Stem cell factor induces mast cell adhesion to fibronectin.
Stem cell factor induces mast cell adhesion to fibronectin.
复制标题
干细胞因子诱导肥大细胞粘附到纤连蛋白。
作者：
Jarosław Dastych;D. Metcalfe
干细胞因子（SCF）或c-kit配体是由基质细胞产生的生长因子细胞因子，已知其影响肥大细胞增殖和分化。我们推测SCF也可能影响肥大细胞与结缔组织基质的粘附。为了验证这一假设，我们刺激MCP 5/L肥大细胞或小鼠骨髓来源的培养肥大细胞（BMCMC）与SCF或PMA，并观察粘附到纤连蛋白（FN）。正如预期，80 - 90%的PMA活化的MCP 5/L细胞或BMCMC粘附于FN。此外，SCF以剂量-反应方式促进MCP 5/L细胞或BMCMC与FN的粘附，当SCF浓度为10 ng/ml时，50%至60%的BMCMC与FN粘附。在SCF浓度低至200 pg/ml时观察到BMCMC粘附。SCF刺激的BMCMC与FN的粘附不需要IL-3，但依赖于用于涂覆测定表面的FN的浓度。在SCF存在下的肥大细胞粘附似乎通过整合素受体发生，因为粘附是钙依赖性的，并且可以被含有RGD（Ang，Gly，Asp）的肽阻断。SCF没有直接介导的粘附通过与c-kit的相互作用，作为FN包被的表面暴露于SCF开始之前的粘附试验没有促进粘附在可溶性SCF的情况下。相反，SCF似乎通过与c-kit相互作用激活肥大细胞来刺激与FN的粘附。因此，SCF抗体阻断粘附，大鼠和小鼠SCF刺激BMCMC粘附FN，但人SCF，不结合鼠c-kit，不刺激粘附。染料木黄酮，抑制酪氨酸激酶活性，部分抑制SCF诱导的粘附。因此，SCF刺激肥大细胞粘附，并且因为SCF在组织中正常产生，所以它可能是在生理条件下负责肥大细胞粘附到结缔组织基质的主要因素。
Stem cell factor (SCF) or c-kit ligand is a growth factor cytokine produced by stromal cells that is known to influence mast cell proliferation and differentiation. We hypothesized that SCF may also influence the adhesion of mast cells to connective tissue matrix. To examine this hypothesis, we stimulated MCP5/L mast cells or murine bone marrow-derived cultured mast cells (BMCMC) with either SCF or PMA and observed adhesion to fibronectin (FN). As expected, 80 to 90% of PMA-activated MCP5/L cells or BMCMC adhered to FN. In addition, SCF promoted MCP5/L cell or BMCMC adhesion to FN in a dose-response fashion with 50 to 60% of BMCMC adhering to FN at a concentration 10 ng/ml of SCF. BMCMC adhesion was observed with as little as 200 pg/ml of SCF. Adhesion of SCF stimulated BMCMC to FN did not require IL-3, but was dependent on the concentration of FN used to coat the assay surface. Mast cell adhesion in the presence of SCF appeared to occur through an integrin receptor as adhesion was calcium dependent and could be blocked by an RGD (Ang, Gly, Asp)-containing peptide. SCF did not directly mediate adhesion through interaction with c-kit, as FN-coated surfaces exposed to SCF before initiation of the adhesion assay did not promote adhesion in the absence of soluble SCF. Rather, SCF appeared to stimulate adhesion to FN by activating mast cells through its interaction with c-kit. Thus, antibody to SCF blocked adhesion, and rat and murine SCF stimulated BMCMC adhesion to FN, but human SCF, which does not bind to murine c-kit, did not stimulate adhesion. Genistein, which inhibits tyrosine kinase activity, partially inhibited SCF-induced adhesion. SCF thus stimulates mast cell adhesion and, because SCF is produced normally in tissues, it may be a major factor responsible for the adhesion of mast cells to connective tissue matrix under physiologic conditions.