兩種不同的化學(xué)物質(zhì),，一種與阿爾茨海默氏癥有關(guān),，一種與嚴(yán)重的肺部疾病有關(guān)，卻以相同的方法引發(fā)了炎癥,，這是研究人員在日前在線出版的《自然—免疫學(xué)》（Nature Immunology）期刊上的論文中報(bào)告的,。新發(fā)現(xiàn)為這類疾病的治療提供了新靶標(biāo)。
二氧化硅能導(dǎo)致硅肺病,。從細(xì)菌毒素到二氧化硅等多種晶體,，均能通過激發(fā)細(xì)胞中一種名為炎癥蛋白的蛋白質(zhì)復(fù)合體引發(fā)炎癥。Eicke Latz和Douglas Golenbock領(lǐng)導(dǎo)的一個研究小組顯示,，因?yàn)楸患?xì)胞吸收而產(chǎn)生炎癥,，二氧化硅晶體和β-淀粉蛋白質(zhì)的形成與阿爾茨海默氏癥有關(guān)。這一過程包括組織蛋白酶B蛋白質(zhì)從溶酶體細(xì)胞腔中的滲出和對細(xì)胞碎片的破壞,。組織蛋白酶B的滲出激發(fā)了與硅肺病和阿爾茨海默氏癥相關(guān)的失控性免疫反應(yīng),。
這種信號的級聯(lián)反應(yīng)很可能也與痛風(fēng)等炎癥性疾病有很大關(guān)系，因此,，新研究也為這類疾病的治療提供了一種通用靶標(biāo),。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Immunology，doi:10.1038/ni.1631,，Veit Hornung,，Eicke Latz
Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization
Veit Hornung1,5, Franz Bauernfeind2,5, Annett Halle1, Eivind O Samstad1,3, Hajime Kono4, Kenneth L Rock4, Katherine A Fitzgerald1 & Eicke Latz1,3
Abstract
Inhalation of silica crystals causes inflammation in the alveolar space. Prolonged exposure to silica can lead to the development of silicosis, an irreversible, fibrotic pulmonary disease. The mechanisms by which silica and other crystals activate immune cells are not well understood. Here we demonstrate that silica and aluminum salt crystals activated inflammasomes formed by the cytoplasmic receptor NALP3. NALP3 activation required phagocytosis of crystals, and this uptake subsequently led to lysosomal damage and rupture. 'Sterile' lysosomal damage (without crystals) also induced NALP3 activation, and inhibition of either phagosomal acidification or cathepsin B activity impaired NALP3 activation. Our results indicate that the NALP3 inflammasome senses lysosomal damage as an endogenous 'danger' signal.
1 Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
2 Division of Clinical Pharmacology, Department of Internal Medicine, Ludwig-Maximilians University of Munich 80336, Germany.
3 Institute of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, N-7489 Trondheim, Norway.
4 Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
5 These authors contributed equally to this work.
