The potent anti-Staphylococcus aureus activity of a sterile rabbit inflammatory fluid is due to a 14-kD phospholipase A2.

The potent anti-Staphylococcus aureus activity of a sterile rabbit inflammatory fluid is due to a 14-kD phospholipase A2.
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无菌兔炎症液的有效抗金黄色葡萄球菌活性归因于 14-kD 磷脂酶 A2。

DOI:
10.1172/jci118399
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发表时间:
1996
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Weiss,J
Weiss,J
中科院分区:
--
文献类型:
--
作者:
Weinrauch,Y;Elsbach,P;Madsen,LM;Foreman,A;Weiss,J

文献摘要

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在家兔中引起的无菌炎性腹膜渗出物的无细胞液(腹水,AF)对补体抵抗的革兰氏阴性和革兰氏阳性细菌种属具有强效杀菌作用。这种活性在血浆中不存在。我们现在表明,基本上所有的活动,在AF对金黄色葡萄球菌是由于第二组14-kD磷脂酶A2(PLA 2),以前在本实验室从AF纯化。纯化的PLA 2和含有相应量的PLA 2的完整AF的抗葡萄球菌活性相当,并且被抗AF-PLA 2血清阻断。在AF中存在的浓度(约10 nM)下,AF PLA 2杀死> 2 log的10(6)S。金黄色葡萄球菌/ml,包括耐甲氧西林的临床分离株和其它革兰氏阳性菌。人II型PLA 2对S.金黄色葡萄球菌(LD 90约1-5 nM),而来自猪胰腺和蛇毒的14-kD PLA 2即使在微摩尔剂量下也是无活性的。PLA 2杀死细菌需要Ca 2+和催化活性,并伴随着细菌磷脂分解和细菌细胞膜和细胞壁的破坏。这些发现表明,II组细胞外PLA 2,其在炎症部位的功能尚不清楚,是一种非常有效的内源性抗生素对S。金黄色葡萄球菌和其他革兰氏阳性菌。
The cell-free fluid (ascitic fluid, AF) of a sterile inflammatory peritoneal exudate elicited in rabbits is potently bactericidal for complement-resistant gram-negative as well as gram-positive bacterial species. This activity is absent in plasma. We now show that essentially all activity in AF against Staphylococcus aureus is attributable to a group II 14-kD phospholipase A2 (PLA2), previously purified from AF in this laboratory. Antistaphylococcal activity of purified PLA2 and of whole AF containing a corresponding amount of PLA2 was comparable and blocked by anti-AF-PLA2 serum. At concentrations present in AF (approximately 10 nM), AF PLA2 kills > 2 logs of 10(6) S. aureus/ml, including methicillin-resistant clinical isolates, and other species of gram-positive bacteria. Human group II PLA2 displays similar bactericidal activity toward S. aureus (LD90 approximately 1-5 nM), whereas 14-kD PLA2 from pig pancreas and snake venom are inactive even at micromolar doses. Bacterial killing by PLA2 requires Ca2+ and catalytic activity and is accompanied by bacterial phospholipolysis and disruption of the bacterial cell membrane and cell wall. These findings reveal that group II extracellular PLA2, the function of which at inflammatory sites has been unclear, is an extraordinarily potent endogenous antibiotic against S. aureus and other gram-positive bacteria.