Xia M, Gaufo G O, Wang Q, Sreedharan S P, Goetzl E J
Department of Medicine, University of California, San Francisco, CA 94143, USA.
J Immunol. 1996 Aug 1;157(3):1132-8.
The major immunoregulatory effects of vasoactive intestinal peptide (VIP) are mediated by structurally distinct types I (VIPR1) and II (VIPR2) G protein-associated receptors on some T cells, B cells, and macrophages. Identification of the separate immunologic activities of each type of VIPR has been complicated by the usual expression of only VIPR2 or of VIPR1 and VIPR2 together by most human T cells obtainable in sufficient number for functional analyses. The results of reverse-transcription PCR, Western blot, and [125I]VIP-binding studies have established that HuT 78 cultured human lymphoma T cells bear a mean of 75,000 VIPR1s per cell with a mean Kd of 3.3 nM, which transduce mean maximal increases in intracellular concentration of cAMP of 2.1-fold (ED50 = 72 nM), but no VIPR2s. HuT 78 T cells, in contrast to T cells that express VIPR2, did not respond to VIP by chemotaxis through micropore filters without or with a top layer of basement membrane-like Matrigel. Matrix metalloproteinase (MMP)-dependent in situ cleavage of [3H]type IV human collagen in the layer of Matrigel by HuT 78 T cells also was not stimulated by VIP. In contrast, IL-4 and TNF-alpha both stimulated HuT 78 T cell chemotaxis and in situ MMP activity at respective optimal concentrations ranging from 3 x 10(-10) M to 3 x 10(-9) M and 10(-10) M to 3 x 10(-10) M. VIP inhibited significantly HuT 78 T cell chemotaxis through Matrigel in response to both IL-4 and TNF-alpha, as a result of suppression of both chemotactic mobility, assessed by migration through micropore filters without Matrigel, and in situ MMP activity. The transduction of opposite effects of VIP on T cell migration through a model basement membrane by VIPR1 and VIPR2 suggests that the net chemotactic response of most T cells to VIP is determined by the VIPR2/VIPR1 ratio and that the predominant expression of VIPR1 would stabilize T cell populations in lymphoid follicles and tissue infiltrates.
血管活性肠肽（VIP）的主要免疫调节作用是由一些T细胞、B细胞和巨噬细胞上结构不同的I型（VIPR1）和II型（VIPR2）G蛋白偶联受体介导的。由于大多数可获得足够数量用于功能分析的人T细胞通常仅表达VIPR2或同时表达VIPR1和VIPR2，因此鉴定每种类型VIPR的单独免疫活性变得复杂。逆转录PCR、蛋白质印迹和[125I]VIP结合研究结果表明，培养的HuT 78人淋巴瘤T细胞平均每个细胞有75,000个VIPR1，平均解离常数（Kd）为3.3 nM，可使细胞内cAMP浓度平均最大增加2.1倍（半数有效浓度[ED50]=72 nM），但不表达VIPR2。与表达VIPR2的T细胞不同，HuT 78 T细胞在无或有一层基底膜样基质胶的微孔滤器中对VIP没有趋化反应。HuT 78 T细胞对基质胶层中[3H]IV型人胶原的基质金属蛋白酶（MMP）依赖性原位切割也不受VIP刺激。相反，白细胞介素-4（IL-4）和肿瘤坏死因子-α（TNF-α）在各自最佳浓度范围（3×10^(-10) M至3×10^(-9) M和10^(-10) M至3×10^(-10) M）时均刺激HuT 78 T细胞趋化和原位MMP活性。由于抑制了趋化迁移（通过无基质胶的微孔滤器迁移评估）和原位MMP活性，VIP显著抑制HuT 78 T细胞对IL-4和TNF-α的通过基质胶的趋化反应。VIPR1和VIPR2对VIP通过模型基底膜对T细胞迁移产生相反作用的转导表明，大多数T细胞对VIP的净趋化反应由VIPR2/VIPR1比率决定，并且VIPR1的主要表达将稳定淋巴滤泡和组织浸润中的T细胞群体。
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