{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T15:32:41Z","timestamp":1791905561642,"version":"4.3.4"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2010,8,1]],"date-time":"2010-08-01T00:00:00Z","timestamp":1280620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The ATP-gated P2X7 receptor (P2X7R) is a promising therapeutic target in chronic inflammatory diseases with highly specific antagonists currently under clinical trials for rheumatoid arthritis. Anti-inflammatory actions of P2X7R antagonists are considered to result from inhibition of P2X7R-induced release of proinflammatory cytokines from activated macrophages. However, P2X7Rs are also expressed in resting macrophages, suggesting that P2X7R may also signal via cytokine-independent mechanisms involved in joint disease. In this study, we examined P2X7R function in resting human lung macrophages and mouse bone marrow-derived macrophages and found that ATP induced rapid release of the lysosomal cysteine proteases cathepsin B, K, L, and S and that was independent of the presence of the proinflammatory cytokines IL-1\u03b2 and IL-18. Cathepsins released into the medium were effective to degrade collagen extracellular matrix. ATP-induced cathepsin release was abolished by P2X7R antagonists, absent from P2X7R\u2212\/\u2212 mouse macrophages, and not associated with cell death. Our results suggest P2X7R activation may play a novel and direct role in tissue damage through release of cathepsins independently of its proinflammatory actions via IL-1 cytokines.<\/jats:p>","DOI":"10.4049\/jimmunol.1000436","type":"journal-article","created":{"date-parts":[[2010,7,16]],"date-time":"2010-07-16T22:11:44Z","timestamp":1279318304000},"page":"2611-2619","source":"Crossref","is-referenced-by-count":104,"title":["P2X7 Receptor-Mediated Release of Cathepsins from Macrophages Is a Cytokine-Independent Mechanism Potentially Involved in Joint Diseases"],"prefix":"10.1093","volume":"185","author":[{"given":"Gloria","family":"Lopez-Castejon","sequence":"first","affiliation":[{"name":"Faculty of Life Sciences, University of Manchester , Manchester"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Theaker","sequence":"additional","affiliation":[{"name":"Department of Bioscience, AstraZeneca , Loughborough ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Pelegrin","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, University of Manchester , Manchester"},{"name":"Inflammation and Experimental Surgery Group, University Hospital Virgen de la Arrixaca, Fundaci\u00f3n para la Formaci\u00f3n e Investigaci\u00f3n Sanitarias , Murcia ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D","family":"Clifton","sequence":"additional","affiliation":[{"name":"Department of Bioscience, AstraZeneca , Loughborough ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Braddock","sequence":"additional","affiliation":[{"name":"Department of Bioscience, AstraZeneca , Loughborough ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annmarie","family":"Surprenant","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, University of Manchester , Manchester"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,8,15]]},"reference":[{"key":"2025032411473092300_r1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1189\/jlb.0306164","article-title":"DAMPs, PAMPs and alarmins: all we need to know about danger","volume":"81","author":"Bianchi","year":"2007","journal-title":"J. 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