{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T08:14:43Z","timestamp":1761293683526},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[1994,8,1]],"date-time":"1994-08-01T00:00:00Z","timestamp":775699200000},"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":[[1994,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The effects of the carbocyclic nucleoside MDL 201,112 and the purine nucleoside adenosine on the interferon-\u03b3 (IFN-\u03b3)-induced priming of macrophages (mfs) for the respiratory burst and major histocompatibility class II (MHC class II) Ia+ antigen expression were compared. Priming of purified, peritoneal m\u03c6s from Lewis (LEW\/N) rats for 18 h with recombinant rat IFN-\u03b3 (rRaIFN-\u03b3) in the presence of either adenosine (100 \u03bcM) or MDL 201,112 (10 \u03bcM) resulted in a fourfold decrease in superoxide anion (02-) production after stimulation with opsonized zymosan. Both agents were effective even when added 2 or 4 h after rRaIFN-\u03b3 treatment. Peritoneal m\u03c6s from LEW\/N rats stimulated with LPS\/rRaIFN-\u03b3 were observed to secrete immunoreactive and bioactive TNF-\u03b1 over 18 h in vitro and this cytokine could be dose-dependently inhibited by MDL 201,112. MDL 201,112 did not bind to classical A1 or A2 receptors on rat brain homogenates. Physiological levels of adenosine deaminase, or treatment with the nucleoside transport inhibitor dipyridamole, reversed the effects of adenosine; however, these agents at physiological concentrations had little or no effect on the inhibition of 02- release mediated by MDL 201,112. Furthermore, incubation of LEW\/N m\u03c6s for 18 h in vitro with rRaIFN-\u03b3 resulted in significant enhancement of MHC class II Ia+ antigen expression, and these levels could be blocked by nearly 50% by either MDL 201,112 (10 \u03bcM) or adenosine (100 \u03bcM). MDL 201,112 and adenosine were also effective in decreasing m\u03c6 opsonized zymosan-stimulated 02- levels and MHC class II Ia+ antigen expression in vivo. The effects of MDL 201,112 on the down-regulation of heat-killed M. tuberculosis-activated LEW\/N m\u03c6 MHC class II Ia+ antigen expression in vitro appear to be mediated by a novel pathway, because there was no rank order of potency of ADO A1 or A2 agonist\/antagonists (CCPA, NECA, XAC, or CPT) in our in vitro system. In summary, our data provide compelling evidence that immunoregulatory carbocyclic nucleoside analogues such as MDL 201,112 or adenosine appear to regulate LEW\/N rat mf activation through novel molecular mechanisms and may have important therapeutic implications for acute and chronic inflammatory diseases. J. Leukoc. Biol. 56: 133\u2013144; 1994.<\/jats:p>","DOI":"10.1002\/jlb.56.2.133","type":"journal-article","created":{"date-parts":[[2018,1,12]],"date-time":"2018-01-12T19:41:36Z","timestamp":1515786096000},"page":"133-144","source":"Crossref","is-referenced-by-count":19,"title":["Effect of the carbocyclic nucleoside analogue MDL 201,112 on inhibition of interferon-<i>\u03b3<\/i>-induced priming of Lewis (LEW\/N) rat macrophages for enhanced respiratory burst and MHC class II Ia+ antigen expression"],"prefix":"10.1093","volume":"56","author":[{"given":"Carl K","family":"Edwards","sequence":"first","affiliation":[{"name":"Department of Immunology, Marion Merrell Dow Research Institute , Cincinnati, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynnetta M","family":"Watts","sequence":"additional","affiliation":[{"name":"Department of Immunology, Marion Merrell Dow Research Institute , Cincinnati, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J","family":"Parmely","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Molecular Genetics and Immunology, Kansas University Medical Center , Kansas City"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew D","family":"Linnik","sequence":"additional","affiliation":[{"name":"CNS Department of Research, and Marion Merrell Dow Research Institute , Cincinnati, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard E","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Marion Merrell Dow Research Institute , Indianapolis, Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R","family":"Borcherding","sequence":"additional","affiliation":[{"name":"Department of Discovery Chemistry, Marion Merrell Dow Research Institute , Cincinnati, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1994,8,1]]},"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjlb.56.2.133","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/56\/2\/133\/49771187\/jlb0133.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/56\/2\/133\/49771187\/jlb0133.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T05:21:51Z","timestamp":1681190511000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/56\/2\/133\/6978881"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,8,1]]},"references-count":0,"journal-issue":{"issue":"2","published-online":{"date-parts":[[1994,8,1]]},"published-print":{"date-parts":[[1994,8,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jlb.56.2.133","relation":{},"ISSN":["0741-5400","1938-3673"],"issn-type":[{"value":"0741-5400","type":"print"},{"value":"1938-3673","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1994,8]]},"published":{"date-parts":[[1994,8,1]]}}}