Human peptidoglycan recognition protein S is an effector of neutrophil-mediated innate immunity

Human peptidoglycan recognition protein S is an effector of neutrophil-mediated innate immunity
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DOI:
10.1182/blood-2005-02-0530
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发表时间:
2005-10-01
期刊:
影响因子:
20.3
通讯作者:
Ezekowitz, RAB
Ezekowitz, RAB
中科院分区:
医学1区
文献类型:
--
作者:
Cho, JH;Fraser, IP;Ezekowitz, RAB

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对细菌的先天免疫反应需要宿主识别分子和吞噬细胞之间的协同作用。肽聚糖识别蛋白(PGRP)是昆虫和哺乳动物中发现的一大类与细菌肽聚糖结合的蛋白质:PGRP-S与其他抗菌蛋白如溶菌酶一起位于人中性粒细胞颗粒中。而PGRP-S和。溶菌酶识别pGN,人pGRP-S的确切结合特异性,其功能活性,以及它与其他中性粒细胞来源的杀菌蛋白如溶菌酶的潜在协同作用尚未确定。结果表明,人PGRP-S结合并抑制金黄色葡萄球菌(含赖氨酸型pGN)和大肠杆菌(含中二氨基戊二酸型pGn)的生长。它的结合力、亲和力以及因此的抗菌活性。前列环素-S是由前列环素中的第三个氨基酸决定的。此外,pGRP-S对大肠杆菌的抗菌作用与溶菌酶具有协同作用,溶菌酶和pGRP-S共定位在中性粒细胞外陷阱(NETs)中,表明这些颗粒衍生蛋白共同作用于NETS中的细菌。综上所述,这些结果表明人类PG。反相S;在中性粒细胞背景下,通过杀灭细胞内和细胞外细菌,在先天免疫中发挥作用。
Innate immune responses to bacteria re quire cooperative interactions between host recognition molecules and phagocytes. The peptidoglycan recognition proteins (PGRPs) are a large group of proteins found in insects and mammals that bind to bacterial peptidoglycan (PGN): PGRP-S is located with other antimicrobial proteins, such as lysozyme, in the granules of human neutrophils. Whereas both PGRP-S and. lysozyme recognize PGN, the exact binding specificity of human PGRP-S, its functional activity, and its potential synergy with other neutrophil-derived bactericidal proteins such as lysozyme have not been determined. Herd we show that human PGRP-S binds to and inhibits the growth of Staphylococcus aureus (containing lysine-type PGN) and Escherichia coli (containing mesodiaminopimelic acid-type PGN). The binding, affinity and thus antimicrobial activity of. PGRP-S is determined by the third amino acid in, the PGN stem peptide. Furthermore, the antimicrobial effect of PGRP-S against E coli is synergistic with lysozyme, and lysozyme and PGRP-S colocalize in neutrophil extracellular traps (NETs), suggesting that these granule-derived proteins act together to kill bacteria trapped in the NETs. Taken together, these results indicate that human PG. RP-S; plays a role in innate immunity in the context of neutrophils by contributing to the killing of intracellular and extracellular bacteria.