Expression of BPI (bactericidal/permeability-increasing protein) in human mucosal epithelia.
Among the antimicrobial proteins and peptides of humans is the cationic 55 kDa bactericidal/permeability-increasing protein (BPI), which possesses antibacterial, endotoxin-neutralizing and opsonic activity against Gram-negative bacteria. Although identified originally as an abundant constituent of neutrophil granules, we have recently identified functional expression of BPI by human mucosal epithelia. BPI expression was markedly up-regulated by exposure of epithelia to lipoxins, endogenous anti-inflammatory eicosanoids that are generated in vivo in the context of aspirin treatment (aspirin-triggered lipoxins). Epithelial BPI was found to be surface expressed and fully functional, as measured by antibacterial activity against Salmonella typhimurium as well as lipopolysaccharide (LPS; endotoxin)-neutralizing activity. These results suggest a role for BPI as an effector of epithelial antibacterial activity and as a modulator of epithelial responses to LPS. Both BPI and the lipoxins are currently the subject of intensive biopharmaceutical development, raising the possibility that therapeutic use of BPI or modulation of epithelial BPI expression may be a useful adjunctive therapy for conditions in which epithelial inflammation is associated with Gram-negative infections and/or endotoxin.
Levy
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Children's Hospital of Boston, Boston, MA 02115, U.S.A. and Channing Laboratory, Boston, MA 02115, USA. olevy@rics.bwh.harvard.edu
Canny
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Serhan
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Colgan
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D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D044045:Lipoxins / Q000378:metabolism; D008565:Membrane Proteins; D008958:Models, Molecular; D009092:Mucous Membrane / Q000166:cytology; D011487:Protein Conformation
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D044045:Lipoxins; D008565:Membrane Proteins; C021623:bactericidal permeability increasing protein