Lipid mediator-induced expression of bactericidal/ permeability-increasing protein (BPI) in human mucosal epithelia.
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 anti-serum 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.
Canny
Geraldine
G
Department of Veterinary Physiology, University College of Dublin, Dublin 4, Ireland.
Levy
Ofer
O
Furuta
Glenn T
GT
Narravula-Alipati
Sailaja
S
Sisson
Richard B
RB
Serhan
Charles N
CN
Colgan
Sean P
SP
D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D018938:Caco-2 Cells; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008055:Lipids / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D008565:Membrane Proteins; D009092:Mucous Membrane / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D021381:Protein Transport; D012486:Salmonella typhimurium / Q000502:physiology
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D008055:Lipids; D008070:Lipopolysaccharides; D008565:Membrane Proteins; C021623:bactericidal permeability increasing protein