Induction of mast cell interactions with blood vessel wall components by direct contact with intact T cells or T cell membranes in vitro
Induction of mast cell interactions with blood vessel wall components by direct contact with intact T cells or T cell membranes in vitro
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DOI：
10.1111/j.1365-2222.2004.02093.x
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发表时间：
2004-11-01
影响因子：
6.1
通讯作者：
Hershkoviz, R
中科院分区：
文献类型：
--
作者：
Brill, A;Baram, D;Hershkoviz, R
背景肥大细胞对炎症部位的免疫细胞反应具有深刻的多效性作用，在炎症部位，肥大细胞很可能不仅受到细胞外基质（ECM）和炎症介质的影响，而且还受到活化T淋巴细胞邻近的影响。我们最近报道了活化的T细胞诱导肥大细胞脱粒并释放TNF-α，并且该活化途径由淋巴细胞功能相关抗原-1（LFA-1）/细胞间粘附分子-1（ICAM-1）介导目的通过检测肥大细胞与内皮细胞的粘附，确定两种细胞类型之间的这种接触如何调节炎症环境中肥大细胞的行为。方法将人肥大细胞（HMC-1）与静息或活化的T细胞共培养，检测HMC-1与内皮细胞及ECM配体、基质衍生因子-1 α（stromal derived factor-1 alpha，SDF-1 α）的粘附性（SDF-1 α）诱导的迁移和蛋白质印迹。但不与静息T细胞一起导致肥大细胞以非常晚的抗原-4-和LFA-1-依赖性方式粘附于血管细胞粘附分子-1和ICAM-1的显著刺激。此外，活化的T细胞或T细胞膜促进HMC-1与纤维连接蛋白（FN）和层粘连蛋白的粘附。这种作用伴随着细胞外调节激酶和p38的磷酸化，但不是c-Jun N-末端激酶。重要的是，肥大细胞的粘附特性完全依赖于两种细胞类型之间的直接接触，因为无论是从活化的T细胞的上清液，也不分离的两个细胞群体与多孔膜影响肥大细胞粘附到FN。此外，当肥大细胞与来自活化T细胞的纯化膜孵育时，获得了类似的结果。这些结果表明，除了刺激肥大细胞脱粒，活化的T淋巴细胞的肥大细胞的接近可以介导的粘附肥大细胞前体的内皮配体和ECM。活化的T细胞也刺激SDF-1 α诱导的肥大细胞migration.Conclusion这两种类型的免疫细胞之间的共生关系可能有助于指导肥大细胞的特定部位的炎症，他们的效应功能是必需的。
Background Mast cells exert profound pleiotropic effects on immune cell reactions at inflammatory sites, where they are most likely influenced not only by the extracellular matrix (ECM) and inflammatory mediators but also by the proximity of activated T lymphocytes. We recently reported that activated T cells induce mast cell degranulation with the release of TNF-alpha, and that this activation pathway is mediated by lymphocyte function-associated antigen-1 (LFA-1)/intercellular adhesion molecule-1 (ICAM-1) binding.Objective To determine how this contact between the two cell types can modulate mast cell behaviour in an inflammatory milieu by examining the adhesion of mast cells to endothelial cells and ECM ligands in an integrin-dependent manner.Methods Human mast cells (HMC-1) were co-cultured with resting or activated T cells followed by testing their adhesion to endothelial cell and ECM ligands, stromal derived factor-1alpha (SDF-1alpha)-induced migration, and western blotting.Results Co-culturing HMC-1 with activated, but not with resting T cells resulted in marked stimulation of mast cell adhesion to vascular cell adhesion molecule-1 and ICAM-1 in a very late antigen-4- and LFA-1-dependent fashion. In addition, activated T cells or T cell membranes promoted HMC-1 adhesion to fibronectin (FN) and laminin. This effect was accompanied by the phosphorylation of extracellular regulated kinase and p38, but not of c-Jun N-terminal kinase. Importantly, the adhesive property of mast cells depended exclusively on the direct contact between the two cell types, since neither supernatants from activated T cells nor separation of the two cell populations with a porous membrane affected mast cell adhesion to FN. Furthermore, similar results were obtained when mast cells were incubated with purified membranes from activated T cells. These results suggest that, in addition to stimulating mast cell degranulation, the proximity of activated T lymphocytes to mast cells can mediate the adhesion of mast cell precursors to the endothelial ligands and ECM. Activated T cells also stimulated SDF-1alpha-induced mast cell migration.Conclusion This symbiotic relationship between the two types of immune cells may serve to direct mast cells to specific sites of inflammation where their effector functions are required.