Neutrophil elastase, proteinase 3 and cathepsin G: physicochemical properties, activity and physiopathological functions.
Polymorphonuclear neutrophils form a primary line of defense against bacterial infections using complementary oxidative and non-oxidative pathways to destroy phagocytized pathogens. The three serine proteases elastase, proteinase 3 and cathepsin G, are major components of the neutrophil primary granules that participate in the non-oxidative pathway of intracellular pathogen destruction. Neutrophil activation and degranulation results in the release of these proteases into the extracellular medium as proteolytically active enzymes, part of them remaining exposed at the cell surface. Extracellular neutrophil serine proteases also help kill bacteria and are involved in the degradation of extracellular matrix components during acute and chronic inflammation. But they are also important as specific regulators of the immune response, controlling cellular signaling through the processing of chemokines, modulating the cytokine network, and activating specific cell surface receptors. Neutrophil serine proteases are also involved in the pathogenicity of a variety of human diseases. This review focuses on the structural and functional properties of these proteases that may explain their specific biological roles, and facilitate their use as molecular targets for new therapeutic strategies.
Korkmaz
Brice
B
INSERM U618 "Protéases et Vectorisation Pulmonaires", Université François Rabelais, 10 Boulevard Tonnellé, BP 3223, 37032 Tours Cedex, France.
Moreau
Thierry
T
Gauthier
Francis
F
D000595:Amino Acid Sequence; D001665:Binding Sites; D056649:Cathepsin G; D002403:Cathepsins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000201:enzymology; D019272:Leukocyte Elastase / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D008969:Molecular Sequence Data; D053146:Myeloblastin / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D013379:Substrate Specificity
D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D019272:Leukocyte Elastase; D053146:Myeloblastin