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As reactive oxygen intermediates might play a role, we analyzed macrophages and mice lacking the gp91phoxsubunit of the phagocyte NADPH oxidase (phox) for their ability to combat an infection with <jats:italic>L.\u2004major<\/jats:italic>. Macrophages from wild\u2010type and gp91phox<jats:sup>\u2013\/\u2013<\/jats:sup> mice had an equal capacity to kill<jats:italic>L.\u2004major<\/jats:italic> after activation by cytokines. Unlike iNOS, the activity of phox was dispensable for the resolution of the acute skin lesions and exerted only a limited effect on the containment of the parasites in the draining lymph node, but was essential for the clearance of <jats:italic>L.\u2004major<\/jats:italic> in the spleen. During the chronic phase of infection, parasites persisted at high levels in gp91phox<jats:sup>\u2013\/\u2013<\/jats:sup> mice, and cutaneous lesions re\u2010emerged in approximately 60% of these mice. gp91phox deficiency did not impair the expression of iNOS or the production of TNF and IFN\u2010\u03b3. These results demonstrate that iNOS and phox are both required for the control of <jats:italic>L.\u2004major<\/jats:italic> <jats:italic>in vivo<\/jats:italic> and display unexpected organ\u2010 and stage\u2010specific anti\u2010leishmanial effects.<\/jats:p>","DOI":"10.1002\/eji.200323825","type":"journal-article","created":{"date-parts":[[2003,4,30]],"date-time":"2003-04-30T16:01:44Z","timestamp":1051718504000},"page":"1224-1234","source":"Crossref","is-referenced-by-count":79,"title":["Organ\u2010specific and stage\u2010dependent control of <i>Leishmania major<\/i> infection by inducible nitric oxide synthase and phagocyte NADPH oxidase"],"prefix":"10.1002","volume":"33","author":[{"given":"Martin","family":"Blos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Schleicher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.\u2004Janaina\u2004Soares","family":"Rocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udo","family":"Mei\u00dfner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"R\u00f6llinghoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Bogdan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,4,11]]},"reference":[{"key":"e_1_2_7_1_2","first-page":"361","article-title":"Nitric oxide in leishmaniasis: from antimicrobial activity to immunoregulation.\n In Fang, F. 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