Lipoxin A4 regulates bronchial epithelial cell responses to acid injury

Caroline Bonnans, Koichi Fukunaga, Marilyn A. Levy, Bruce D. Levy

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Aspiration of gastric acid commonly injures airway epithelium and, if severe, can lead to respiratory failure from acute respiratory distress syndrome. Recently, we identified cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) and lipoxin A4 (LXA4) as pivotal mediators in vivo for resolution of acid-initiated acute lung injury. To examine protective mechanisms for these mediators in the airway, we developed an in vitro model of acid injury by transiently exposing well-differentiated normal human bronchial epithelial cells to hydrochloric acid. Transmission electron microscopy revealed selective injury to superficial epithelial cells with disruption of cell attachments and cell shedding. The morphological features of injury were substantially resolved within 6 hours. Acid triggered and early marked increases in COX-2 expression and PGE2 production, and acid-induced PGE2 significantly increased epithelial LXA 4 receptor (ALX) expression. LXA4 is generated in vivo during acute lung injury, and we observed that nanomolar quantities increased basal epithelial cell proliferation and potently blocked acid-triggered interleukin-6 release and neutrophil transmigration across well-differentiated normal human bronchial epithelial cells. Expression of recombinant human ALX in A549 airway epithelial cells uncovered ALX-dependent inhibition of cytokine release by EXA4. Together, these findings indicate that injured bronchial epithelial cells up-regulate ALX in a COX-2-dependent manner to promote LXA4-mediated resolution of airway inflammation.

Original languageEnglish
Pages (from-to)1064-1072
Number of pages9
JournalAmerican Journal of Pathology
Volume168
Issue number4
DOIs
Publication statusPublished - 2006 Apr
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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