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In these situations release and\/or activation of cytokines may be different from that seen in response to a systemic stimulus, particularly because associations of various cell populations in these foci allows for the exposure of procytokines to the proteolytic enzymes produced by activated neutrophils, neutrophil elastase (NE), proteinase 3 (PR3), and cathepsin G (Cat G). To investigate the possibility of alternative processing of TNF\u03b1 and\/or IL-1\u03b2 by neutrophil-derived proteinases, immunoreactive TNF\u03b1 and IL-1\u03b2 release from lipopolysaccharide-stimulated THP-1 cells was measured in the presence of activated human neutrophils. Under these conditions, TNF\u03b1 and IL-1\u03b2 release was augmented 2- to 5-fold. In the presence of a specific inhibitor of NE and PR3, enhanced release of both cytokines was largely abolished; however, in the presence of a NE and Cat G selective inhibitor, secretory leucocyte proteinase inhibitor, reduction of the enhanced release was minimal. This finding suggested that the augmented release was attributable to PR3 but not NE nor Cat G. Use of purified enzymes confirmed this conclusion. These results indicate that there may be alternative pathways for the production of these two proinflammatory cytokines, particularly in the context of local inflammatory processes.<\/jats:p>","DOI":"10.1073\/pnas.96.11.6261","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:35:07Z","timestamp":1027694107000},"page":"6261-6266","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":295,"title":["Converting enzyme-independent release of tumor necrosis factor \u03b1 and IL-1\u03b2 from a stimulated human monocytic cell line in the presence of activated neutrophils or purified proteinase 3"],"prefix":"10.1073","volume":"96","author":[{"given":"Claire","family":"Coeshott","sequence":"first","affiliation":[{"name":"Cortech, Inc., 6850 North Broadway, Denver, CO 80221"}]},{"given":"Christie","family":"Ohnemus","sequence":"additional","affiliation":[{"name":"Cortech, Inc., 6850 North Broadway, Denver, CO 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