completely suppressed the chemotactic activity of the supernatant without drugs. These studies indicate that FK506 may exert a beneficial effect on human inflammatory diseases by suppressing neutrophil chemotaxis secondary to inhibition of chemoattractant (for example, interleukin-8) production by leukocytes. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:281 / 288
页数:8
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