在先天的免疫系統(tǒng)中,，防御素是能夠清除外來微生物的重要分子,。但是在高濃度下，它們會(huì)對自身的細(xì)胞表現(xiàn)出毒性,。一直以來,，人體自身保護(hù)自己的細(xì)胞免受防御素危害的機(jī)制還不十分明了。最近,，日本札晃醫(yī)科大學(xué)Yoshio Kuroki等人發(fā)現(xiàn)hBD3（人類β防御素3）危害肺部表皮細(xì)胞的毒性會(huì)因?yàn)镾P-A（肺表面活性物質(zhì)相關(guān)蛋白A）而衰減,，因此，SP-A很可能會(huì)成為在炎癥期間保護(hù)組織的治療藥物,。相關(guān)論文發(fā)表在3月14日的美國《生化周刊》（JBC）上,。
自從發(fā)現(xiàn)在SP-A 中預(yù)培養(yǎng)的上皮細(xì)胞不會(huì)受到hBD3的細(xì)胞毒性作用后，SP-A 與hBD3的直接作用可能會(huì)讓SP-A 成為降低hBD3毒性的重要因子。與體外分析一致,，相比于對WT老鼠的作用,，對SP-A-/- 老鼠氣管內(nèi)給予hBD3 后，肺部表皮會(huì)出現(xiàn)更嚴(yán)重的組織損傷,。這些數(shù)據(jù)表明,，SP-A 保護(hù)了肺部上皮免受 hBD3造成的組織損傷。
此外,，研究發(fā)現(xiàn),，SP-A的功能性區(qū)域在于Tyr161-Lys201。目前已經(jīng)人工合成了這段區(qū)域,，暫且被稱為SP-A Y161-G200,。后續(xù)實(shí)驗(yàn)表面，它也可以抑制hBD3的細(xì)胞毒性,。所以,，SP-A Y161-G200很可能會(huì)成為一個(gè)在炎癥期間保護(hù)組織的治療藥物。（生物谷Bioon.com）
doi: 10.1074/jbc.M111.308056
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PMID:
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.
