Bactericidal mechanisms of the human neutrophil. An integrated biochemical and morphological model.
The bactericidal activity of the human neutrophil is dependent on a coordinated series of events by which the bacteria become confined to a vacuole. Fusion of the azurophil and specific granules with the phagocytic vacuole results in secretion of BPI, the primary oxygen independent bactericidal protein, and of myeloperoxidase into the phagolysosome. Simultaneously, an electron transport chain, the NADPH oxidase, is activated in the membrane of the phagolysosome, resulting in generation of H2O2, which together with myeloperoxidase and Cl- forms a highly bactericidal agent. Digestion of the killed bacteria is subsequently effectuated by proteases and lipases of the neutrophil granules. The neutrophil thus has several highly efficient bactericidal systems that overlap to a certain degree, thereby giving the neutrophil an overcapacity to kill. This is appreciated in the defence against microorganisms, but is increasingly being recognized as a cause of perturbation of serum protease anti-protease homeostasis that may cause major tissue destruction. The recent achievements in the understanding of neutrophil function will hopefully permit better control to be exerted over this potent cell.
D023181:Antimicrobial Cationic Peptides; D001770:Blood Bactericidal Activity; D001798:Blood Proteins / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D006105:Granulomatous Disease, Chronic / Q000276:immunology; D006801:Humans; D008565:Membrane Proteins; D008954:Models, Biological; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019255:NADPH Oxidases; D009504:Neutrophils / Q000276:immunology*; D010101:Oxygen Consumption; D010428:Pentosephosphates / Q000378:metabolism; D010539:Permeability; D009195:Peroxidase / Q000378:metabolism; D010587:Phagocytosis; D014617:Vacuoles / Q000276:immunology
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D008565:Membrane Proteins; D010428:Pentosephosphates; C021623:bactericidal permeability increasing protein; D009195:Peroxidase; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases