The macrophage-derived neutrophil chemotactic factor, MNCF: a lectin with TNF-alpha-like activities on neutrophils.
The macrophage-derived neutrophil chemotactic factor (MNCF) is an alpha-galactoside-binding lectin, known to induce dexamethasone-insensitive neutrophil recruitment. We further characterized MNCF effects on neutrophils and showed that it shares with TNF-alpha the ability to delay apoptosis and to trigger degranulation. MNCF and TNF-alpha 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.
Toledo
Karina Alves
KA
Departamento Biologia Celular Molecular, FMRP/Universidade de São Paulo, 14049900, Ribeirão Preto, Brazil.
Pereira
Fernando Lourenço
FL
Mambole
Agnès
A
Lesavre
Philippe
P
Roque-Barreira
Maria Cristina
MC
Halbwachs-Mecarelli
Lise
L
D000818:Animals; D015550:Cell Degranulation; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D037502:Galectin 3 / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology* / Q000494:pharmacology; D037102:Lectins / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology
D037502:Galectin 3; D016209:Interleukin-8; D037102:Lectins; D014409:Tumor Necrosis Factor-alpha