Chemotactic factor inactivators of human granulocytes.
During phagocytosis, neutrophils release a variety of substances that include activators and inactivators of chemotactic factors. It is generally considered that these represent hydrolytic enzymes. Elastase and cathepsin G, major proteases released from lysosomal granules during phagocytosis, contain broad hydrolytic activity. This study examined granule elastase and cathepsin G for their role as inactivators of chemotactic factors. Elastase and cathepsin G were purified from human neutrophils by Trasylol-Sepharose and CM-cellulose chromatography. Small amounts (approximately equal to 3 microgram, 1 muM) of elastase and cathepsin G, comparable to quantities released by 10(6) neutrophils during phagocytosis, completely inactivated the C5 chemotactic factor generated in human serum. Larger concentrations were needed to inactivate the C3 chemotactic factor, and when the bacterial chemotactic factor from Escherichia coli was employed, five times more elastase or cathepsin G was ineffective against this chemotactic factor. Supernatant fluid from human neutrophils that had ingested complement-coated zymosan particles contained elastase and cathepsin G and had inactivator activity for both the C5 chemotactic fragment and the bacterial factor. A specific inhibitor of elastase largely abolished the inactivator activity in the phagocytic supernates that was directed against C5 factor but did not affect the inactivator activity for the bacterial factor. Similar results occurred in studies of granule lysates. These data indicate heterogeneity in the chemotactic factor inactivator activity released by phagocytosing neutrophils. The predominant inactivator activity of the C5 chemotactic fragment is attributable to elastase and cathepsin G.
D002403:Cathepsins / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002845:Chromatography; D003864:Depression, Chemical; D004926:Escherichia coli; D006098:Granulocytes / Q000187:drug effects; D006801:Humans; D007962:Leukocytes / Q000187:drug effects; D009504:Neutrophils / Q000378:metabolism; D010196:Pancreatic Elastase / Q000494:pharmacology*
D002403:Cathepsins; D010196:Pancreatic Elastase