EXTRACELLULAR ACCUMULATION OF POTENTLY MICROBICIDAL BACTERICIDAL PERMEABILITY-INCREASING PROTEIN AND P15S IN AN EVOLVING STERILE RABBIT PERITONEAL INFLAMMATORY EXUDATE
EXTRACELLULAR ACCUMULATION OF POTENTLY MICROBICIDAL BACTERICIDAL PERMEABILITY-INCREASING PROTEIN AND P15S IN AN EVOLVING STERILE RABBIT PERITONEAL INFLAMMATORY EXUDATE
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DOI：
10.1172/jci117873
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发表时间：
1995-04-01
影响因子：
15.9
通讯作者：
WEISS, J
中科院分区：
文献类型：
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作者：
WEINRAUCH, Y;FOREMAN, A;WEISS, J
PMN的颗粒相关抗菌蛋白和肽的宿主防御作用在多大程度上包括细胞外作用尚未确定。为了解决这个问题，我们分析了从糖原诱导的无菌炎性兔腹膜渗出物获得的无细胞（腹水）液（AP）的抗菌活性，其中> 95%的积聚细胞是PMN、AF，而不是平行收集的血浆，对血清抗性革兰氏阴性和革兰氏阳性细菌表现出有效的活性，在注射糖原后的前12小时期间，AF的总抗菌活性和比抗菌活性与PMN的流入平行地增加，在30分钟/ml的AF中，最多> 99%的10（7）包封的大肠杆菌和金黄色葡萄球菌被杀死，中性粒细胞的杀菌/通透性增加蛋白（BPI）的中和抗体消除AF对包囊E。而单独使用BPI（相当于AF中1 μ g/ml）仅能使AF对大肠杆菌的活性小于或等于20%。AF还含有与BPI协同作用的15 kD PMN蛋白（p15 s），AF中存在的量的纯化的BPI和p15 s重建AF对包封的E. coli的生长抑制活性。这些发现首次显示了内源性BPI的细胞外功能，与p15一起提供了针对对血浆来源蛋白和炎症渗出物中吞噬细胞耐药的革兰氏阴性菌的有效杀微生物系统。
To what extent the host defense role of granule-associated antibacterial proteins and peptides of PMN includes extracellular action has not been established, To address this question, we have analyzed the antibacterial activity of cell-free (ascitic) fluid (AP) obtained from glycogen-induced sterile inflammatory rabbit peritoneal exudates in which > 95% of the accumulating cells are PMN, AF, but not plasma collected in parallel, exhibits potent activity toward serum-resistant Gram-negative and Gram-positive bacteria, Total and specific antibacterial activity of AF increases during the first 12 h after injection of glycogen in parallel with the influx of PMN, At maximum, > 99 % of 10(7) encapsulated Escherichia coli and Staphylococcus aureus are killed in 30 min/ml of AF, Neutralizing antibodies against the bactericidal/permeability-increasing protein (BPI) of PMN abolishes activity of AF toward encapsulated E. coli but has no effect on activity vs staphylococci, However, BPI alone(similar to 1 mu g/ml in AF) can only account for less than or equal to 20% of AF activity toward E. coli, AF also contains 15 kD PMN proteins (p15s) that act in synergy with BPI, Purified BPI and p15s, in amounts present in AF, reconstitute the growth-inhibitory activity of AF toward encapsulated E. coli, These findings show for the first time an extracellular function of endogenous BPI, providing, together with the p15s, a potent microbicidal system toward Gram-negative bacteria resistant to plasma-derived proteins and phagocytes in inflammatory exudates.