吞噬体
炎症
牙周炎
先天免疫系统
内体
细胞生物学
液泡
生物
免疫学
切迪亚克-东综合征
内吞循环
吞噬作用
免疫系统
医学
内吞作用
细胞内
内科学
细胞
遗传学
细胞质
作者
W. Beertsen,Marion Willenborg,Vincent Everts,Angelika Zirogianni,Rainer Podschun,Bernd Schröder,Eeva‐Liisa Eskelinen,Paul Säftig
出处
期刊:Journal of Immunology
[American Association of Immunologists]
日期:2008-01-01
卷期号:180 (1): 475-482
被引量:79
标识
DOI:10.4049/jimmunol.180.1.475
摘要
Abstract Inflammatory periodontal diseases constitute one of the most common infections in humans, resulting in the destruction of the supporting structures of the dentition. Circulating neutrophils are an essential component of the human innate immune system. We observed that mice deficient for the major lysosomal-associated membrane protein-2 (LAMP-2) developed severe periodontitis early in life. This development was accompanied by a massive accumulation of bacterial plaque along the tooth surfaces, gingival inflammation, alveolar bone resorption, loss of connective tissue fiber attachment, apical migration of junctional epithelium, and pathological movement of the molars. The inflammatory lesions were dominated by polymorphonuclear leukocytes (PMNs) apparently being unable to efficiently clear bacterial pathogens. Systemic treatment of LAMP-2-deficient mice with antibiotics prevented the periodontal pathology. Isolated PMNs from LAMP-2-deficient mice showed an accumulation of autophagic vacuoles and a reduced bacterial killing capacity. Oxidative burst response was not altered in these cells. Latex bead and bacterial feeding experiments showed a reduced ability of the phagosomes to acquire an acidic pH and late endocytic markers, suggesting an impaired fusion of late endosomes-lysosomes with phagosomes. This study underlines the importance of LAMP-2 for the maturation of phagosomes in PMNs. It also underscores the requirement of lysosomal fusion events to provide sufficient antimicrobial activity in PMNs, which is needed to prevent periodontal disease.
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