The macrophage-derived neutrophil chemotactic factor, MNCF: a lectin with TNF-alpha-like activities on neutrophils |
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Authors: | Toledo Karina Alves Pereira Fernando Lourenço Mambole Agnès Lesavre Philippe Roque-Barreira Maria Cristina Halbwachs-Mecarelli Lise |
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Institution: | a Departamento Biologia Celular Molecular, FMRP/Universidade de São Paulo, 14049900, Ribeirão Preto, Brazil b INSERM U845, Université René Descartes, 161 rue de Sevres, 75015 Paris, France |
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Abstract: | The macrophage-derived neutrophil chemotactic factor (MNCF) is an α-galactoside-binding lectin, known to induce dexamethasone-insensitive neutrophil recruitment. We further characterized MNCF effects on neutrophils and showed that it shares with TNF-α the ability to delay apoptosis and to trigger degranulation. MNCF and TNF-α effects show similar kinetics and involve Src kinases and MAPKinases dependent pathways. They were, however, clearly distinguished, since the soluble TNF-receptor etanercept prevented TNF but not MNCF effects, while melibiose disaccharide inhibited MNCF but not TNF effects. Absorption of MNCF on detoxi-gel did not alter its properties, precluding an LPS contamination effect. By contrast, galectin-3 required LPS to activate neutrophils. Specific antibodies allowed to further demonstrate that MNCF and galectin-3 are two distinct molecules. Finally, MNCF- and IL-8-induced neutrophil activation differed by their kinetic and sensitivity to pertussis toxin. In conclusion, MNCF is a distinct neutrophil agonist, with pro-inflammatory activities involving its carbohydrate recognition domain. |
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Keywords: | Lectin MNCF TNF-α Neutrophil Degranulation Apoptosis p38 MAPKinase |
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