{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:52:31Z","timestamp":1760921551910,"version":"3.38.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T00:00:00Z","timestamp":1433116800000},"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":[[2015,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Miltefosine [hexadecylphosphocholine (HPC)] is the only orally bioavailable drug for the disease visceral leishmaniasis, which is caused by the protozoan parasite Leishmania donovani. Although miltefosine has direct leishmanicidal effects, evidence is mounting for its immune system\u2013dependent effects. The mechanism of such indirect antileishmanial effects of miltefosine remains to be discovered. As platelet-activating factor and HPC share structural semblances and both induce killing of intracellular Leishmania, we surmised that platelet-activating factor (PAF) receptor had a significant role in the antileishmanial function of miltefosine. The proposition was supported by molecular dynamic simulation of HPC docking into PAF receptor and by comparison of its leishmanicidal function on PAF receptor\u2013deficient macrophages and mice under HPC treatment. We observed that compared with wild-type macrophages, the PAF receptor\u2013deficient macrophages showed 1) reduced binding of a fluorescent analog of HPC, 2) decreased TNF-\u03b1 production, and 3) lower miltefosine-induced killing of L. donovani. Miltefosine exhibited significantly compromised leishmanicidal function in PAF receptor\u2013deficient mice. An anti-PAF receptor Ab led to a significant decrease in miltefosine-induced intracellular Leishmania killing and IFN-\u03b3 production in a macrophage\u2013T cell coculture system. These results indicate significant roles for PAF receptor in the leishmanicidal activity of HPC. The findings open new avenues for a more rational understanding of the mechanism of action of this drug as well as for improved therapeutic strategies.<\/jats:p>","DOI":"10.4049\/jimmunol.1401890","type":"journal-article","created":{"date-parts":[[2015,5,16]],"date-time":"2015-05-16T03:15:33Z","timestamp":1431746133000},"page":"5961-5967","source":"Crossref","is-referenced-by-count":7,"title":["Platelet-Activating Factor Receptor Contributes to Antileishmanial Function of Miltefosine"],"prefix":"10.1093","volume":"194","author":[{"given":"Pallavi R","family":"Gangalum","sequence":"first","affiliation":[{"name":"National Centre for Cell Science , Ganeshkhind, Pune 411007 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waldion\u00ea","family":"de Castro","sequence":"additional","affiliation":[{"name":"Nucleo de Pesquisa em Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Ouro Preto , CEP 35400-000 Ouro Preto ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leda Q","family":"Vieira","sequence":"additional","affiliation":[{"name":"Nucleo de Pesquisa em Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Ouro Preto , CEP 35400-000 Ouro Preto ,","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ranadhir","family":"Dey","sequence":"additional","affiliation":[{"name":"Bose Institute , Kolkata 700 054 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Rivas","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u00f3gicas, Consejo Superior de Investigaciones Cientificas, Unidad Metabol\u00f3mica, Interacciones y Bioan\u00e1lisis, Universidad CEU San Pablo , 28040 Madrid ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shailza","family":"Singh","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science , Ganeshkhind, Pune 411007 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subrata","family":"Majumdar","sequence":"additional","affiliation":[{"name":"Bose Institute , Kolkata 700 054 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bhaskar","family":"Saha","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science , Ganeshkhind, Pune 411007 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,6,15]]},"reference":[{"key":"2025030706504343200_r1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.2165\/00128071-200203020-00003","article-title":"Leishmaniasis: recognition and management with a focus on the immunocompromised patient","volume":"3","author":"Choi","year":"2002","journal-title":"Am. 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