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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\u2010treatment 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\u2010treated 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\u2010induced release of NE could cause breakdown of periodontal tissue and thereby exacerbate periodontitis.<\/jats:p>","DOI":"10.1111\/1348-0421.12672","type":"journal-article","created":{"date-parts":[[2019,2,28]],"date-time":"2019-02-28T17:19:37Z","timestamp":1551374377000},"page":"100-110","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["<i>Aggregatibacter actinomycetemcomitans<\/i> induces detachment and death of human gingival epithelial cells and fibroblasts via elastase release following leukotoxin\u2010dependent neutrophil lysis"],"prefix":"10.1111","volume":"63","author":[{"given":"Takumi","family":"Hiyoshi","sequence":"first","affiliation":[{"name":"Division of Microbiology and Infectious Diseases Niigata University Graduate School of Medical and Dental Sciences Niigata Japan"},{"name":"Division of Periodontology Niigata University Graduate School of Medical and Dental Sciences Niigata 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