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Aggregatibacter actinomycetemcomitans induces detachment and death of human gingival epithelial cells and fibroblasts via elastase release following leukotoxin‐dependent neutrophil lysis
Author(s) -
Hiyoshi Takumi,
Domon Hisanori,
Maekawa Tomoki,
Nagai Kosuke,
Tamura Hikaru,
Takahashi Naoki,
Yonezawa Daisuke,
Miyoshi Tomohiro,
Yoshida Akihiro,
Tabeta Koichi,
Terao Yutaka
Publication year - 2019
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/1348-0421.12672
Subject(s) - aggregatibacter actinomycetemcomitans , elastase , periodontitis , neutrophil elastase , cytotoxicity , biology , saliva , microbiology and biotechnology , gingival and periodontal pocket , aggressive periodontitis , programmed cell death , immunology , collagenase , neutrophile , apoptosis , porphyromonas gingivalis , in vitro , inflammation , medicine , biochemistry , dentistry , enzyme
Aggregatibacter actinomycetemcomitans is considered to be associated with periodontitis. Leukotoxin (LtxA), which destroys leukocytes in humans, is one of this bacterium's major virulence factors. Amounts of neutrophil elastase (NE), which is normally localized in the cytoplasm of neutrophils, are reportedly increased in the saliva of patients with periodontitis. However, the mechanism by which NE is released from human neutrophils and the role of NE in periodontitis is unclear. In the present study, it was hypothesized that LtxA induces NE release from human neutrophils, which subsequently causes the breakdown of periodontal tissues. LtxA‐treatment did not induce significant cytotoxicity against human gingival epithelial cells (HGECs) or human gingival fibroblasts (HGFs). However, it did induce significant cytotoxicity against human neutrophils, leading to NE release. Furthermore, NE and the supernatant from LtxA‐treated human neutrophils induced detachment and death of HGECs and HGFs, these effects being inhibited by administration of an NE inhibitor, sivelestat. The present results suggest that LtxA mediates human neutrophil lysis and induces the subsequent release of NE, which eventually results in detachment and death of HGECs and HGFs. Thus, LtxA‐induced release of NE could cause breakdown of periodontal tissue and thereby exacerbate periodontitis.