Impaired phagosomal maturation in neutrophils leads to periodontitis in lysosomal-associated membrane protein-2 knockout mice

Research output: Contribution to journalResearch articleContributedpeer-review


  • Wouter Beertsen - , University of Amsterdam (Author)
  • Marion Willenborg - , Kiel University (Author)
  • Vincent Everts - , University of Amsterdam (Author)
  • Angelika Zirogianni - , University of Amsterdam (Author)
  • Rainer Podschun - , Kiel University (Author)
  • Bernd Schröder - , Institute of Physiological Chemistry, Kiel University (Author)
  • Eeva Liisa Eskelinen - , University of Helsinki (Author)
  • Paul Saftig - , Kiel University (Author)


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.


Original languageEnglish
Pages (from-to)475-482
Number of pages8
JournalJournal of Immunology
Issue number1
Publication statusPublished - 1 Jan 2008

External IDs

PubMed 18097049


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