两种不同的化学物质，一种与阿尔茨海默氏症有关，一种与严重的肺部疾病有关，却以相同的方法引发了炎症，这是研究人员在日前在线出版的《自然—免疫学》（Nature Immunology）期刊上的论文中报告的。新发现为这类疾病的治疗提供了新靶标。
二氧化硅能导致硅肺病。从细菌毒素到二氧化硅等多种晶体，均能通过激发细胞中一种名为炎症蛋白的蛋白质复合体引发炎症。Eicke Latz和Douglas Golenbock领导的一个研究小组显示，因为被细胞吸收而产生炎症，二氧化硅晶体和β-淀粉蛋白质的形成与阿尔茨海默氏症有关。这一过程包括组织蛋白酶B蛋白质从溶酶体细胞腔中的渗出和对细胞碎片的破坏。组织蛋白酶B的渗出激发了与硅肺病和阿尔茨海默氏症相关的失控性免疫反应。
这种信号的级联反应很可能也与痛风等炎症性疾病有很大关系，因此，新研究也为这类疾病的治疗提供了一种通用靶标。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
