Elastase and cathepsin G of human monocytes. Quantification of cellular content, release in response to stimuli, and heterogeneity in elastase-mediated proteolytic activity.
Human peripheral blood monocytes contain human leukocyte elastase (HLE) and cathepsin G (CG), serine proteinases originally described in azurophil granules of polymorphonuclear neutrophils (PMN). Immunoreactive HLE and CG of freshly harvested monocytes have been quantified in this study; to begin to elucidate potential roles for these enzymes in extracellular events, release in response to stimuli has been measured, along with proteolytic activity of monocytes toward surface-bound proteins. Our results indicate that whole-cell extracts of monocytes contain approximately 6% of the amount of HLE as do extracts of comparable numbers of PMN. In response to PMA in vitro, monocytes released 39 to 53% of their content of HLE and CG within 60 min, a fractional release greater than that of PMN. Furthermore, when phorbol-stimulated monocytes were adherent to a fibronectin-coated surface, extensive HLE-mediated proteolysis of the surface-bound protein was observed. Proteolysis by such cells in the presence of proteinase inhibitors was of considerable interest, since a subpopulation (15 to 20% of the total) expressed marked but localized proteolytic activity, possibly escaping inhibition through contact-mediated mechanisms. These data indicate that a subpopulation of freshly harvested monocytes is rich in HLE and CG (serine proteinases traditionally associated with PMN), can promptly release HLE and CG in response to stimuli, and can utilize HLE for extracellular proteolysis. Monocyte-derived serine proteinases may participate in extracellular events formerly associated with PMN-derived HLE and CG.
Campbell
E J
EJ
Department of Medicine, Jewish Hospital, Washington University Medical Center, St. Louis, MO 63110.
Silverman
E K
EK
Campbell
M A
MA
D056649:Cathepsin G; D002403:Cathepsins / Q000097:blood*; D015550:Cell Degranulation; D005110:Extracellular Space / Q000201:enzymology; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D009000:Monocytes / Q000201:enzymology*; D009504:Neutrophils / Q000201:enzymology; D010196:Pancreatic Elastase / Q000097:blood*; D012697:Serine Endopeptidases
D005353:Fibronectins; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase