Pulmonary surfactant proteins a and D directly suppress CD3+/CD4+ cell function:: Evidence for two shared mechanisms1
Pulmonary surfactant proteins a and D directly suppress CD3+/CD4+ cell function:: Evidence for two shared mechanisms1
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DOI：
10.4049/jimmunol.169.10.5844
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发表时间：
2002-11-15
影响因子：
4.4
通讯作者：
Wright, JR
中科院分区：
文献类型：
--
作者：
Borron, PJ;Mostaghel, EA;Wright, JR
肺表面活性物质是一种脂蛋白复合物，可降低肺气液界面的表面张力，参与肺宿主防御。表面活性剂蛋白（SP）SP-A和SP-D调节多种免疫细胞功能，包括细胞因子和自由基的产生。先前的研究表明，SP-A和SP-D在辅助细胞存在的情况下抑制淋巴细胞增殖。本研究的目的是确定SP-A和SP-D是否直接抑制Th细胞功能。两种蛋白均以非IL-2依赖的方式抑制PMA和离子霉素诱导的CD 3（+）/CD 4（+）淋巴细胞增殖。这两种蛋白质都减少了进入细胞周期S期和有丝分裂期的细胞数量。当用PMA和离子霉素处理Th细胞时，SP-A和SP-D均不改变细胞活力、凋亡或IL-2、IL-4或IFN-γ的分泌。然而，这两种蛋白质减弱离子霉素诱导的胞浆游离钙（[Ca 2 + ]（i）），但不是毒胡萝卜素诱导的[Ca 2 +]（i）的变化。总之，SP-A和SP-D对T细胞增殖的抑制通过两种机制发生，即用辅助细胞依赖性T细胞有丝分裂原和特异性Ag观察到的IL-2依赖性机制，以及可能涉及[Ca 2 +]衰减的IL-2非依赖性抑制机制（i）。
Pulmonary surfactant is a lipoprotein complex that lowers surface tension at the air-liquid interface of the lung and participates in pulmonary host defense. Surfactant proteins (SP), SP-A and SP-D, modulate a variety of immune cell functions, including the production of cytokines and free radicals. Previous, studies showed that SP-A and SP-D inhibit lymphocyte proliferation in the presence of accessory cells. The goal of this study was to determine whether SP-A and SP-D directly suppress Th cell function. Both proteins inhibited CD3(+)/CD4(+) lymphocyte proliferation induced by PMA and ionomycin in an IL-2-independent manner. Both proteins decreased the number of cells entering the S and mitotic phases of the cell cycle. Neither SP-A nor SP-D altered cell viability, apoptosis, or secretion of IL-2, IL-4, or IFN-gamma when Th cells were treated with PMA and ionomycin. However, both proteins attenuated ionomycin-induced cytosolic free calcium ([Ca2+ ](i)), but not thapsigargin-induced changes in [Ca2+](i). In summary, inhibition of T cell proliferation by SP-A and SP-D occurs via two mechanisms, an IL-2-dependent mechanism observed with accessory cell-dependent T cell mitogens and specific Ag, as well as an IL-2-independent mechanism of suppression that potentially involves attenuation of [Ca2+](i).