好酸球性副鼻腔炎の疑問

• 清水 猛史

  滋賀医科大学耳鼻咽喉科学講座

書誌事項

タイトル別名

• Role of Coagulation Factors and Eosinophils in Chronic Rhinosinusitis-associated Tissue Remodeling
• コウサンキュウセイ フクビコウエン ノ ギモン : ニカワ ヨウ ハナシル ノ ホンタイ ワ ナニ カ?コウサンキュウ ワ ナニ オ シテ イル ノ カ?
• ―ニカワ様鼻汁の本態は何か？好酸球は何をしているのか？―

抄録

Airway inflammation is associated with increased permeability and leakage of plasma coagulation factors, leading to activation of the coagulation system. We reported the detection of significant concentrations of thrombin and of the thrombin-antithrombin III complex in the nasal secretions of patients with chronic rhinosinusitis. We revealed that the thrombin and PAR-1 agonist peptide stimulated the secretion of PDGF, VEGF and MUC5AC mucin from cultured airway epithelial cells. We also found higher expressions of PDGF, VEGF and their receptors in nasal polyps, suggesting that thrombin-induced PDGF and VEGF may be involved in the formation of nasal polyps. Intranasal instillation of thrombin induced goblet cell metaplasia and mucus production in the rat nasal epithelium in vivo. These results indicate that sinonasal inflammation may be associated with activation of the coagulation system and that thrombin may play a crucial role in tissue remodeling, such as goblet cell metaplasia and formation of nasal polyps. Activated protein C (APC) and heparin are anticoagulant drugs used in clinical practice, and both possess anti-inflammatory activities. We also demonstrated that nasal administration of the anticoagulant drug APC or heparin may represent a new therapeutic strategy for the treatment of chronic rhinosinusitis.<br> To elucidate the roles of eosinophils in the pathogenesis of eosinophilic rhinosinusitis, eosinophil-epithelial interactions were examined by co-culture of the airway epithelial cell line NCI-H292 with the eosinophilic cell line EoL-1. Eosinophil-epithelial interactions significantly stimulated the secretion of PDGF, VEGF, MUC5AC, IL-8 and TGF-β from the epithelial cells. The EGFR tyrosine kinase inhibitor AG1478 inhibited the co-culture-induced secretion of MUC5AC, PDGF, VEGF and IL-8. Neutralizing antibodies directed against TGF-α or amphiregulin and the pan-metalloprotease inhibitor GM6001 inhibited the secretion of MUC5AC from the co-cultured epithelial cells. These results indicate that eosinophil-epithelial interactions stimulate tissue remodeling induced by PDGF, VEGF and MUC5AC mucin, probably mediated by EGFR transactivation via amphiregulin and TGF-α released from the epithelial cells.<br>

収録刊行物

• 耳鼻咽喉科臨床

  耳鼻咽喉科臨床 105 (9), 803-812, 2012

  耳鼻咽喉科臨床学会

キーワード

• eosinophil
• chronic rhinosinusitis
• thrombin
• mucin
• heparin

詳細情報

• CRID: 1390001204272422272
• NII論文ID: 10031012193
• NII論文ID: 130002141246
• NII書誌ID: AN00107089
• DOI: 10.5631/jibirin.105.803
• ISSN: 18844545
• ISSN: 00326313
• NDL書誌ID: 023963588
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I023963588
• Web Site: https://search.jamas.or.jp/link/ui/2013017987
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可