Release of gelatinase from a novel secretory compartment of human neutrophils.
Gelatinase is a metallo-proteinase that acts specifically on denatured collagen. In human neutrophils, this enzyme is localized in small, morphologically still unidentified storage organelles that are resolved from the specific and the azurophil granules upon subcellular fractionation by differential sedimentation. When neutrophils isolated from freshly drawn blood are exposed to soluble stimuli such as N-formyl-methionyl-leucyl-phenylalanine, zymosan-activated serum, phorbol myristate acetate, or the calcium ionophore A 23187, or are induced to phagocytose opsonized zymosan, they rapidly release gelatinase in large amounts (30-70% of the cellular content in 10 min). When neutrophils from donor blood, which had been stored for 24 h at 4 degrees C are used, extensive release even occurs without added stimuli by simply warming to 37 degrees C. Gelatinase release appears to occur by secretion because it is not dependent on phagocytosis. It is paralelled by the release of specific granule contents (vitamin B(12)-binding protein), but is more rapid and much more extensive. It is, however, dissociated from the discharge of azurophil granules (as assessed by beta-glucuronidase). In addition, it was found that gelatinase release does not depend on the activation of the respiratory burst, although the two responses are often observed in parallel. Release is not due to cell damage as the cytoplasmic enzyme lactate dehydrogenase is fully retained. The distinct subcellular distribution and kinetics of release of gelatinase reported in this paper uncover a novel, truly secretory compartment of human neutrophils, which is highly responsive to stimulation. Gelatinase and possibly other enzymes stored in this secretory organelle may be involved in the early events of neutrophil mobilization, the response to chemotactic signals and diapedesis.
D000001:Calcimycin / Q000494:pharmacology; D002352:Carrier Proteins / Q000302:isolation & purification; D002451:Cell Compartmentation; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000502:physiology; D005089:Exocytosis / Q000187:drug effects; D018093:Gelatinases; D006801:Humans; D009239:N-Formylmethionine / Q000031:analogs & derivatives / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils / Q000201:enzymology*; D009842:Oligopeptides / Q000494:pharmacology; D010434:Pepsin A / Q000302:isolation & purification / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014805:Vitamin B 12 / Q000378:metabolism
D002352:Carrier Proteins; D009842:Oligopeptides; D013481:Superoxides; D000001:Calcimycin; D003571:Cytochalasin B; D009239:N-Formylmethionine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010434:Pepsin A; D018093:Gelatinases; D013755:Tetradecanoylphorbol Acetate; D014805:Vitamin B 12