Lipid mediator-induced expression of bactericidal/permeability-increasing protein (BPI) in human mucosal epithelia

Geraldine Canny, Ofer Levy, Glenn T. Furuta, Sailaja Narravula-Alipati, Richard B. Sisson, Charles N. Serhan, Sean P. Colgan

Research output: Contribution to journalArticlepeer-review

239 Citations (Scopus)

Abstract

Epithelial cells which line mucosal surfaces are the first line of defense against bacterial invasion and infection. Recent studies have also indicated that epithelial cells contribute significantly to the orchestration of ongoing inflammatory processes. Here, we demonstrate that human epithelial cells express bactericidal/permeability-increasing protein (BPI), an antibacterial and endotoxin-neutralizing molecule previously associated with neutrophils. Moreover, we demonstrate that such BPI expression is transcriptionally regulated by analogs of endogenously occurring anti-inflammatory eicosanoids (aspirin-triggered lipoxins, ATLa). Initial studies to verify microarray analysis revealed that epithelial cells of wide origin (oral, pulmonary, and gastrointestinal mucosa) express BPI and each is similarly regulated by aspirin-triggered lipoxins. Studies aimed at localization of BPI revealed that such expression occurs on the cell surface of cultured epithelial cell lines and dominantly localizes to epithelia in human mucosal tissue. Functional studies employing a BPI-neutralizing antiserum revealed that surface BPI blocks endotoxin-mediated signaling in epithelia and kills Salmonella typhimurium. These studies identify a previously unappreciated "molecular shield" for protection of mucosal surfaces against Gram-negative bacteria and their endotoxin.

Original languageEnglish
Pages (from-to)3902-3907
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number6
DOIs
Publication statusPublished - 19 Mar 2002
Externally publishedYes

Keywords

  • Eicosanoid
  • Infection
  • Inflammation
  • Mucosa

Fingerprint

Dive into the research topics of 'Lipid mediator-induced expression of bactericidal/permeability-increasing protein (BPI) in human mucosal epithelia'. Together they form a unique fingerprint.

Cite this