Study on mutual offects of eosinophils and fibroblasts in the pathogenesis of brochial asthma

虽然嗜酸性粒细胞（Eos）和成纤维细胞（Fb）在哮喘患者的支气管粘膜下非常接近，并且被认为在支气管哮喘的发病机制中起重要作用，但Eos和Fb之间的相互作用尚未完全阐明。1997年，我们检测了在人肺Fb存在下培养的人Eos细胞中嗜酸性阳离子蛋白（ECP）的释放。将健康供体的Eos在加或不加C5a的情况下，在加或不加某些细胞因子的人胎儿肺Fb存在下培养16小时，用RIA法测定上清液中的ECP。仅当Eos和Fb分别被C5a和TNF激活时，ECP释放增强，而Eos或Fb均被激活时，ECP释放无显著增强。当白细胞介素β刺激Fb时，Ca激活的Eos的ECP释放也增强。在共培养的Eos和Fb中，刺激对ECP释放的增强被抗GM-CSF单克隆抗体部分抑制，并伴有Eos对Fb的粘附增强。抗icam -1单抗、抗cd18单抗和抗cd29单抗显著抑制ECP增强和Eos对Fb的粘附增强。1998年，我们研究了Eos对Fb中SCF产量的影响。结果如下：当Fb被几种细胞因子的IL-4激活时，Fb的SCF生成增强。当在培养系统中加入活化的Eos和IL-4时，Fb的SCF产量进一步增强。综上所述，Fb可能影响Eos脱粒，而Eos可能影响Fb SCF的产生。提示两种细胞的相互作用可能导致哮喘的加重和慢性。

Although eosinophils (Eos) and fibroblasts (Fb) are closely approximated in the bronchial submucosae of asthmatics, and are believed to play important roles in the pathogenesis of bronchial asthma, the interaction between Eos and Fb has not been thoroughly elucidated. 1n1997, we examined eosinophil cationic protein (ECP) release from human Eos cultured in the presence of human lung Fb. Eos from healthy donors were cultured with or without C5a for 16 h in the presence of human fetal lung Fb which had previously been incubated with or without some cytokines far 4 h. ECP in supernatants was measured by RIA The results were as follows. ECP release was potentiated only when both Eos and Fb were activated by C5a and TNF, respectively, while it was not significantly potentiated when either Eos or Fb were activated. ECP release from Eos activated by Ca was also potentiated when Fb were stimulated by IL-lbeta. The enhancement of ECP release in cocultured Eos and Fb with stimulation was partly inhibited by monoclonal antibodies against GM-CSF and was accompanied by the enhancement of adhesion of Eos to Fb. Anti-ICAM-1 mAb, anti-CDl8 mAb and anti-CD29 mAb significantly inhibited ECP enhancement and the enhancement of adhesion of Eos to Fb.In 1998, we examined the effect of Eos on SCF production from Fb. The results were as follows. SCF production from Fb was potentiated when Fb were activated by IL-4 of several cytokines. SCF production from Fb were further potentiated when activated Eos were added to culture system, in addition to IL-4. In summary, Fb may influence Eos degranulation, while Eos may have effects on Fb SCF production. It is suggested that the mutual effects of both cells may lead to the exacerbation and chronicity of asthma.