{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:48:11Z","timestamp":1790772491690,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2004,5,4]],"date-time":"2004-05-04T00:00:00Z","timestamp":1083628800000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2004,5]]},"abstract":"<jats:p><jats:bold>Abstract:\u2002<\/jats:bold> Circulating human neutrophils from patients with severe inflammatory disorders such as erysipelas and sepsis are specifically desensitized to complement factor C5a stimulation but not to stimulation with other stimuli like <jats:italic>N<\/jats:italic>\u2010formyl\u2010methionyl\u2010leucyl\u2010phenylalanine (FMLP), interleukin\u20108 (IL\u20108), leukotriene B<jats:sub>4<\/jats:sub> (LTB<jats:sub>4<\/jats:sub>), or platelet\u2010activating factor (PAF, 1\u2010<jats:italic>O<\/jats:italic>\u2010alkyl\u20102\u2010acetyl\u2010sn\u2010glycero\u20103\u2010phosphocholine). In this study, we raised the question whether factors released from polymorphonuclear leukocytes (PMNs) can specifically down\u2010regulate C5a\u2010dependent neutrophil functions.<\/jats:p><jats:p>When neutrophils were preincubated with either neutrophil lysates or neutrophil degranulation supernatants, a complete inhibition of C5a\u2010stimulated \u03b2\u2010glucuronidase release and chemotaxis could be observed, whereas FMLP\u2010, IL\u20108\u2010, LTB<jats:sub>4<\/jats:sub>\u2010 or PAF\u2010dependent functions were not affected. Serine protease inhibitors like phenylmethylsulfonyl fluoride, antileukoprotease, or elafin abolished this effect. High\u2010performance liquid chromatography of neutrophil degranulation supernatants revealed pronounced inhibition of C5a\u2010dependent neutrophil functions in fractions exerting elastase or cathepsin G activity, but not in fractions exerting proteinase 3 activity. Using purified human leukocyte elastase (HLE), C5a responses like intracellular calcium influx, \u03b2\u2010glucuronidase release, and chemotaxis were also specifically inhibited.<\/jats:p><jats:p>Our experiments show that the release of HLE or cathepsin G from neutrophils specifically down\u2010regulates the responsiveness of neutrophils to C5a. Elastase and cathepsin G may therefore play an important role in the down\u2010regulation of acute inflammation.<\/jats:p>","DOI":"10.1111\/j.0906-6705.2004.00145.x","type":"journal-article","created":{"date-parts":[[2004,5,4]],"date-time":"2004-05-04T11:06:16Z","timestamp":1083668776000},"page":"316-325","source":"Crossref","is-referenced-by-count":37,"title":["Human leukocyte elastase and cathepsin G are specific inhibitors of C5a\u2010dependent neutrophil enzyme release and 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