Whitten Miranda M A, Tew Ian F, Lee Bok L, Ratcliffe Norman A
Biomedical and Physiological Research Group, School of Biological Sciences, University of Wales Swansea, Swansea, United Kingdom.
J Immunol. 2004 Feb 15;172(4):2177-85. doi: 10.4049/jimmunol.172.4.2177.
Lipoproteins and molecules for pattern recognition are centrally important in the innate immune response of both vertebrates and invertebrates. Mammalian apolipoproteins such as apolipoprotein E (apoE) are involved in LPS detoxification, phagocytosis, and possibly pattern recognition. The multifunctional insect protein, apolipophorin III (apoLp-III), is homologous to apoE. In this study we describe novel roles for apoLp-III in pattern recognition and multicellular encapsulation reactions in the innate immune response, which may be of direct relevance to mammalian systems. It is known that apoLp-III stimulates antimicrobial peptide production in insect blood, enhances phagocytosis by insect blood cells (hemocytes), and binds and detoxifies LPS and lipoteichoic acid. In the present study we show that apoLp-III from the greater wax moth, Galleria mellonella, also binds to fungal conidia and beta-1,3-glucan and therefore may act as a pattern recognition molecule for multiple microbial and parasitic invaders. This protein also stimulates increases in cellular encapsulation of nonself particles by the blood cells and exerts shorter term, time-dependent, modulatory effects on cell attachment and spreading. All these responses are dose dependent, occur within physiological levels, and, with the notable exception of beta-glucan binding, are only observed with the lipid-associated form of apoLp-III. Preliminary studies also established a beneficial role for apoLp-III in the in vivo response to an entomopathogenic fungus. These data suggest a wide range of immune functions for a multiple specificity pattern recognition molecule and may provide a useful model for identifying further potential roles for homologous proteins in mammalian immunology, particularly in terms of fungal infections, pneumoconiosis, and granulomatous reactions.
脂蛋白和模式识别分子在脊椎动物和无脊椎动物的先天性免疫反应中都至关重要。哺乳动物载脂蛋白，如载脂蛋白E（apoE），参与脂多糖解毒、吞噬作用，并可能参与模式识别。多功能昆虫蛋白载脂蛋白III（apoLp-III）与apoE同源。在本研究中，我们描述了apoLp-III在先天性免疫反应中的模式识别和多细胞包囊反应中的新作用，这可能与哺乳动物系统直接相关。已知apoLp-III能刺激昆虫血液中抗菌肽的产生，增强昆虫血细胞（血细胞）的吞噬作用，并结合脂多糖和脂磷壁酸并使其解毒。在本研究中，我们表明，大蜡螟（Galleria mellonella）的apoLp-III也能与真菌分生孢子和β-1,3-葡聚糖结合，因此可能作为多种微生物和寄生虫入侵者的模式识别分子。这种蛋白质还能刺激血细胞对非自身颗粒的细胞包囊增加，并对细胞附着和铺展产生短期、时间依赖性的调节作用。所有这些反应都是剂量依赖性的，发生在生理水平内，并且，除了β-葡聚糖结合外，只有与脂质相关形式的apoLp-III才能观察到。初步研究还确定了apoLp-III在体内对昆虫病原真菌反应中的有益作用。这些数据表明，一种具有多种特异性的模式识别分子具有广泛的免疫功能，并可能为确定同源蛋白在哺乳动物免疫学中的进一步潜在作用提供一个有用的模型，特别是在真菌感染、尘肺病和肉芽肿反应方面。
