von der Möhlen M A, van der Poll T, Jansen J, Levi M, van Deventer S J
Academic Medical Center, Laboratory of Experimental Internal Medicine, University of Amsterdam, Amsterdam, The Netherlands.
J Immunol. 1996 Jun 15;156(12):4969-73.
Bactericidal/permeability-increasing protein (BP]) is contained within the azurophilic granules of neutrophils and is able to neutralize endotoxin and kill Gram-negative bacteria. TNF has been implicated as a mediator of endotoxin-induced neutrophil degranulation. To assess the role of TNF in the elevated BPI levels during sepsis, the following studies were performed. 1) In 31 consecutive patients with sepsis syndrome, plasma BPI levels were markedly elevated compared with those in healthy controls, but showed no correlation with simultaneously measured TNF concentrations. 2) In four healthy men, i.v. injection of recombinant human TNF (50 microg/m2) induced a rapid rise in plasma BPI levels. 3) In eight normal subjects, i.v. administration of Escherichia coli endotoxin (4 ng/kg) elicited subsequent increases in the plasma concentrations of TNF and BPI. 4) Eight healthy chimpanzees were investigated after i.v. injection of endotoxin (4 ng/kg); four animals received endotoxin only, and four animals received an anti-TNF mAb simultaneously. Although anti-TNF completely prevented the endotoxin-induced appearance of TNF activity, the rise in BPI levels remained unaltered. These results suggest that TNF is not critical for the release of BPI from neutrophils during experimental endotoxemia or clinical sepsis.
杀菌/通透性增加蛋白（BPI）存在于中性粒细胞的嗜天青颗粒中，能够中和内毒素并杀死革兰氏阴性菌。肿瘤坏死因子（TNF）被认为是内毒素诱导的中性粒细胞脱颗粒的介质。为了评估TNF在脓毒症期间BPI水平升高中的作用，进行了以下研究。1）在31例连续的脓毒症综合征患者中，血浆BPI水平与健康对照组相比明显升高，但与同时测量的TNF浓度无相关性。2）在4名健康男性中，静脉注射重组人TNF（50μg/m²）导致血浆BPI水平迅速升高。3）在8名正常受试者中，静脉注射大肠杆菌内毒素（4ng/kg）引起随后血浆中TNF和BPI浓度的升高。4）8只健康黑猩猩在静脉注射内毒素（4ng/kg）后接受研究；4只动物仅接受内毒素，4只动物同时接受抗TNF单克隆抗体。尽管抗TNF完全阻止了内毒素诱导的TNF活性出现，但BPI水平的升高仍未改变。这些结果表明，在实验性内毒素血症或临床脓毒症期间，TNF对于中性粒细胞释放BPI并不关键。
