Mechanism of pathogenesis of chronic inflamation

白细胞介素5(IL-5)通过与IS受体(IL-5R)相互作用而诱导嗜酸性粒细胞增殖和分化，该受体由两条不同的多肽链组成，即α和β(β)。本研究利用IL-5转基因(IL-5-TG)小鼠和IL-5Rα缺陷(IL-5Rα)小鼠，研究IL-5在嗜酸性粒细胞介导的炎症反应中的作用。[结果]1.卵清蛋白致敏的IL-5-TG小鼠在吸入卵清蛋白后24小时对乙酰胆碱表现出更明显的气道高反应性。MPT59刺激结核分枝杆菌致敏的淋巴结细胞，以I-A^b限制性的方式诱导增殖反应、IL-2和IFN-γ的产生，以及Vbeta11^+CD4^+T细胞和抗原提呈细胞的表达。用抗hIL-5R单抗进行免疫沉淀分析表明，hIL-5与hIL-5Rα结合后，BC与hIL-5Rα一起募集，但在没有IL-5.4的情况下，各亚基独立存在。对IL-5R小鼠的分析表明，IL-5在体内B-1细胞的发育和嗜酸性粒细胞的生成中起着必不可少的作用，而IL-5诱导的嗜酸性粒细胞是杀灭小鼠颅内蠕虫的有效效应细胞。

Interleukin-5 (IL-5) induces proliferation and differentiation of eosinophils by interacting with is receptor (IL-5R) which consists of two distinct polypeptide chains, alpha and beta (betac). In this project, IL-5 transgenic (IL-5-Tg) mice and IL-5R alpha deficient (IL-5Ralpha^<-/->) mice were employed to study the relative role of IL-5 in eosinophil-mediated inflamation. We also investigated the IL-5-mediated signals in human cells.[Results]1. IL-5-Tg mice actively sensitized with ovalbumin displayd more profound airway hyperreactivity in response to acetylcholine 24h after inhalation challenge with ovalbumin.2. Stimulation of M.tuberculosis-primed lymph node cells with MPT59 induced proliferative response, production of IL-2 and IFNgamma, and the epression of Vbeta11^+CD4^+T cells in conjunction with antigen-presenting cells in an I-A^b-restricted manner.3. Immunoprecipitation analysis using anti-hIL-5R mAb demonstrated that binding of hIL-5 to hIL-5Ralpha induced the recruitment of bc to hIL-5Ralpha together with hIL-5, although each subunit existed independently in the absence of IL-5.4. Analysis of IL-5Ralpha^<-/-> mice revealed that IL-5 playd an obligatory role in development of B-1 cells and eosinophilopoiesis in vivo, and IL-5-induced eosinophils served as potent effector cells in killing of intracranial worms in mice.