HIV-1 gp120 Stimulates the Production of β-Chemokines in Human Peripheral Blood Monocytes Through a CD4-Independent Mechanism1
HIV-1 gp120 Stimulates the Production of β-Chemokines in Human Peripheral Blood Monocytes Through a CD4-Independent Mechanism1
复制标题
HIV-1 gp120 通过 CD4 独立机制刺激人外周血单核细胞产生 β-趋化因子1
作者：
L. Fantuzzi;I. Canini;F. Belardelli;S. Gessani
本研究旨在探讨HIV-1包膜糖蛋白gp 120对单核/巨噬细胞β-趋化因子表达的影响。用重组gp 120-IIIB处理新鲜分离的1天培养的单核细胞或7天培养的单核细胞衍生的巨噬细胞（MDM），导致单核细胞趋化蛋白-1、巨噬细胞炎性蛋白-1 β和RANTES的分泌特异性和剂量依赖性增强，以及转录物积累的明显增加。这些mRNA的表达增加，但不superinduced，放线菌酮的存在下。将单核细胞培养物暴露于gp 120-JRFL和醛硫醇-2-灭活的R5和X4 HIV-1菌株后，也诱导β-趋化因子分泌，保留包膜蛋白的构象和功能完整性。相比之下，X4和R5 gp 120或醛硫醇-2-灭活病毒处理对LPS完全应答的单核细胞样细胞系，未触发β-趋化因子分泌。gp 120介导的作用与其与CD 4的相互作用无关，因为与可溶性CD 4预孵育并不能消除β-趋化因子的诱导。此外，通过特异性Ab触发CD 4受体不会导致任何β-趋化因子分泌。有趣的是，特异性抗体与CCR 5和CXCR 4受体的结合以及用CCR 5和CXCR 4配体处理诱导β-趋化因子分泌。总体而言，这些结果表明HIV-1通过gp 120与细胞膜上的HIV-1辅助受体的特异性相互作用刺激单核细胞/巨噬细胞产生β-趋化因子。这些相关多肽的表达可能代表了调节病毒感染程度和免疫细胞募集的重要细胞应答。
The present study was designed to evaluate the effect of the HIV-1 envelope glycoprotein gp120 on the expression of β-chemokines in cultured monocytes/macrophages. Treatment of either freshly isolated 1-day-cultured monocytes or 7-day-cultured monocyte-derived macrophages (MDM) with recombinant gp120-IIIB resulted in a specific and dose-dependent enhancement of secretion of monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, and RANTES as well as a clear-cut increase in transcript accumulation. The expression of these mRNA was increased, but not superinduced, in the presence of cycloheximide. β-Chemokine secretion was also induced after exposure of monocyte cultures to gp120-JRFL and aldrithiol-2-inactivated R5 and X4 HIV-1 strains, retaining conformational and functional integrity of envelope proteins. In contrast, no β-chemokine secretion was triggered by X4 and R5 gp120 or aldrithiol-2-inactivated virus treatment of monocytoid cell lines that were fully responsive to LPS. The gp120-mediated effect was independent of its interaction with CD4, as preincubation with soluble CD4 did not abrogate β-chemokine induction. Moreover, triggering of CD4 receptor by a specific Ab did not result in any β-chemokine secretion. Interestingly, engagement of CCR5 and CXCR4 receptors by specific Abs as well as treatment with CCR5 and CXCR4 ligands induced β-chemokine secretion. On the whole, these results indicate that HIV-1 stimulates monocytes/macrophages to produce β-chemokines by a specific interaction of gp120 with HIV-1 coreceptors on the cell membrane. The expression of these related polypeptides may represent an important cellular response for regulating both the extent of viral infection and the recruitment of immune cells.
平滑肌的非等距动力学模型。
DOI：
10.1152/ajpcell.1997.272.3.c1025
发表时间：
1997
期刊：
The American journal of physiology.
影响因子：
--
作者：
Yu,SN;Crago,PE;Chiel,HJ
通讯作者：
Chiel,HJ
人类免疫缺陷病毒1型的包膜糖蛋白：对免疫功能的深远影响。
DOI：
10.1128/mr.60.2.386-406.1996
发表时间：
1996
期刊：
Microbiological reviews
影响因子：
--
作者：
Chirmule,N;Pahwa,S
通讯作者：
Pahwa,S
DOI：
10.1073/pnas.93.2.700
发表时间：
1996-01-23
影响因子：
11.1
作者：
Schmidtmayerova, H;Nottet, HSLM;Sherry, B
通讯作者：
Sherry, B