N36, a synthetic N-terminal heptad repeat domain of the HIV-1 envelope protein gp41, is an activator of human phagocytes
N36, a synthetic N-terminal heptad repeat domain of the HIV-1 envelope protein gp41, is an activator of human phagocytes
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DOI：
10.1006/clim.2000.4896
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发表时间：
2000-09-01
影响因子：
8.6
通讯作者：
Wang, JM
中科院分区：
文献类型：
--
作者：
Le, YY;Jiang, S;Wang, JM
人类免疫缺陷病毒1型（HIV-1）包膜蛋白gp 41介导病毒与人类宿主细胞的融合。在本研究中，我们证明了N36，一种衍生自gp 41的N-末端的合成肽，诱导人单核细胞和中性粒细胞的定向迁移和钙动员。N36对吞噬细胞的活性是百日咳毒素敏感的，这表明涉及一种Gi偶联的七跨膜受体，由于高浓度的细菌趋化肽fMet-Leu-Phe（fMLF）部分脱敏了吞噬细胞中N36的钙动员活性，我们推测N36可能使用低亲和力的fMLF受体。通过使用稳定表达fMLF受体FPR或FPRL 1的细胞，我们证明N36使用FPRL 1作为功能性受体。我们的研究结果表明，HIV-1 gp 41可能含有一个片段，通过FPRL 1激活先天性宿主免疫细胞。由于单核细胞中FPRL 1的激活已被证明是异源脱敏趋化因子受体，减少在艾滋病患者中看到的吞噬细胞对化学引诱剂的反应可能归因于，至少部分，异源脱敏。(C)北京大学出版社.
Human immunodeficiency virus type 1 (HIV-1) envelope protein gp41 mediates viral fusion with human host cells. In this study we show that N36, a synthetic peptide derived from the N-terminus of gp41, induced directional migration and calcium mobilization in human monocytes and neutrophils, The activity of N36 on phagocytes was pertussis toxin sensitive, suggesting involvement of a Gi-coupled seven-transmembrane receptor(s), Since high concentrations of the bacterial chemotactic peptide fMet-Leu-Phe (fMLF) partially desensitized the calcium mobilizing activity of N36 in phagocytes, we postulated that N36 might use a low-affinity fMLF receptor. By using cells stably expressing fMLF receptor FPR or FPRL1, we demonstrate that N36 uses FPRL1 as a functional receptor. Our results suggest that HIV-1 gp41 may contain a fragment(s) that activates the innate host immune cells through FPRL1, Since the activation of FPRL1 in monocytes has been shown to heterologously desensitize chemokine receptors, the reduced phagocyte response to chemoattractants seen in AIDS patients may be attributed, at least in part, to heterologous desensitization. (C) 2000 Academic Press.