Chensue S W, Bienkowski M, Eessalu T E, Warmington K S, Hershey S D, Lukacs N W, Kunkel S L
Department of Pathology, Veterans Affairs Medical Center, Ann Arbor, MI.
J Immunol. 1993 Oct 1;151(7):3654-62.
This study examined the role of IL-1 receptor antagonist protein (IRAP) in the regulation of the immune/inflammatory response to schistosome eggs. Initial screening for IRAP-specific mRNA transcripts by reverse transcriptase and primer-directed polymerase chain reactions suggested significant endogenous IRAP synthesis in lungs with Schistosoma mansoni egg-induced hypersensitivity granulomas but not in normal lungs or lungs with non-immune bead granulomas. Direct detection using mIRAP-specific antibodies corroborated the RNA studies. Both ELISA and immunohistochemical studies revealed significant spontaneous IRAP production in cultures of isolated egg granulomas and regional reactive lymphoid tissue that could be localized largely but not exclusively to macrophages. Synchronously developing secondary schistosome egg granulomas showed accelerated and augmented IRAP production compared with primary lesions, paralleling granuloma cellularity and growth kinetics. Nonimmune T cell-independent bead lesions produced the least amounts of IRAP. In draining lymphoid tissue the onset of IRAP production corresponded with local cell proliferation in both primary and secondary egg responses. Next, the in vivo role of IRAP was tested by administration of anti-IRAP antisera which caused 40-50% increases in egg granuloma area. Moreover, treatment increased (50-100%) IL-2, IL-4, IL-10, and IFN-gamma production in the primary response and all but IFN in secondary response lymph node cultures. Our results suggest that IRAP is an endogenous regulatory protein and may limit the activity of IL-1 during the Ag-specific granulomatous response to schistosome eggs. Furthermore, our findings provide in vivo support for the notion that Ag-elicited lymphocyte-derived products probably augment IRAP production and block the action of IL-1.
本研究检测了白细胞介素-1受体拮抗剂蛋白（IRAP）在调节对血吸虫卵免疫/炎症反应中的作用。通过逆转录酶和引物导向的聚合酶链反应对IRAP特异性mRNA转录本进行初步筛选，结果表明，在曼氏血吸虫卵诱导的超敏反应性肉芽肿的肺组织中有显著的内源性IRAP合成，而在正常肺组织或非免疫性珠粒肉芽肿的肺组织中则没有。使用mIRAP特异性抗体进行的直接检测证实了RNA研究的结果。酶联免疫吸附测定（ELISA）和免疫组织化学研究均显示，在分离的卵肉芽肿和局部反应性淋巴组织培养物中有显著的自发性IRAP产生，其主要但并非仅局限于巨噬细胞。与原发性病变相比，同步发生的继发性血吸虫卵肉芽肿显示出IRAP产生加速且增加，这与肉芽肿细胞数量和生长动力学情况平行。非免疫性T细胞非依赖性珠粒病变产生的IRAP量最少。在引流淋巴组织中，IRAP产生的起始与原发性和继发性卵反应中的局部细胞增殖相对应。接下来，通过给予抗IRAP抗血清来测试IRAP在体内的作用，结果导致卵肉芽肿面积增加40%-50%。此外，在原发性反应中，治疗使白细胞介素-2（IL-2）、白细胞介素-4（IL-4）、白细胞介素-10（IL-10）和γ干扰素（IFN-γ）的产生增加（50%-100%），在继发性反应淋巴结培养物中，除IFN外所有这些细胞因子的产生均增加。我们的结果表明，IRAP是一种内源性调节蛋白，在对血吸虫卵的抗原特异性肉芽肿反应过程中可能会限制白细胞介素-1的活性。此外，我们的研究结果为以下观点提供了体内证据，即抗原引发的淋巴细胞衍生产物可能会增加IRAP的产生并阻断白细胞介素-！的作用。
