抽象
支气管粘膜中嗜酸性粒细胞累积和活化的机制对于哮喘发病机制至关重要。在支气管基底膜下方的专用成纤维细胞,肌成纤维细胞,近距离渗透嗜酸性粒细胞的位置可能使肌纤维细胞能够调节嗜酸性粒细胞存活和在哮喘中的功能。本研究的目的是探讨支气管肌纤维素对体外嗜酸性粒细胞存活的影响。来自人外周血的嗜酸性粒细胞暴露于来自支气管肌纤维素细胞和肌纤维细胞调节培养基的细胞培养物。评估嗜酸性粒细胞活力,并在共培养上清液中检测粒细胞/巨噬细胞菌刺激因子(GM-CSF)产生,并在肌纤维细胞中的信使核糖核酸(mRNA)中。嗜酸性粒细胞存活率显着增加,嗜酸性粒细胞凋亡被肌纤维细胞共培养抑制。来自肿瘤坏死因子-α(TNF-α)的条件培养基(TNF-α) - 刺激的肌纤维细胞也延长了嗜酸性粒细胞存活。通过GM-CSF抗体可以阻断这种效果。来自植物纤维细胞的GM-CSF mRNA和来自肌纤维细胞的分泌物在共培养物中和嗜酸性粒细胞调节培养基中增加。向共培养物中添加到TNF-α和白细胞介素-1α(IL-1α)的抗体导致嗜酸性粒细胞存活和GM-CSF水平显着降低。 Blocking of fibronectin in the co-cultures did not affect the eosinophil survival enhancing activity. Prednisolone inhibited the eosinophil survival enhancing activity of the co-cultures by suppression of GM-CSF production. Soluble eosinophil-derived cytokines are involved in the interaction of eosinophils with myofibroblasts, which results in a tumour necrosis factor-alpha/interleukin-1 alpha mediated release of granulocyte/macrophage colony-stimulating factor from myofibroblasts. Bronchial myofibroblasts can, thereby, contribute to allergic inflammation by granulocyte/macrophage colony-stimulating factor-mediated inhibition of eosinophil apoptosis.