6月21日,，Science在線報道了人α-防御素（HD）6在腸道免疫中的重要作用,。
防御素是一種抗菌肽,，它廣泛地發(fā)揮促進先天免疫系統(tǒng)的功能,，包括保護粘膜組織,。人α-防御素（HD）6在小腸分泌性潘氏細胞高表達,。然而，在對比其他防御素,，它缺乏明顯的殺菌活性,。
盡管如此，本研究發(fā)現(xiàn),，在體外和體內(nèi)實驗中,，HD6均可抵抗腸道細菌病原體的侵襲。隨機地與細菌表面的蛋白質(zhì)結合后,，HD6經(jīng)過有序自組裝形成包圍和糾纏細菌的小纖維和納米網(wǎng),。這種自我組裝機制發(fā)生在體內(nèi),，需要組氨酸-27，并與X射線晶體學數(shù)據(jù)是一致的,。
這些發(fā)現(xiàn)說明,，在保護小腸免受多種腸道致病菌侵害過程中，HD6發(fā)揮關鍵作用,，并可以解釋整個人類進化中HD6的保守性,。（生物谷bioon.com）
doi:10.1016/j.cell.2011.10.017
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Human α-Defensin 6 Promotes Mucosal Innate Immunity Through Self-Assembled Peptide Nanonets
Hiutung Chu1, Marzena Pazgier2, Grace Jung3, Sean-Paul Nuccio1, Patricia A. Castillo1, Maarten F. de Jong1, Maria G. Winter1, Sebastian E. Winter1, Jan Wehkamp1,*, Bo Shen4, Nita H. Salzman5, Mark A. Underwood6, Renee M. Tsolis1, Glenn M. Young7, Wuyuan Lu2,?, Robert I. Lehrer3,?, Andreas J. B?umler1,?, Charles L. Bevins
Defensins are antimicrobial peptides that contribute broadly to innate immunity, including protection of mucosal tissues. Human α-defensin (HD) 6 is highly expressed by secretory Paneth cells of the small intestine. However, in contrast to the other defensins, it lacks appreciable bactericidal activity. Nevertheless, we report here that HD6 affords protection against invasion by enteric bacterial pathogens in vitro and in vivo. After stochastic binding to bacterial surface proteins, HD6 undergoes ordered self-assembly to form fibrils and nanonets that surround and entangle bacteria. This self-assembly mechanism occurs in vivo, requires histidine-27, and is consistent with x-ray crystallography data. These findings support a key role for HD6 in protecting the small intestine against invasion by diverse enteric pathogens and may explain the conservation of HD6 throughout Hominidae evolution.
