Comparison of properties of membrane bound versus soluble forms of human leukocytic elastase and cathepsin G.
Stimulation of human neutrophils with micromolar concentrations of N-formyl-methionyl-leucyl-phenyl-alanine (fMLP) or 4 beta-phorbol-12 beta-myristate-13 alpha-acetate (PMA), results in their degranulation and/or lysis with a concomitant release of Human Leucocyte Elastase (HLE; EC 3.4.21.37), Cathepsin G (cat G; EC 3.4.21.20) and Myeloperoxidase (MPO; EC 1.11.1.7) into the surrounding medium, some of which re-bind in an active form to neutrophil plasma membranes or membrane fragments. Histones, when present in the medium, prevent this association indicating that it is largely charge dependent. Bound proteinases have an increased resistance to inhibition by protein proteinase inhibitors, while bound MPO retains its ability to oxidatively inactivate alpha-1-proteinase inhibitor (alpha-1-PI). The attachment of oxidases and proteinases to plasma membrane or its fragments may allow them to remain active in an environment replete with proteinase inhibitors and, therefore, may be responsible for neutrophil or neutrophil-debris mediated tissue damage.
Bangalore
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American Red Cross Holland Laboratory, Rockville, MD 20855.
Travis
J
J
D000595:Amino Acid Sequence; D056649:Cathepsin G; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000201:enzymology; D006657:Histones / Q000494:pharmacology; D006801:Humans; D019272:Leukocyte Elastase; D008969:Molecular Sequence Data; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D011479:Protamines / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000494:pharmacology
D006657:Histones; D011479:Protamines; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; D012965:Sodium Chloride; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009195:Peroxidase; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D013755:Tetradecanoylphorbol Acetate