Mammalian peptidoglycan recognition protein binds peptidoglycan with high affinity, is expressed in neutrophils, and inhibits bacterial growth
Mammalian peptidoglycan recognition protein binds peptidoglycan with high affinity, is expressed in neutrophils, and inhibits bacterial growth
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DOI：
10.1074/jbc.m001239200
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发表时间：
2000-08-11
影响因子：
4.8
通讯作者：
Dziarski, R
中科院分区：
文献类型：
--
作者：
Liu, C;Gelius, E;Dziarski, R
肽聚糖识别蛋白（PGRP）是一种从昆虫到哺乳动物都很保守的蛋白质。在昆虫中，PGRP识别细菌细胞壁肽聚糖（PGN）并激活酚氧化酶原级联，这是昆虫抗菌防御系统的一部分。由于哺乳动物没有酚氧化酶原级联反应，其在哺乳动物中的功能尚不清楚。然而，有人建议，相同的蛋白质（Tag7）是一种肿瘤坏死因子样细胞因子。因此，本研究的目的是确定PGRP在哺乳动物中的功能。小鼠PGRP以快速动力学和纳摩尔亲和力（Kd = 13 nM）结合PGN。结合是特异性的聚合物PGN或革兰氏阳性细菌与未修饰的PGN，和PGRP不结合其他细胞壁成分或革兰氏阴性细菌。PGRP mRNA和蛋白在中性粒细胞和骨髓细胞中表达，而在脾细胞、单核细胞、T或B淋巴细胞、NK细胞、胸腺细胞、单核细胞和巨噬细胞中不表达。PGRP不是PGN裂解酶或溶菌酶，但它抑制革兰氏阳性菌而不是革兰氏阴性菌的生长。PGRP抑制巨噬细胞对革兰氏阳性菌的吞噬作用，抑制中性粒细胞中革兰氏阳性菌诱导的氧化爆发，抑制巨噬细胞中PGN诱导的细胞因子产生。PGRP对哺乳动物细胞无肿瘤坏死因子样细胞毒性，其本身或与PGN组合均无趋化性。因此，哺乳动物PGRP以纳摩尔亲和力结合PGN和革兰氏阳性细菌，在嗜中性粒细胞中表达，并抑制细菌生长。
Peptidoglycan recognition protein (PGRP) is conserved from insects to mammals. In insects, PGRP recognizes bacterial cell wall peptidoglycan (PGN) and activates prophenoloxidase cascade, a part of the insect antimicrobial defense system. Because mammals do not have the prophenoloxidase cascade, its function in mammals is unknown. However, it was suggested that an identical protein (Tag7) was a tumor necrosis factor-like cytokine. Therefore, the aim of this study was to identify the function of PGRP in mammals. Mouse PGRP bound to PGN with fast kinetics and nanomolar affinity (K-d = 13 nM). The binding was specific for polymeric PGN or Gram-positive bacteria with unmodified PGN, and PGRP did not bind to other cell wall components or Gram-negative bacteria. PGRP mRNA and protein were expressed in neutrophils and bone marrow cells, but not in spleen cells, mononuclear cells, T or B lymphocytes, NK cells, thymocytes, monocytes, and macrophages. PGRP was not a PGN-lytic or a bacteriolytic enzyme, but it inhibited the growth of Gram-positive but not Gramnegative bacteria. PGRP inhibited phagocytosis of Gram-positive bacteria by macrophages, induction of oxidative burst by Gram-positive bacteria in neutrophils, and induction of cytokine production by PGN in macrophages. PGRP had no tumor necrosis factor-like cytotoxicity for mammalian cells, and it was not chemotactic on its own or in combination with PGN. Therefore, mammalian PGRP binds to PGN and Gram-positive bacteria with nanomolar affinity, is expressed in neutrophils, and inhibits growth of bacteria.