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人类免疫缺陷病毒蛋白酶抑制剂对中性粒细胞凋亡的体外和体内作用

Ex vivo and in vitro effect of human immunodeficiency virus protease inhibitors on neutrophil apoptosis.

作者信息

Mastroianni C M, Mengoni F, Lichtner M, D'Agostino C, d'Ettorre G, Forcina G, Marzi M, Russo G, Massetti A P, Vullo V

机构信息

Department of Infectious and Tropical Diseases, La Sapienza University, Rome, Italy.

出版信息

J Infect Dis. 2000 Nov;182(5):1536-9. doi: 10.1086/315858. Epub 2000 Oct 9.

DOI:10.1086/315858
PMID:11023478
Abstract

Polymorphonuclear leukocytes (PMNL) from human immunodeficiency virus (HIV)-infected patients exhibit accelerated apoptosis and impaired functional activity. HIV protease inhibitor-based therapy produces improvements in both acquired and innate immune responses. Ex vivo and in vitro effects of HIV protease inhibitors on apoptosis and chemotaxis of PMNL were evaluated. After therapy, there was a rapid and significant decrease of PMNL apoptosis, which correlated with increased chemotactic function. These findings were found both in patients with immunological and virological response and in control subjects who showed an increase in CD4(+) T cell counts but no concomitant decline in HIV load. After in vitro treatment with ritonavir or indinavir, apoptosis of both HIV-infected and -uninfected PMNL markedly decreased and correlated with significant enhancement of chemotaxis. These results suggest that HIV protease inhibitors may improve the PMNL function by reducing the apoptosis rate and that this effect may, at least in part, be independent of their antiviral activity.

摘要

来自人类免疫缺陷病毒(HIV)感染患者的多形核白细胞(PMNL)表现出加速凋亡和功能活性受损。基于HIV蛋白酶抑制剂的疗法可使获得性免疫反应和先天性免疫反应均得到改善。评估了HIV蛋白酶抑制剂对PMNL凋亡和趋化性的体外和体内效应。治疗后,PMNL凋亡迅速且显著减少,这与趋化功能增强相关。在有免疫和病毒学反应的患者以及CD4(+) T细胞计数增加但HIV载量无相应下降的对照受试者中均发现了这些结果。在用利托那韦或茚地那韦进行体外治疗后,HIV感染和未感染的PMNL的凋亡均显著减少,且与趋化性的显著增强相关。这些结果表明,HIV蛋白酶抑制剂可能通过降低凋亡率来改善PMNL功能,并且这种作用可能至少部分独立于其抗病毒活性。

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