Deposition of immune complexes (IC) triggers Fc gamma R-dependent inflammation, leading to tissue damage in rheumatoid arthritis, systemic lupus erythematous, immune glomerulonephritis, and several immune vasculitides. 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-/- 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-/- 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-/- 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.
Pesq. Vet. Bras. 32(9):917-921, setembro 2012 917 RESUMO.-[Identiϐicação sorológica de alérgenos de ácaros da poeira domiciliar em cães com dermatite atópica.] Antígenos de ácaros da poeira domiciliar são utilizados por décadas para diagnóstico de doenças alér-gicas em seres humanos e animais. O objetivo do presente trabalho foi identiϐicar proteínas alergênicas presentes em extratos de Dermatophagoides farinae e Blomia tropicalis através de "immunoblotting" utilizando-se soros de animais alérgicos e conjugado anti-IgE canina. A análise por "immunoblotting" dos antígenos presentes no extrato de D. farinae (FDA Allergenic), utilizando soros de dez animais alérgicos, mostrou que oito soros reconhecem uma banda com peso molecular de aproximadamente 102 kDa; oito soros duas bandas entre 52 e 76 kDa; cinco soros uma banda com aproximadamente 76 kDa; quatro soros uma ban- House dust mite antigens have been used for decades to diagnose allergic diseases in humans and animals. The objective of this study was to identify allergens in commercial Dermatophagoides farinae and Blomia tropicalis extracts by immunoblotting using sera from allergic dogs and anti-dog IgE conjugate. The analysis of antigens present in the D. farinae extract (FDA Allergenic) using sera from 10 dogs allergic to D. farinae showed that eight sera recognized a band of approximately 102 kDa, eight recognized two bands of 52 to 76 kDa, ϐive recognized one band of approximately 76 kDa, four recognized one band of 31 to 38 kDa, and two recognized one band of 12 to 17 kDa. Immunoblot assays of the B. tropicalis extract (FDA Allergenic) using sera from 10 animals allergic to B. tropicalis showed that ϐive sera recognized two bands of 52 to 76 kDa. These results demonstrate the importance of the two house dust mite species for the pathogenesis of canine atopic dermatitis in Brazil. In addition, the results indicate which allergens should be present in allergenic extracts used for diagnosis and allergen-speciϐic immunotherapy. da entre 31 e 38 kDa; e dois soros uma banda entre 12 e 17 kDa. A análise por "immunoblotting" dos antígenos do extrato de B. tropicalis (FDA Allergenic) mostrou que cinco soros reconhecem duas bandas com pesos moleculares entre 52 e 76 kDa. Esses resultados demonstram a importância dessas duas espécies de ácaros da poeira domiciliar na patogênese da dermatite atópica canina no Brasil, assim como indicam alérgenos que devem estar presentes nos extratos alergênicos utilizados para diagnóstico e imunoterapia alérgeno-especíϐica.
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