Mast cell proteoglycans modulate the secretagogue, proteoglycanase, and amidolytic activities of dog mast cell chymase.
Chymase, a potent secretagogue for airway gland serous cells, is stored in secretory granules and released from mast cells together with proteoglycans. To investigate the hypothesis tha tproteoglycans modulate chymase-induced effects, we studied the influence of proteoglycans purified from dog mastocytoma cells on chymase-induced secretion from cultured bovine airway gland serous cells. Heparin proteoglycans reduced the chymase-induced secretory response, whereas glycosaminoglycans and chondroitin sulfate proteoglycans had less of an effect. Chymase released together with proteoglycans from activated mast cells caused secretion comparable to that caused by purified chymase reconstituted with purified proteoglycans. Despite partial inhibition by exocytosed proteoglycans, the secretagogue activity of chymase remains substantial compared to that of histamine. However, proteoglycans virtually abolished chymase-induced degradation of the products of serous cell secretion. Although the secretagogue and proteoglycanase activities of chymase are inhibited by most classes of mast cell granule-associated glycans, the amidolytic activity of chymase toward tripeptide 4-nitroanilide substrates is augmented. These findings suggest that mast cell proteoglycans modulate the secretagogue, proteoglycanase, and peptidase activity of chymase, and the results predict that the extent of this modulation in vivo depends on the nature of the proteoglycans with which chymase is released from mast cells.
Sommerhoff
C P
CP
Cardiovascular Research Institute, University of California, San Francisco 94143-0911.
Ruoss
S J
SJ
Caughey
G H
GH
D000818:Animals; D002457:Cell Extracts; D011508:Chondroitin Sulfate Proteoglycans / Q000494:pharmacology; D002850:Chromatography, Gel; D053818:Chymases; D004285:Dogs; D006493:Heparin / Q000031:analogs & derivatives / Q000494:pharmacology; D008407:Mast Cells / Q000378:metabolism*; D012515:Mast-Cell Sarcoma / Q000378:metabolism; D011509:Proteoglycans / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000502:physiology*; D012704:Serous Membrane / Q000378:metabolism; D014132:Trachea / Q000378:metabolism
D002457:Cell Extracts; D011508:Chondroitin Sulfate Proteoglycans; D011509:Proteoglycans; C036090:heparin proteoglycan; D006493:Heparin; D012697:Serine Endopeptidases; D053818:Chymases