{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T20:32:54Z","timestamp":1760646774903},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[1999,3,1]],"date-time":"1999-03-01T00:00:00Z","timestamp":920246400000},"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":[[1999,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We have previously shown that mitogenic activation of human PBMC rapidly increases both the intracellular phosphatidic acid (PA) level and cyclic nucleotide phosphodiesterase (PDE) activity, with time-course responses, suggesting a causative relationship between the two events. PA also directly stimulated cAMP-PDE activity in acellular systems. Thus the mitogenic properties of PA might be due to its ability to lower the level of cAMP, a negative effector of lymphocyte activation, through PDE activation. In this study, human PBMC were stimulated either with the mitogenic lectin ConA, the anti-CD3 mAb OKT3, or the phorbol ester TPA. All three agonists increased the radiolabeled PA level and the PA mass in treated cells and simultaneously increased cytosolic and particulate cAMP-and cGMP-PDE activities, with significant positive correlations between PA accumulation and PDE activities. Furthermore, the ConA-induced PDE activation was dose-dependently reduced by treatment of PBMC with the diacylglycerol-kinase inhibitor R59022. This compound also dose-dependently lowered the PA level and inhibited the proliferative response to ConA. In addition, TPA-induced PDE activation was totally abolished by ethanol, which strongly reduced PA accumulation in response to the phorbol ester. These data suggest that PA increase may be linked to mitogen-induced PDE activation. Experiments performed in the presence of rolipram indicated that ConA and TPA stimulated both the rolipram-sensitive PDE4 and the rolipram-insensitive PDE activities, OKT3 being more active on PDE4. All three agonists stimulated the cGMP-specific PDE5. These results suggest that PA is an important component of the mechanisms that maintain a low level of cyclic nucleotides, which is a prerequisite for an optimal lymphoproliferative response. J. Leukoc. Biol. 65: 381\u2013390; 1999.<\/jats:p>","DOI":"10.1002\/jlb.65.3.381","type":"journal-article","created":{"date-parts":[[2018,1,12]],"date-time":"2018-01-12T18:54:20Z","timestamp":1515783260000},"page":"381-390","source":"Crossref","is-referenced-by-count":15,"title":["Relationships between phosphatidic acid and cyclic nucleotide phosphodiesterases in activated human blood mononuclear cells"],"prefix":"10.1093","volume":"65","author":[{"given":"Alexia","family":"Zakaroff-Girard","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U352, Laboratoire de Biochimie et Pharmacologie, Institut National des Sciences Appliqu\u00e9es de Lyon , Villeurbanne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samer El","family":"Bawab","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U352, Laboratoire de Biochimie et Pharmacologie, Institut National des Sciences Appliqu\u00e9es de Lyon , Villeurbanne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georges","family":"N\u00e9moz","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U352, Laboratoire de Biochimie et Pharmacologie, Institut National des Sciences Appliqu\u00e9es de Lyon , Villeurbanne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Lagarde","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U352, Laboratoire de Biochimie et Pharmacologie, Institut National des Sciences Appliqu\u00e9es de Lyon , Villeurbanne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annie-France","family":"Prigent","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U352, Laboratoire de Biochimie et Pharmacologie, Institut National des Sciences Appliqu\u00e9es de Lyon , Villeurbanne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1999,3,1]]},"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjlb.65.3.381","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/65\/3\/381\/49731744\/jlb0381.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/65\/3\/381\/49731744\/jlb0381.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T04:30:27Z","timestamp":1680669027000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/65\/3\/381\/6976756"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,3,1]]},"references-count":0,"journal-issue":{"issue":"3","published-online":{"date-parts":[[1999,3,1]]},"published-print":{"date-parts":[[1999,3,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jlb.65.3.381","relation":{},"ISSN":["0741-5400","1938-3673"],"issn-type":[{"value":"0741-5400","type":"print"},{"value":"1938-3673","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1999,3]]},"published":{"date-parts":[[1999,3,1]]}}}