{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T22:28:43Z","timestamp":1762640923300},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2004,6,3]],"date-time":"2004-06-03T00:00:00Z","timestamp":1086220800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2004,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Rheumatoid arthritis (RA) is a chronic inflammatory condition characterized by a cellular influx and destruction of the joint architecture. Chemokines characteristically regulate leukocyte recruitment and activation. Chemokine (CC motif) receptor\u2013like 2 (CCRL2) is an orphan receptor with homology to other CC chemokine receptors. We undertook this study to examine CCRL2 expression in RA, cytokine regulation of expression, and the source of a putative ligand in an attempt to determine the role of this receptor during inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Expression of CCRL2 on joint\u2010infiltrating leukocytes was examined by immunocytochemistry. In vitro studies evaluated CCRL2 expression in primary neutrophils using Northern and Western blotting and reverse transcriptase\u2013polymerase chain reaction. HEK 293 cells expressing two splice variants of CCRL2 (HEK\/CCRL2A or HEK\/CCRL2B) were generated with a retroviral expression system, and their migration in response to fractions of synovial fluid (SF) from RA patients was examined using a 48\u2010well chamber.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CCRL2 expression was observed on all infiltrating neutrophils and on some macrophages obtained from the SF of 5 RA patients. In vitro studies of primary neutrophils revealed that CCRL2 messenger RNA (mRNA) was rapidly up\u2010regulated following stimulation with lipopolysaccharide (1 \u03bcg\/ml) or tumor necrosis factor (5 ng\/ml). The mRNA for both CCRL2A and CCRL2B were expressed in cytokine\u2010stimulated neutrophils. Cells expressing either of these splice variants migrated in response to a fraction of RA SF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CCRL2 expression is up\u2010regulated on synovial neutrophils of RA patients. Inflammatory products present in the SF activate this receptor, indicating that CCRL2 is a functional receptor that may be involved in the pathogenesis of RA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.20275","type":"journal-article","created":{"date-parts":[[2004,6,3]],"date-time":"2004-06-03T17:01:40Z","timestamp":1086282100000},"page":"1806-1814","source":"Crossref","is-referenced-by-count":62,"title":["Up\u2010regulated expression and activation of the orphan chemokine receptor, CCRL2, in rheumatoid arthritis"],"prefix":"10.1002","volume":"50","author":[{"given":"Carole L.","family":"Galligan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wataru","family":"Matsuyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiro","family":"Matsukawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Mizuta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R.","family":"Hodge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O. 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