{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T12:39:02Z","timestamp":1760099942466},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2005,11,22]],"date-time":"2005-11-22T00:00:00Z","timestamp":1132617600000},"content-version":"vor","delay-in-days":5166,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[1991,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Previously, we reported that exposure of bone marrow\u2010derived macrophages (M\u03a6) to a phagocytic stimulus in the simultaneous presence of interferon\u2010\u03b3 (IFN\u2010\u03b3) induced these cells to generate nitrite (NO<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup>). This effect was achieved using both living (<jats:italic>i.e.<\/jats:italic> promastigotes of the protozoan parasite <jats:italic>Leishmania enriett\u00fc<\/jats:italic>) and inert (latex beads) particles. When the phagocytic stimulus was Leishmania, enhanced intracellular killing accompanied elevated NO<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup> secretion. As shown here, the capacity of phagocytosis to elicit NO<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup> production by IFN\u2010\u03b3\u2010treated M\u03a8 was inhibited by antibody to murine recombinant tumor necrosis factor\u2010\u03b1 (rTNF\u2010\u03b1), suggesting that phagocytosis enabled IFN\u2010\u03b3 to activate M\u03a8 via the induction of TNF\u2010\u03b1 as an autocrine second signal, M\u03d5 NO<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup> production in response to rIFN\u2010\u03b3 and either exogenous TNF\u2010\u03b1 or Leishmania was strongly enhanced by prostaglandin E<jats:sub>2<\/jats:sub>, consistent with such a mechanism, However, addition of either Leishmania promastigotes or latex beads to M\u03d5 cultures simultaneously exposed to both IFN\u2010\u03b3 and exogenous murine or human rTNF\u2010\u03b1 further potentiated activation as measured by NO<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup> release. Furthermore, anti\u2010TNF antibody failed to inhibit M\u03d5 responses to rIFN\u2010\u03b3 and bacterial lipopolysaccharide (LPS) in the presence or absence of Leishmania; also exogenous rTNF\u2010\u03b1 did not significantly affect NO<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup> production by IFN\u2010\u03b3\/LPS cultures despite a strong enhancement by Leishmania. These results suggest that phagocytosis enhances M\u03d5 responses by a process more complex than the sole induction of TNF\u2010\u03b1. Phagocytosis also increased M\u03d5 NO<jats:sub>2<\/jats:sub><jats:sup>\u2212<\/jats:sup> production elicted by IFN\u2010\u03b3 plus TNF\u2010\u03b1 in L\u2010arginine\u2010deficient media. These results indicate that phagocytosis may be an important mechanism of up\u2010regulating M\u03d5 microbicidal activity, and could be particularly relevant upon arginine depletion which occurs during an inflammatory response.<\/jats:p>","DOI":"10.1002\/eji.1830211036","type":"journal-article","created":{"date-parts":[[2007,3,9]],"date-time":"2007-03-09T10:48:49Z","timestamp":1173437329000},"page":"2553-2558","source":"Crossref","is-referenced-by-count":38,"title":["Phagocytosis enhances murine macrophage activation by interferon\u2010\u03b3 and tumor necrosis factor\u2010\u03b1"],"prefix":"10.1002","volume":"21","author":[{"given":"Sally Betz","family":"Corradin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yolande","family":"Buchm\u00fcller\u2010Rouiller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques","family":"Mau\u00ebl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,11,22]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.126.5.1863"},{"key":"e_1_2_1_3_2","first-page":"147","volume":"13","author":"Nacy C. 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