Sperr W R, Czerwenka K, Mundigler G, Müller M R, Semper H, Klappacher G, Glogar H D, Lechner K, Valent P
Department of Internal Medicine I, University of Vienna, Austria.
Int Arch Allergy Immunol. 1993;102(2):170-5. doi: 10.1159/000236568.
Recent data suggest that stem cell factor (SCF or c-kit ligand, KL) is a major regulator of human mast cells (MCs). In the present study, MCs derived from the lung (n = 8), uterus (n = 14) and heart (n = 4) were analyzed for expression of c-kit receptor and for responses to recombinant SCF. MCs of all organs tested were recognized by mAbs to c-kit (YB5.B8, SR-1) as assessed by combined toluidine blue/immunofluorescence staining. Activation by rhSCF (10 ng/ml, 60 min) resulted in histamine release from lung MCs (SCF 12.8 +/- 2.7% histamine release; control 2.8 +/- 0.8%, p < 0.01), uterus MCs (SCF 16.8 +/- 5.8%; control 5.2 +/- 2.5%, p < 0.01) and heart MCs (SCF 18.4 +/- 2.6%; control 1.7 +/- 0.23%, p < 0.01). Short-term pre-incubation with rhSCF (15 min) did not result in histamine secretion (p > 0.05), but in an increase (lung 2.4 +/- 1.0 fold; uterus 2.1 +/- 1.1 fold, and heart 2.0 +/- 0.4 fold) of alpha IgE-induced mediator release (p < 0.05). The effects of SCF were dose-dependent (maximum responses at 10-100 ng/ml) and dependent on extracellular calcium. A monoclonal antibody to SCF was found to inhibit the effects of SCF on MCs. Furthermore, MCs could be desensitized specifically by pre-incubation of MCs with rhSCF in Ca-free medium. Together, these data suggest that SCF triggers mediator secretion from MCs in various organs via binding to the c-kit receptor.
近期数据表明，干细胞因子（SCF或c-kit配体，KL）是人类肥大细胞（MCs）的主要调节因子。在本研究中，对来自肺（n = 8）、子宫（n = 14）和心脏（n = 4）的MCs进行了c-kit受体表达及对重组SCF反应的分析。通过甲苯胺蓝/免疫荧光联合染色评估，所有测试器官的MCs均被抗c-kit单克隆抗体（YB5.B8、SR-1）识别。重组人干细胞因子（rhSCF，10 ng/ml，60分钟）激活后，导致肺MCs组胺释放（SCF组组胺释放率为12.8±2.7%；对照组为2.8±0.8%，p<0.01）、子宫MCs组胺释放（SCF组为16.8±5.8%；对照组为5.2±2.5%，p<0.01）和心脏MCs组胺释放（SCF组为18.4±2.6%；对照组为1.7±0.23%，p<0.01）。rhSCF短期预孵育（15分钟）未导致组胺分泌（p>0.05），但使αIgE诱导的介质释放增加（肺为2.4±1.0倍；子宫为2.1±1.1倍，心脏为2.0±0.4倍）（p<0.05）。SCF的作用呈剂量依赖性（10 - 100 ng/ml时反应最大）且依赖细胞外钙。发现一种抗SCF单克隆抗体可抑制SCF对MCs的作用。此外，在无钙培养基中用rhSCF预孵育MCs可使其特异性脱敏。总之，这些数据表明SCF通过与c-kit受体结合触发各器官MCs的介质分泌。
