Surfactant protein A inhibits T cell proliferation via its collagen-like tail and a 210-kDa receptor
Surfactant protein A inhibits T cell proliferation via its collagen-like tail and a 210-kDa receptor
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DOI：
10.1152/ajplung.1998.275.4.l679
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发表时间：
1998-10-01
影响因子：
4.9
通讯作者：
Fraher, LJ
中科院分区：
文献类型：
--
作者：
Borron, P;McCormack, FX;Fraher, LJ
对描述肺白细胞低反应性的可能机制的研究导致了对肺表面活性物质及其组分作为免疫抑制剂的研究。肺表面活性物质是一种磷脂-蛋白质混合物，可降低肺的表面张力，防止肺泡塌陷。这种混合物中最丰富的蛋白质是一种称为表面活性剂相关蛋白A（SP-A）的亲水性分子。以前，我们发现牛（B）SP-A可以抑制体外人T淋巴细胞增殖和白细胞介素2的产生。结果表明，不同来源的人SP-A和bSP-A以及重组大鼠SP-A均能抑制人T淋巴细胞增殖，并呈剂量依赖性。一种结构相似的胶原蛋白，Clq，没有阻止SP-A的体外抑制作用。向SP-A处理的培养物中加入大浓度的甘露聚糖也没有破坏抑制作用，这表明该作用不是由SP-A的碳水化合物识别结构域介导的。使用重组突变SP-A揭示了36个氨基酸的Arg-Gly-Asp（RGD）基序的胶原样结构域的跨度负责抑制T细胞增殖。抗SP-A受体的多克隆抗血清（SP-RS 10）完全阻断了SP-A对T细胞增殖的抑制。这些结果强调了SP-A在抑制淋巴细胞对外源性刺激的反应中的潜在作用。这些数据还进一步支持了SP-A在清除吸入病原体和保护免受附带免疫介导的损伤之间保持平衡的概念。
Investigation of possible mechanisms to describe the hyporesponsiveness of pulmonary leukocytes has led to the study of pulmonary surfactant and its constituents as immune suppressive agents. Pulmonary surfactant is a phospholipid-protein mixture that reduces surface tension in the lung and prevents collapse of the alveoli. The most abundant protein in this mixture is a hydrophilic molecule termed surfactant-associated protein A (SP-A). Previously, we showed that bovine (b) SP-A can inhibit human T lymphocyte proliferation and interleukin-2 production in vitro. Results presented in this investigation showed that different sources of human SP-A and bSP-A as well as recombinant rat SP-A inhibited human T lymphocyte proliferation in a dose-dependent manner. A structurally similar collagenous protein, Clq, did not block the in vitro inhibitory action of SP-A. The addition of large concentrations of mannan to SP-A-treated cultures also did not disrupt inhibition, suggesting that the effect is not mediated by the carbohydrate recognition domain of SP-A. Use of recombinant mutant SP-As revealed that a 36-amino acid Arg-Gly-Asp (RGD) motif-containing span of the collagen-like domain was responsible for the inhibition of T cell proliferation. A polyclonal antiserum directed against an SP-A receptor (SP-RS10) completely blocked the inhibition of T cell proliferation by SP-A. These results emphasize a potential role for SP-A in dampening lymphocyte responses to exogenous stimuli. The data also provide further support for the concept that SP-A maintains a balance between the clearance of inhaled pathogens and protection against collateral immune-mediated damage.