Bovine peptidoglycan recognition protein-S: Antimicrobial activity, localization, secretion, and binding properties
Bovine peptidoglycan recognition protein-S: Antimicrobial activity, localization, secretion, and binding properties
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DOI：
10.4049/jimmunol.176.2.1154
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发表时间：
2006-01-15
影响因子：
4.4
通讯作者：
Selsted, ME
中科院分区：
文献类型：
--
作者：
Tydell, CC;Yuan, J;Selsted, ME
肽聚糖（PGN）识别蛋白（PGRPs）是先天免疫的模式识别分子，从昆虫到人类都是保守的。据报道，各种pgrp具有不同的功能：它们结合细菌分子，消化PGN，并且对果蝇的Toll通路至关重要。一个家族成员牛PGN识别蛋白s （bPGRP-S）被发现以不依赖于PGN的方式结合和杀死微生物，这引起了对bPGRP-S配体身份的质疑。为了解决这个问题，我们已经确定了bPGRP-S在一系列近似生理条件的溶液中的结合和杀微生物特性。在这项研究中，我们发现bPGRP-S与其他细菌成分，包括脂多糖和脂磷壁酸，具有比PCP更高的亲和力，这是由它们抑制bPGRP-S介导的细菌杀伤能力决定的。pgrp在体内的作用位置和方式尚不清楚。通过免疫金电镜，PGRP-S定位于含有这些细胞的氧不依赖性杀菌蛋白的致密/大颗粒中性粒细胞和中性粒细胞吞噬溶酶体。此外，免疫金染色和分泌研究表明，中性粒细胞暴露于细菌时分泌PGRP-S。牛PGRP-S能介导热死菌的直接裂解；然而，pgrp - s介导的细菌杀伤不依赖于这种活性。bPGRP-S具有多种活性和对几种细菌分子的亲和力的证据挑战了PGRP蛋白家族概括tlr进化的假设。哺乳动物的pgrp对一小部分目标生物没有单一的抗菌活性；相反，他们在亲和力和活动性上都是多面手。
Peptidoglycan (PGN) recognition proteins (PGRPs) are pattern recognition molecules of innate immunity that are conserved from insects to humans. Various PGRPs are reported to have diverse functions: they bind bacterial molecules, digest PGN, and are essential to the Toll pathway in Drosophila. One family member, bovine PGN recognition protein-S (bPGRP-S), has been found to bind and kill microorganisms in a PGN-independent manner, raising questions about the identity of the bPGRP-S ligand. Addressing this, we have determined the binding and microbicidal properties of bPGRP-S in a range of solutions approximating physiologic conditions. In this study we show that bPGRP-S interacts with other bacterial components, including LPS and lipoteichoic acid, with higher affinities than for PCP, as determined by their abilities to inhibit bPGRP-S-mediated killing of bacteria. Where and how PGRPs act in vivo is not yet clear. Using Immunogold electron microscopy, PGRP-S was localized to the dense/large granules of naive neutrophils, which contain the oxygen-independent bactericidal proteins of these cells, and to the neutrophil phagolysosome. In addition, Immunogold staining and secretion studies demonstrate that neutrophils secrete PGRP-S when exposed to bacteria. Bovine PGRP-S can mediate direct lysis of heat-killed bacteria; however, PGRP-S-mediated killing of bacteria is independent of this activity. Evidence that bPGRP-S has multiple activities and affinity to several bacterial molecules challenges the assumption that the PGRP family of proteins recapitulates the evolution of TLRs. Mammalian PGRPs do not have a single antimicrobial activity against a narrow range of target organisms; rather, they are generalists in their affinity and activity.