Sperr W R, Agis H, Czerwenka K, Virgolini I, Bankl H C, Müller M R, Zsebo K, Lechner K, Valent P
Department of Internal Medicine I, University of Vienna, Austria.
J Allergy Clin Immunol. 1996 Aug;98(2):389-99. doi: 10.1016/s0091-6749(96)70163-x.
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 micrograms/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.
干细胞因子（SCF）是人类肥大细胞（MCs）的关键调节因子，也是过敏反应的潜在介质。在本研究中，分析了两种强效免疫抑制药物环孢素A（CSA）和FK - 506对SCF依赖性组胺释放及人类MCs生长的影响。用CSA（3微克/毫升）对组织MCs进行预孵育，可抑制重组人（rh）SCF（抑制率70.3%±20.6%，p<0.001）、抗IgE（抑制率76.7%±21.9%，p<0.001）或rhSCF +抗IgE（抑制率77.4%±13.9%，p<0.001）所引发的组胺释放。FK - 506产生了几乎相同的抑制效果（rhSCF：抑制率82.0%±18.9%，p<0.001；抗IgE：抑制率71.5%±16.7%，p<0.001；rhSCF +抗IgE：抑制率70.0%±7.3%，p<0.001）。CSA和FK - 506对SCF依赖性组胺释放的影响呈剂量依赖性（半数抑制浓度：CSA为1至10纳克/毫升；FK - 506为0.3至3纳克/毫升）。与单独使用抗IgE或SCF相比，在抗IgE激活前用rhSCF预孵育的MCs的半数抑制浓度值高出约三至十倍。在长期悬浮培养系统（n = 6）中分析了人类MCs的SCF依赖性分化。出乎意料的是，在长期培养中，CSA和FK - 506无法抑制，反而增强了MCs的SCF依赖性生长以及MC类胰蛋白酶的形成。总之，CSA和FK - 506抑制人类MCs中SCF依赖性组胺释放，甚至在长期培养中增强人类MCs的SCF依赖性生长。
