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　　急性呼吸道感染造成每年4百萬以上的死亡，中性粒細(xì)胞在肺部感染的固有免疫應(yīng)答中發(fā)揮重要作用。中性粒細(xì)胞通過模式識別和分泌抗菌物質(zhì)識別和消滅感染部位的病原體。除了消滅感染病原體，中性粒細(xì)胞也能驅(qū)動炎癥反應(yīng)，從而導(dǎo)致肺功能損傷甚至嚴(yán)重的并發(fā)癥。

　　有研究表明中性粒細(xì)胞炎性蛋白——髓系細(xì)胞觸發(fā)受體1（TREM-1，triggering receptor expressed on myeloid cells）能擴(kuò)大炎癥反應(yīng)，因此有人推測敲除TREM-1后能減少炎癥反應(yīng)，提高感染存活率。然而在研究過程中，研究人員卻發(fā)現(xiàn)了相反的結(jié)果，敲除TREM-1顯著增加綠膿桿菌感染的小鼠死亡率，愛荷華大學(xué)茱莉亞-泰特的研究團(tuán)隊(duì)在12月17日的《臨床研究雜志》發(fā)表了相關(guān)結(jié)果。

　　中性粒細(xì)胞敲除TREM-1/3不影響細(xì)胞的殺菌活性，吞噬能力和趨化作用，然而TREM-1/3敲除小鼠肺部免疫組化顯示遷移到氣道的中性粒細(xì)胞顯著減少。深入研究表明雖然敲除TREM-1/3的中性粒細(xì)胞能穿過單層內(nèi)皮細(xì)胞，但卻不能穿過氣道上皮細(xì)胞，因此不能有效地遷移到感染部位。

　　研究指出炎性蛋白TREM-1在中性粒細(xì)胞遷移中產(chǎn)生的作用出乎意料，針對TREM-1為靶點(diǎn)的治療可能產(chǎn)生非預(yù)期的效果。此外，對TREM-1/3上皮遷移的進(jìn)一步研究可能幫助找到調(diào)節(jié)中性粒細(xì)胞浸潤的治療靶點(diǎn)，通過控制遷移過程而不是經(jīng)典的細(xì)胞因子信號來控制局部炎癥反應(yīng)。

　　Transepithelial migration of neutrophils into the lung requires TREM-1.

　　Klesney-Tait J, Keck K, Li X, Gilfillan S, Otero K, Baruah S, Meyerholz DK, Varga SM, Knudson CJ, Moninger TO, Moreland J, Zabner J, Colonna M.

　　J Clin Invest. 2013 Jan 2;123(1):138-49. doi: 10.1172/JCI64181. Epub 2012 Dec 17.

　　Abstract

　　Acute respiratory infections are responsible for more than 4 million deaths each year. Neutrophils play an essential role in the innate immune response to lung infection. These cells have an armamentarium of pattern recognition molecules and antimicrobial agents that identify and eliminate pathogens. In the setting of infection, neutrophil triggering receptor expressed on myeloid cells 1 (TREM-1) amplifies inflammatory signaling. Here we demonstrate for the first time that TREM-1 also plays an important role in transepithelial migration of neutrophils into the airspace. We developed a TREM-1/3-deficient mouse model of pneumonia and found that absence of TREM-1/3 markedly increased mortality following Pseudomonas aeruginosa challenge. Unexpectedly, TREM-1/3 deficiency resulted in increased local and systemic cytokine production. TREM-1/3-deficient neutrophils demonstrated intact bacterial killing, phagocytosis, and chemotaxis; however, histologic examination of TREM-1/3-deficient lungs revealed decreased neutrophil infiltration of the airways. TREM-1/3-deficient neutrophils effectively migrated across primary endothelial cell monolayers but failed to migrate across primary airway epithelia grown at the air-liquid interface. These data define a new function for TREM-1 in neutrophil migration across airway epithelial cells and suggest that it amplifies inflammation through targeted neutrophil migration into the lung.