{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T08:40:57Z","timestamp":1762504857897},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2100,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2003,5]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Lipoxin (LX) A<jats:sub>4<\/jats:sub> and aspirin\u2010triggered\u2010LX (ATL) are endogenous lipid\u2010derived mediators that regulate leukocyte trafficking via specific LXA<jats:sub>4<\/jats:sub> receptors (ALX), and are involved in endogenous anti\u2010inflammation and resolution. Both LXA<jats:sub>4<\/jats:sub> and ATL are produced by rat tissues <jats:italic>in vitro<\/jats:italic> as well as <jats:italic>in vivo<\/jats:italic>. In rats, LXA<jats:sub>4<\/jats:sub> and ATL exhibit potent physiological and pathophysiological roles. Thus, we set out to determine whether ALX is expressed in rat tissues and its potential role in modulating leukocyte trafficking with LXA<jats:sub>4<\/jats:sub> and ATL.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In rats, a stable analog of ATL, when given intravenously with two consecutive doses at approximately 60 <jats:italic>\u03bc<\/jats:italic>g kg<jats:sup>\u22121<\/jats:sup> each injection, significantly inhibited neutrophil infiltration (\u223c43%) and protein extravasation (\u223c42%) in a casein\u2010induced peritonitis.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The rat orthologue of ALX was cloned from peripheral blood leukocytes encoding a putative G protein\u2010coupled receptor (GPCR). It gave \u223c74 and \u223c84% homology, respectively to the deduced amino\u2010acid sequences of the human and mouse ALX.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Tissue distribution analysis by RNase protection revealed that this rat receptor is expressed in tissues\/cells, where LXA<jats:sub>4<\/jats:sub> displays physiological and pathophysiological roles, namely, lung, kidney and leukocytes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The rat orthologue of ALX gave specific radioligand binding with [<jats:sup>3<\/jats:sup>H]LXA<jats:sub>4<\/jats:sub> and [<jats:sup>125<\/jats:sup>\u2010Tyr]\u2010annexin 1\u2010derived peptide with apparent <jats:italic>K<\/jats:italic><jats:sub>d<\/jats:sub> values of 5 and 820 n<jats:sc>M<\/jats:sc>, respectively, that are at levels comparable to those of the human ALX.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Activation of rat ALX inhibited tumor necrosis factor alpha\u2010mediated nuclear factor kappaB activity in a ligand\u2010dependent manner utilizing a luciferase reporter gene system.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Together, these results are the first demonstration of a rat ALX that is conserved in both structure and function suggesting that ALX plays key roles in regulating effector immune responses from murine to human species.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2003) <jats:bold>139<\/jats:bold>, 89\u201398. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705220\">10.1038\/sj.bjp.0705220<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705220","type":"journal-article","created":{"date-parts":[[2003,5,13]],"date-time":"2003-05-13T20:08:44Z","timestamp":1052856524000},"page":"89-98","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["A 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