Mobilization of potent plasma bactericidal activity during systemic bacterial challenge. Role of group IIA phospholipase A2.

Mobilization of potent plasma bactericidal activity during systemic bacterial challenge. Role of group IIA phospholipase A2.
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在全身细菌攻击期间动员有效的血浆杀菌活性。

DOI:
10.1172/jci3121
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发表时间:
1998
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;Abad,C;Liang,NS;Lowry,SF;Weiss,J

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糖原诱导的兔炎性腹膜渗出液中IIA组14-kD磷脂酶A2 (PLA2)的细胞外动员是炎症液对金黄色葡萄球菌具有强效杀菌活性的原因(1996)。j .中国。投资。97:250 - 257)。由于在全身性炎症期间血浆中诱导了相似水平的PLA2,我们已经测试了这是否会引起静息动物中不存在的血浆杀菌活性。将致死剂量的大肠杆菌静脉注射给狒狒,在注射前和注射后每隔一小时采集一次血浆或血清。注射细菌后,血浆和血清中的PLA2水平在24小时内上升了100倍,达到约1微克PLA2/ml。24小时收集的血清对金黄色葡萄球菌、化脓性链球菌和被封装的大肠杆菌具有有效的杀菌活性,而从未挑战的动物收集的血清中没有表现出这种活性。对金黄色葡萄球菌和化脓性葡萄球菌的杀菌活性几乎完全被人IIA PLA2组的单克隆抗体阻断,纯化的人IIA PLA2组添加到攻毒前血清中,其抗葡萄球菌和抗链球菌活性与攻毒后24 h的血清相当。pla2依赖性杀菌活性通过组成性存在于血清或血浆中的因子提高约10倍。对被包裹的大肠杆菌的杀菌活性伴随着广泛的细菌磷脂降解,至少部分是由动员的IIA PLA2介导的,但取决于24小时血清中其他杀菌因子的作用。这些发现进一步证明了IIA PLA2对生物体液的抗菌效力的贡献,并提示炎症期间该酶的动员可能在宿主防御入侵细菌方面发挥重要作用。
Extracellular mobilization of Group IIA 14-kD phospholipase A2 (PLA2) in glycogen-induced rabbit inflammatory peritoneal exudates is responsible for the potent bactericidal activity of the inflammatory fluid toward Staphylococcus aureus (1996. J. Clin. Invest. 97:250-257). Because similar levels of PLA2 are induced in plasma during systemic inflammation, we have tested whether this gives rise to plasma bactericidal activity not present in resting animals. Baboons were injected intravenously (i.v.) with a lethal dose of Escherichia coli and plasma or serum was collected before and at hourly intervals after injection. After infusion of bacteria, PLA2 levels in plasma and serum rose > 100-fold over 24 h to approximately 1 microg PLA2/ml. Serum collected at 24 h possessed potent bactericidal activity toward S. aureus, Streptococcus pyogenes, and encapsulated E. coli not exhibited by serum collected from unchallenged animals. Bactericidal activity toward S. aureus and S. pyogenes was nearly completely blocked by a monoclonal antibody to human Group IIA PLA2 and addition of purified human Group IIA PLA2 to prechallenge serum conferred potent antistaphylococcal and antistreptococcal activity equal to that of the 24 h post-challenge serum. PLA2-dependent bactericidal activity was enhanced approximately 10x by factor(s) present constitutively in serum or plasma. Bactericidal activity toward encapsulated E. coli was accompanied by extensive bacterial phospholipid degradation mediated, at least in part, by the mobilized Group IIA PLA2 but depended on the action of other bactericidal factors in the 24-h serum. These findings further demonstrate the contribution of Group IIA PLA2 to the antibacterial potency of biological fluids and suggest that mobilization of this enzyme during inflammation may play an important role in host defense against invading bacteria.
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DOI: --
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影响因子: 2.4
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影响因子: --
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