在先天的免疫系统中，防御素是能够清除外来微生物的重要分子。但是在高浓度下，它们会对自身的细胞表现出毒性。一直以来，人体自身保护自己的细胞免受防御素危害的机制还不十分明了。最近，日本札晃医科大学Yoshio Kuroki等人发现hBD3（人类β防御素3）危害肺部表皮细胞的毒性会因为SP-A（肺表面活性物质相关蛋白A）而衰减，因此，SP-A很可能会成为在炎症期间保护组织的治疗药物。相关论文发表在3月14日的美国《生化周刊》（JBC）上。
自从发现在SP-A 中预培养的上皮细胞不会受到hBD3的细胞毒性作用后，SP-A 与hBD3的直接作用可能会让SP-A 成为降低hBD3毒性的重要因子。与体外分析一致，相比于对WT老鼠的作用，对SP-A-/- 老鼠气管内给予hBD3 后，肺部表皮会出现更严重的组织损伤。这些数据表明，SP-A 保护了肺部上皮免受 hBD3造成的组织损伤。
此外，研究发现，SP-A的功能性区域在于Tyr161-Lys201。目前已经人工合成了这段区域，暂且被称为SP-A Y161-G200。后续实验表面，它也可以抑制hBD3的细胞毒性。所以，SP-A Y161-G200很可能会成为一个在炎症期间保护组织的治疗药物。（生物谷Bioon.com）
doi: 10.1074/jbc.M111.308056
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Pulmonary surfactant protein A protects lung epithelium from cytotoxicity of human β-defensin 3
Atsushi Saito1, Shigeru Ariki1,, Hitoshi Sohma1, Chiaki Nishitani, Kanako Inoue, Nobutaka Ebata, Motoko Takahashi, Yoshihiro Hasegawa, Koji Kuronuma, Hiroki Takahashi1 and Yoshio Kuroki
Defensins are important molecules in the innate immune system that eliminate infectious microbes. They also exhibit cytotoxicity against host cells in higher concentrations. The mechanisms by which hosts protect their own cells from cytotoxicity of defensins have been poorly understood. We found that the cytotoxicity of human β-defensin 3 (hBD3) against lung epithelial cells was dose-dependently attenuated by pulmonary surfactant protein A (SP-A), a collectin implicated in host defense and regulation of inflammatory responses in the lung.The direct interaction between SP-A and hBD3 may be an important factor in decreasing this cytotoxicity, since preincubation of epithelial cells with SP-A did not affect the cytotoxicity. Consistent with in vitro analysis, intratracheal administration of hBD3 to SP-A-/- mice resulted in more severe tissue damage compared to that in WT mice. These data indicate that SP-A protects lung epithelium from tissue injury caused by hBD3.Furthermore, we found that the functional region of SP-A lies within Tyr161-Lys201. Synthetic peptide corresponding to this region, tentatively called SP-A Y161-G200, also inhibited cytotoxicity of hBD3 in a dose-dependent manner. The SP-A Y161-G200 is a candidate as a therapeutic reagent that prevent tissue injury during inflammation.
