Effects of cyclosporin A and FK-506 on stem cell factor-induced histamine secretion and growth of human mast cells

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:98

Article

Sperr, WR ; Agis, H ; Czerwenka, K ; Virgolini, I ; Bankl, HC ; Muller, MR ; Zsebo, K ; Lechner, K ; Valent, P

关键词: mast cells;    histamine;    c-kit;    stem cell factor;    IgE;    tryptase;   

DOI  :  10.1016/S0091-6749(96)70163-X

来源: Elsevier

【 摘 要 】

Stem cell factor (SCF) is a key regulator of human mast cells (MCs) and a potential mediator of allergy. In this study the effects of cyclosporin A (CSA) and FK-506, two potent immunosuppressive drugs, on SCF-dependent histamine release and growth of human MCs were analyzed. Preincubation of tissue MCs with CSA (3 mu g/ml) resulted in inhibition of histamine release provoked by either recombinant human (rh) SCF (70.3% +/- 20.6% inhibition, p<0.001) or anti-IgE (76.7%+/-21.9%, p<0.001) or by rhSCF+ anti-IgE (77.4%+/-13.9%, p<0.001). Almost the same inhibition was produced by FK-506 (rhSCF: 82.0%+/-18.9% inhibition, p<0.001; anti-IgE: 71.5%+/-16.7%, p<0.001; rhSCF+ anti-IgE: 70.0%+/-7.3%, p<0.001). The effects of CSA and FK-506 on SCF-dependent release of histamine were dose-dependent (IC50: CSA, 1 to 10 ng/ml; FK-506, 0.3 to 3 ng/ml. IC50 values about three to 10 times higher were found for MCs preincubated with rhSCF before anti-IgE activation, compared with anti-IgE or SCF alone. SCF-dependent differentiation of human MCs was analyzed in a long-term suspension culture system (n=6). Unexpectedly, CSA and FK-506 were unable to suppress, but even enhanced SCF-dependent growth of MCs and formation of MC tryptase in long-term culture. Together, CSA and FK-506 inhibit SCF-dependent release of histamine from human MCs and even augment SCF-dependent growth of human MCs in long-term culture.

【 授权许可】

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