Involvement of the acute phase protein α1-acid glycoprotein in nonspecific resistance to a lethal Gram-negative infection
Involvement of the acute phase protein α1-acid glycoprotein in nonspecific resistance to a lethal Gram-negative infection
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DOI：
10.1074/jbc.275.20.14903
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发表时间：
2000-05-19
影响因子：
4.8
通讯作者：
Libert, C
中科院分区：
文献类型：
--
作者：
Hochepied, T;Van Molle, W;Libert, C
对革兰氏阴性感染的抵抗力可以通过用松节油和白介素1等多种药剂对动物进行预处理来诱导。因为这些药物是急性时相蛋白的强大诱导剂，我们想知道这些蛋白，尤其是α(1)-酸性糖蛋白(α(1)-AGP)是否参与了对感染的非特异性抵抗。松节油和IL-1分别在肺炎克雷伯菌致死攻击前48小时和12-48小时给药，可完全保护肺炎克雷伯菌免受攻击。血清Alpha(1)-AGP在松节油注射后48h和IL-1注射后12~48h达到峰值。肺炎前2小时给予RW-AGP可显著提高小鼠的存活率。经松节油、IL-1或α(1)-AGP保护剂量处理的小鼠血液和器官培养的细菌数量显著减少，这些数据表明，α(1)-AGP可能是松节油或IL-1诱导的保护作用的媒介，因为松节油或IL-1最大诱导α(1)-AGP的时间点与α(1)-AGP最佳保护的时间点一致。转基因过表达的大鼠α(1)-agp可保护小鼠免受肺炎衣原体感染。转基因小鼠血液和器官中的细菌数量显著减少，只有对照组小鼠脾内出现大片坏死区、细胞凋亡和血块。我们的数据表明，α(1)-AGP可以预防革兰氏阴性感染，可能是非特异性感染抵抗的重要组成部分。
Resistance to Gram-negative infection can be induced by pretreating animals with several agents such as turpentine and interleukin (IL)-1. Because these agents are powerful inducers of acute phase proteins, we wondered whether these proteins, more particularly alpha(1)-acid glycoprotein (alpha(1)-AGP), are involved in nonspecific resistance to infection. Turpentine and IL-1 protect completely against a lethal challenge of Klebsiella pneumoniae when given 48 and 12-48 h before the challenge, respectively. alpha(1)-AGP induction in the serum reached peak values 48 h after turpentine and 12-48 h after IL-1 injection. Administration of rw,-AGP, 2 h before a challenge of It pneumoniae, significantly increased the survival. Numbers of bacteria cultured from blood and organs were significantly lower in mice pretreated with a protective dose of turpentine, IL-1, or alpha(1)-AGP, These data suggest that alpha(1)-AGP is a possible mediator in turpentine- or IL-1-induced protection because time points of maximal induction of alpha(1)-AGP by turpentine or IL-1 and of optimal protection by alpha(1)-AGP coincide. Transgenic overexpression of rat alpha(1)-AGP protected mice from a It pneumoniae infection. Bacterial counts in blood and organs were significantly lower in transgenic mice, and only in control mice were large necrotic areas, apoptosis, and blood clots observed in the spleen. Our data suggest that alpha(1)-AGP prevents Gram-negative infections and may be an essential component in nonspecific resistance to infection.