Kotwal G J, Miller C G, Justus D E
Department of Microbiology and Immunology, University of Louisville School of Medicine, KY 40292, USA.
Mol Cell Biochem. 1998 Aug;185(1-2):39-46. doi: 10.1023/a:1006844624825.
Vaccinia virus (VV) and other pathogenic poxviruses encode for a complement control protein. The VV complement control protein or VCP, was one of the first soluble microbial proteins postulated to have an active role in the immunomodulation of the host defense. Since then, 2 other poxviruses, including variola virus and cowpox virus (CPV), were found to have corresponding proteins. Based upon earlier studies which demonstrated the role of the CPV complement control protein in modulating the specific tissue responses in BALB/c and congenic-matched C5-sufficient and C5-deficient mice, the CPV equivalent has been renamed the inflammation modulatory protein (IMP), so as to specifically reflect its function. In this study, the in vivo cellular response of mice injected with CPV or a recombinant virus lacking the IMP sequence (CPV-IMP) was examined using a connective tissue air pouch model. Microscopic examination revealed that CPV-IMP caused a significant mononuclear cell infiltration into the connective tissue and adjacent dermal tissue of the skin. To characterize IMP's ability to regulate the observed cellular infiltration through both complement derived and non-complement derived chemotactic factors, footpad and skin connective tissue of C3 knockout mice and footpad of MIP-1alpha knockout mice received injections of CPV and CPV-IMP. In comparison to the matched control, significantly greater footpad specific swelling response was seen in C3 -/- mice injected with CPV. This indicates an important role for C3 in poxvirus pathogenesis. However, MIP-1 alpha -/- mice injected with CPV-IMP recovered earlier than mice injected with CPV alone. This indicates that the function of IMP in vivo in mice with a complete repertoire of immune components is to limit cellular infiltration by down regulating the complement derived chemotactic analphylotoxins, thereby modulating the inflammatory response contributing to a diminished tissue pathology and preservation of viral habitat.
痘苗病毒（VV）和其他致病性痘病毒编码一种补体控制蛋白。痘苗病毒补体控制蛋白或VCP，是最早被假定在宿主防御免疫调节中发挥积极作用的可溶性微生物蛋白之一。从那时起，又发现另外两种痘病毒，包括天花病毒和牛痘病毒（CPV），也有相应的蛋白。基于早期研究表明CPV补体控制蛋白在调节BALB/c以及同基因匹配的C5充足和C5缺陷小鼠的特定组织反应中的作用，CPV的等效物已被重新命名为炎症调节蛋白（IMP），以便具体反映其功能。在本研究中，使用结缔组织气袋模型检查了注射CPV或缺乏IMP序列的重组病毒（CPV-IMP）的小鼠的体内细胞反应。显微镜检查显示，CPV-IMP导致单核细胞显著浸润到皮肤的结缔组织和相邻真皮组织中。为了表征IMP通过补体衍生和非补体衍生的趋化因子调节观察到的细胞浸润的能力，给C3基因敲除小鼠的足垫和皮肤结缔组织以及MIP-1α基因敲除小鼠的足垫注射CPV和CPV-IMP。与匹配的对照相比，注射CPV的C3 -/-小鼠出现了明显更大的足垫特异性肿胀反应。这表明C3在痘病毒发病机制中起重要作用。然而，注射CPV-IMP的MIP-1α -/-小鼠比单独注射CPV的小鼠恢复得更早。这表明IMP在具有完整免疫成分的小鼠体内的功能是通过下调补体衍生的趋化过敏毒素来限制细胞浸润，从而调节炎症反应，减轻组织病理学变化并保护病毒生存环境。
