Neutrophil and pathogen proteinases versus proteinase-activated receptor-2 lung epithelial cells: more terminators than activators.
The proteinase-activated receptor-2 (PAR-2) is expressed by different lung cells, including bronchial and alveolar epithelial cells. Since its discovery in 1995, numerous in vivo and in vitro studies have demonstrated its involvement in lung inflammation, whether from infectious or allergic causes. However, its role is controversial because there is evidence of both pro- and anti-inflammatory activities. PARs, including PAR-2, display a unique activation process. Specific proteinases cleave the N-terminal extracellular domain at a particular site. The new N-terminal sequence functions as a tethered ligand and binds intramolecularly to activate the receptor. Recently, other specific proteinases have been shown to cleave the N-terminal exodomain at other sites, resulting in a disarming of the receptor. Some of these activating and disabling proteinases are produced by host cells and others by pathogens, and may be present in the airspaces under diverse pathophysiologic settings.
Unité de Défense Innée et Inflammation/Inserm E336, Institut Pasteur, Paris, F-75015 France. chignard@pasteur.fr
Michel
M
Chignard
Dominique
D
Pidard
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000821:virology; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000201:enzymology*; D010447:Peptide Hydrolases / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000201:enzymology; D044464:Receptor, PAR-2 / Q000378:metabolism / Q000502:physiology*; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology
D001426:Bacterial Proteins; D044464:Receptor, PAR-2; D010447:Peptide Hydrolases