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Evidences support a role for macrophage migration inhibitory factor (MIF) in a number of inflammatory diseases, but the triggering of its secretion and its physiopathological role upon IC deposition remain elusive. Herein, we show that human macrophages secreted MIF after IC recognition, which in turn controlled the secretion of TNF. Macrophages from Mif\u2212\/\u2212 mice produced smaller amounts of TNF when stimulated with IgG-opsonized erythrocytes than wild-type (WT) cells. Using passive reverse Arthus reaction in the peritoneum and lungs as a model for IC-induced inflammation, we demonstrated that Mif\u2212\/\u2212 mice had a milder response, observed by reduced neutrophil recruitment, vascular leakage, and secretion of TNF, MIP-2, and keratinocyte-derived chemokine compared with WT controls. Adoptive transfer of alveolar macrophages from WT to Mif\u2212\/\u2212 mice rescued pulmonary neutrophil recruitment and TNF production upon passive reverse Arthus reaction. Our study indicates that Arthus inflammatory reaction is largely dependent on MIF and poses macrophages as a source of the MIF released upon IC recognition. These results give experimental support to the proposition that blockade of MIF might constitute an adjunctive, therapeutic approach to IC disease.<\/jats:p>","DOI":"10.1189\/jlb.0108009","type":"journal-article","created":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T02:09:34Z","timestamp":1233626974000},"page":"855-861","source":"Crossref","is-referenced-by-count":23,"title":["Migration inhibitory factor (MIF) released by macrophages upon recognition of immune complexes is critical to inflammation in Arthus reaction"],"prefix":"10.1093","volume":"85","author":[{"given":"Claudia N","family":"Paiva","sequence":"first","affiliation":[{"name":"Departamento de Imunologia, Instituto de Microbiologia Prof. Paulo de G\u00f3es, Universidade Federal do Rio de Janeiro-UFRJ , Rio de Janeiro , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa H","family":"Arras","sequence":"additional","affiliation":[{"name":"Departamento de Imunologia, Instituto de Microbiologia Prof. Paulo de G\u00f3es, Universidade Federal do Rio de Janeiro-UFRJ , Rio de Janeiro , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth S","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"Departamento de Imunologia, Instituto de Microbiologia Prof. Paulo de G\u00f3es, Universidade Federal do Rio de Janeiro-UFRJ , Rio de Janeiro , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Let\u00edcia S","family":"Alves","sequence":"additional","affiliation":[{"name":"Departamento de Imunologia, Instituto de Microbiologia Prof. Paulo de G\u00f3es, Universidade Federal do Rio de Janeiro-UFRJ , Rio de Janeiro , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Paulo","family":"Lessa","sequence":"additional","affiliation":[{"name":"Departamento de Imunologia, Instituto de Microbiologia Prof. Paulo de G\u00f3es, Universidade Federal do Rio de Janeiro-UFRJ , Rio de Janeiro , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Helena","family":"Silva","sequence":"additional","affiliation":[{"name":"Departamento de Imunologia, Instituto de Microbiologia Prof. Paulo de G\u00f3es, Universidade Federal do Rio de Janeiro-UFRJ , Rio de Janeiro , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Ejzemberg","sequence":"additional","affiliation":[{"name":"Departamento de Imunologia, Instituto de Microbiologia Prof. Paulo de G\u00f3es, Universidade Federal do Rio de Janeiro-UFRJ , Rio de Janeiro , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e1udio","family":"Canetti","sequence":"additional","affiliation":[{"name":"Instituto de Biof\u00edsica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro-UFRJ , Rio de Janeiro , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo T","family":"Bozza","sequence":"additional","affiliation":[{"name":"Departamento de Imunologia, Instituto de Microbiologia Prof. Paulo de G\u00f3es, Universidade Federal do Rio de Janeiro-UFRJ , Rio de Janeiro , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,2,2]]},"reference":[{"key":"2023032712581781000_","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/nri1200","article-title":"Macrophage migration inhibitory factor: a regulator of innate immunity","volume":"3","author":"Calandra","year":"2003","journal-title":"Nat. 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