Canque B, Rosenzwajg M, Gey A, Tartour E, Fridman W H, Gluckman J C
Laboratoire de Biologie et Génétique des Déficits Immunitaires, faculté de Médecine and hôpital de la Pitié-Salpétrière, Paris, France.
Blood. 1996 Mar 1;87(5):2011-9.
Disparate findings have been reported as to whether human immunodeficiency virus (HIV) affects cytokine production by macrophages (MA). We investigated production of different cytokines and of macrophage inflammatory protein (MIP)-1alpha by HIV-1Ba-L- or HIV-1Ada-infected blood-derived MA. Relative to controls, only MIP-1alpha levels increased twofold to > 10-fold in supernatants 2 to 3 weeks postinfection (PI), at the time of maximum virus production; levels of the other chemokines (RANTES, interleukin (IL)-8) and cytokines (IL-1alpha, IL-3, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1) investigated were not affected. MIP-1alpha mRNA signal assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) was, however, only occasionally greater in cells from infected cultures relative to controls. MIP-1alpha levels in supernatants remained in the same range as in control cultures when more than 10 mmol/L Zidovudine was added 24 hours PI, which indicates involvement of virus replication in the effect. Anti-MIP-1alpha antibody labeling identified a 10% to 25% subset of MA, strongly expressing HLA-DR and CD4, and also stained by anti-IL-6 and anti-TNF-alpha antibodies. Two weeks PI, dual staining showed that the majority of the 5% to 20% cells that were p24+ belonged to the MIP-1alpha+ population, which may define a MA subset capable to better sustain HIV replication. MIP-1alpha induced by HIV replication in MA might play a role in the pathophysiology of HIV infection; in impaired hematopoiesis; or as a CD4+ and CD8+ lymphocyte chemoattractant, by recruiting either or both HIV-susceptible and cytotoxic T lymphocytes to virus replication sites.
关于人类免疫缺陷病毒（HIV）是否影响巨噬细胞（MA）产生细胞因子，已有不同的研究结果报道。我们研究了HIV-1Ba-L或HIV-1Ada感染的血液来源巨噬细胞产生不同细胞因子及巨噬细胞炎性蛋白（MIP）-1α的情况。与对照组相比，仅在感染后（PI）2至3周，即病毒产生量最高时，上清液中的MIP-1α水平增加了两倍至超过10倍；所研究的其他趋化因子（RANTES、白细胞介素（IL）-8）和细胞因子（IL-1α、IL-3、IL-6、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、G-CSF、肿瘤坏死因子（TNF）-α、转化生长因子（TGF）-β1）水平未受影响。然而，通过逆转录聚合酶链反应（RT-PCR）评估的MIP-1α mRNA信号，相对于对照组，仅在感染培养细胞中偶尔更高。感染后24小时加入超过10 mmol/L齐多夫定，上清液中的MIP-1α水平仍与对照培养物中的水平处于同一范围，这表明病毒复制参与了该效应。抗MIP-1α抗体标记鉴定出10%至25%的巨噬细胞亚群，其强烈表达HLA-DR和CD4，并且也被抗IL-6和抗TNF-α抗体染色。感染后两周，双重染色显示，5%至20%的p24+细胞中的大多数属于MIP-1α+群体，这可能定义了一个能够更好维持HIV复制的巨噬细胞亚群。HIV在巨噬细胞中复制诱导的MIP-1α可能在HIV感染的病理生理学中发挥作用；在造血功能受损中发挥作用；或者作为CD4+和CD8+淋巴细胞趋化因子，通过募集HIV易感和细胞毒性T淋巴细胞中的一种或两种到病毒复制部位发挥作用。
