Qi Jian Cheng, Stevens Richard L, Wadley Robert, Collins Andrew, Cooley Margaret, Naif Hassan M, Nasr Najla, Cunningham Anthony, Katsoulotos Gregory, Wanigasek Yewlan, Roufogalis Basil, Krilis Steven A
Department of Medicine, University of New South Wales, Australia.
J Immunol. 2002 Apr 15;168(8):4127-34. doi: 10.4049/jimmunol.168.8.4127.
AIDS patients often contain HIV-1-infected mast cells (MCs)/basophils in their peripheral blood, and in vivo-differentiated MCs/basophils have been isolated from the blood of asthma patients that are HIV-1 susceptible ex vivo due to their surface expression of CD4 and varied chemokine receptors. Because IL-16 is a ligand for CD4 and/or an undefined CD4-associated protein, the ability of this multifunctional cytokine to regulate the development of human MCs/basophils from nongranulated progenitors residing in cord or peripheral blood was evaluated. After 3 wk of culture in the presence of c-kit ligand, IL-16 induced the progenitors residing in the blood of normal individuals to increase their expression of chymase and tryptase about 20-fold. As assessed immunohistochemically, >80% of these tryptase(+) and/or chymase(+) cells expressed CD4. The resulting cells responded to IL-16 in an in vitro chemotaxis assay, and this biologic response could be blocked by anti-IL-16 and anti-CD4 Abs as well as by a competitive peptide inhibitor corresponding to a sequence in the C-terminal domain of IL-16. The additional finding that IL-16 induces calcium mobilization in the HMC-1 cell line indicates that IL-16 acts directly on MCs and their committed progenitors. IL-16-treated MCs/basophils also are less susceptible to infection by an M/R5-tropic strain of HIV-1. Thus, IL-16 regulates MCs/basophils at a number of levels, including their vulnerability to retroviral infection.
艾滋病患者外周血中常含有感染HIV-1的肥大细胞（MCs）/嗜碱性粒细胞，并且已从哮喘患者血液中分离出体内分化的MCs/嗜碱性粒细胞，这些细胞由于其表面表达CD4和多种趋化因子受体，在体外对HIV-1易感。由于白细胞介素-16（IL-16）是CD4的配体和/或一种未明确的CD4相关蛋白，因此评估了这种多功能细胞因子对源自脐带血或外周血中无颗粒祖细胞的人MCs/嗜碱性粒细胞发育的调节能力。在存在c-kit配体的情况下培养3周后，IL-16诱导正常个体血液中的祖细胞将其糜蛋白酶和组织蛋白酶的表达增加约20倍。通过免疫组织化学评估，这些组织蛋白酶（+）和/或糜蛋白酶（+）细胞中>80%表达CD4。所得细胞在体外趋化性试验中对IL-16有反应，并且这种生物学反应可被抗IL-16和抗CD4抗体以及对应于IL-16 C末端结构域序列的竞争性肽抑制剂阻断。另外的发现是IL-16在HMC-1细胞系中诱导钙动员，这表明IL-16直接作用于MCs及其定向祖细胞。经IL-16处理的MCs/嗜碱性粒细胞对HIV-1的M/R5嗜性毒株感染也较不敏感。因此，IL-16在多个水平上调节MCs/嗜碱性粒细胞，包括它们对逆转录病毒感染的易感性。
