| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Biochemical Institute, Christian-Albrechts-University Kiel and
Institute of Infection Medicine, University Hospital Schleswig-Holstein, Kiel, Germany;
Department of Biological and Environmental Sciences, Division of Biochemistry, University of Helsinki, Helsinki, Finland; and
Department of Periodontology and
¶ Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam, Universiteit van Amsterdam and Vrije Universiteit, Amsterdam, The Netherlands
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Deutsche Forschungsgemeinschaft DFG SA683/6–1.
2 W.B. and M.W. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Paul Saftig, Biochemical Institute, Christian-Albrechts-University Kiel, Olshausenstrasse 40, D-24098 Kiel, Germany. E-mail address: psaftig{at}biochem.uni-kiel.de
4 Abbreviations used in this paper: PMN, polymorphonuclear leukocyte; LAMP, lysosomal-associated membrane protein; CEJ, cemento-enamel junction.
This article has been cited by other articles:
|
|
 |
|
  S.L. Gaffen and G. Hajishengallis A New Inflammatory Cytokine on the Block: Re-thinking Periodontal Disease and the Th1/Th2 Paradigm in the Context of Th17 Cells and IL-17 J. Dent. Res., September 1, 2008; 87(9): 817 - 828. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Yu, M. J. Ruddy, H. R. Conti, K. Boonanantanasarn, and S. L. Gaffen The Interleukin-17 Receptor Plays a Gender-Dependent Role in Host Protection against Porphyromonas gingivalis-Induced Periodontal Bone Loss Infect. Immun., September 1, 2008; 76(9): 4206 - 4213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sasaki, N. Suzuki, R. Kent Jr., N. Kawashima, J. Takeda, and P. Stashenko T Cell Response Mediated by Myeloid Cell-Derived IL-12 Is Responsible for Porphyromonas gingivalis-Induced Periodontitis in IL-10-Deficient Mice J. Immunol., May 1, 2008; 180(9): 6193 - 6198. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
