TGF-β1 in SP-A preparations influence immune suppressive properties of SP-A on human CD4+ T lymphocytes
TGF-β1 in SP-A preparations influence immune suppressive properties of SP-A on human CD4+ T lymphocytes
复制标题
DOI：
10.1152/ajplung.00401.2005
复制
发表时间：
2006-10-01
影响因子：
4.9
通讯作者：
Schmidt-Weber, Carsten
中科院分区：
文献类型：
--
作者：
Kunzmann, Steffen;Wright, Jo Rae;Schmidt-Weber, Carsten
SP-A制剂中的TGF-β 1影响SP-A对人CD 4（+）T淋巴细胞的免疫抑制特性。美国生理学杂志肺细胞分子生理学291：L747-L756，2006年。首次发表于2006年4月28日; doi：10.1152/ajplung.00401.2005。表面活性剂蛋白A（SP-A）和转化生长因子-β（1）（TGF-β 1）已被证明可调节不同免疫细胞的功能，并特异性地抑制T淋巴细胞增殖。本研究的目的是阐明TGF-β 1激活的Smad信号通路是否也在SP-A介导的抑制CD 4（+）T淋巴细胞活化中发挥作用。在中国仓鼠卵巢细胞中表达的重组人SP-A1 [rSP-A1 m（哺乳动物）]，而不是重组杆状病毒衍生的rSP-A1（hyp）（羟脯氨酸缺乏），抑制T淋巴细胞增殖和IL-2 mRNA表达。为了测试SP-A是否诱导Smad信号传导，将Smad 3/4特异性报告基因转染原代人CD 4（+）T淋巴细胞。只有rSP-A1 m，而不是rSP-A1（羟脯氨酸），诱导Smad特异性报告基因，Smad 2磷酸化，Smad 7 mRNA表达。rSP-A1 m的作用是通过TGF-β RII介导的，并且可以被抗TGF-β 1中和抗体和sTGF-β RII拮抗。Western blot和ELISA分析显示rSP-A1 m含有TGF-β 1，而rSP-A1（hyp）不含。TGF-β 1对rSP-A1 m和rSP-A1（hyp）抑制CD 4（+）T淋巴细胞增殖和激活Smad信号通路的作用存在差异。酸化后，从肺泡蛋白沉积症患者中获得的天然SP-A也诱导人CD 4（+）T淋巴细胞中的Smad信号传导，导致T淋巴细胞增殖抑制增加，从而表明天然SP-A样品中存在无活性的潜伏性TGF-β 1。SP-A和潜在TGF-β 1之间的关联提供了一种可能的新机制来调节TGF-β 1介导的肺部炎症和纤维化反应，但也可能导致对SP-A免疫调节功能的误解。监测SP-A制剂中可能存在的TGF-β 1至关重要。
TGF-beta 1 in SP-A preparations influence immune suppressive properties of SP-A on human CD4(+) T lymphocytes. Am J Physiol Lung Cell Mol Physiol 291: L747-L756, 2006. First published April 28, 2006; doi: 10.1152/ajplung.00401.2005.-Surfactant protein A (SP-A) and transforming growth factor-beta(1) (TGF-beta 1) have been shown to modulate the functions of different immune cells and specifically to inhibit T lymphocyte proliferation. The aim of the present study was to elucidate whether the Smad signaling pathway, which is activated by TGF-beta 1, also plays a role in SP-A-mediated inhibition of CD4(+) T lymphocyte activation. Recombinant human SP-A1 expressed in Chinese hamster ovary cells [rSP-A1m ( mammalian)], but not recombinant Baculovirus-derived rSP-A1(hyp) (hydroxyprolinedeficient), suppressed T lymphocyte proliferation and IL-2 mRNA expression. To test whether SP-A induced Smad signaling, a Smad3/4-specific reporter gene was transfected in primary human CD4(+) T lymphocytes. Only rSP-A1m, but not rSP-A1(hyp), induced Smad-specific reporter genes, Smad2 phosphorylation, and Smad7 mRNA expression. The effect of rSP-A1m was mediated through the TGF-beta RII and could be antagonized by anti-TGF-beta 1 neutralizing antibodies and sTGF-beta RII. Western blot and ELISA analysis revealed that rSP-A1m, but not rSP-A1(hyp), contained TGF-beta 1. TGF-beta 1 was responsible for the differences in inhibition of CD4(+) T lymphocyte proliferation and activation of the Smad signaling pathway between rSP-A1m and rSP-A1(hyp). After acidification, native SP-A, obtained from patients with alveolar proteinosis, also induced Smad signaling in human CD4(+) T lymphocytes leading to an increased inhibition of T lymphocyte proliferation, thus indicating the presence of inactive, latent TGF-beta 1 in native SP-A samples. Association between SP-A and latent TGF-beta 1 provides a possible novel mechanism to regulate TGF-beta 1-mediated inflammation and fibrosis reactions in the lung but also leads to possible misinterpretation of immune-modulator functions of SP-A. Monitoring of SP-A preparations for possible TGF-beta 1 is essential.