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Title: A crucial role for TNF-α in mediating neutrophil influx induced by endogenously generated or exogenous chemokines, KC/CXCL1 and LIX/CXCL5: RESEARCH PAPER
Authors: Manfredo Vieira, Silvio
Lemos, Henrique Paula
Grespan, Renata
Napimoga, Marcelo Henrique
Dal-Secco, Daniela
Freitas, Andressa de
Cunha, Thiago Mattar
Verri, Waldiceu A.
Souza, Devandir Antonio
Jamur, Maria Célia
Fernandes, Karla S.
Oliver, Constance
Silva, Joäo Santana da
Teixeira, Mauro Martins
Cunha, Fernando Queiroz
Keywords: 3 [3 Tert Butylthio 1 (4 Chlorobenzyl) 5 Isopropyl 2 Indolyl] 2,2 Dimethylpropionic Acid
Serum Albumin, Bovine
Chemokine Receptor Antagonist
Chemokine Receptor Ccr2
Chemokine Receptor Cxcr1
Chemokine Receptor Cxcr2
Cromoglycate Disodium
Cxcl1 Chemokine
Cxcl1 Chemokine Antibody
Cxcl2 Chemokine
Cytokine Antibody
Epithelial Derived Neutrophil Activating Factor 78
Epithelial Derived Neutrophil Activating Factor 78 Antibody
Intercellular Adhesion Molecule-1
Stabilizing Agent
Tumor Necrosis Factor-alpha
Tumor Necrosis Factor Alpha Antibody
Tumor Necrosis Factor Receptor 1
Unclassified Drug
Animals Cell
Animals Experiment
Animals Model
Animals Tissue
Confocal Microscopy
Controlled Study
Dose Time Effect Relation
Enzyme-linked Immunosorbent Assay
Mast Cell
Mesenteric Vein
Neutrophil Chemotaxis
Peritoneum Exudate
Priority Journal
Protein Expression
Vascular Endothelium
Cxcl1 Chemokine
Chemokine Cxcl5
Intercellular Adhesion Molecule-1
Macrophages, Peritoneal
Mast Cells
Mice, Inbred Balb C
Mice, Inbred C57bl
Mice, Knockout
Receptors, Interleukin-8a
Receptors, Interleukin-8b
Receptors, Tumor Necrosis Factor, Type I
Serum Albumin
Tumor Necrosis Factor-alpha
Issue Date: 2009
metadata.dc.publisher.journal: British Journal of Pharmacology
metadata.dc.relation.ispartof: Volume 158, Número 3, Pags. 779-789
Abstract: Background and purpose: Chemokines orchestrate neutrophil recruitment to inflammatory foci. In the present study, we evaluated the participation of three chemokines, KC/CXCL1, MIP-2/CXCL2 and LIX/CXCL5, which are ligands for chemokine receptor 2 (CXCR2), in mediating neutrophil recruitment in immune inflammation induced by antigen in immunized mice. Experimental approach: Neutrophil recruitment was assessed in immunized mice challenged with methylated bovine serum albumin, KC/CXCL1, LIX/CXCL5 or tumour necrosis factor (TNF)-α. Cytokine and chemokine levels were determined in peritoneal exudates and in supernatants of macrophages and mast cells by elisa. CXCR2 and intercellular adhesion molecule 1 (ICAM-1) expression was determined using immunohistochemistry and confocal microscopy. Key results: Antigen challenge induced dose- and time-dependent neutrophil recruitment and production of KC/CXCL1, LIX/CXCL5 and TNF-α, but not MIP-2/CXCL2, in peritoneal exudates. Neutrophil recruitment was inhibited by treatment with reparixin (CXCR1/2 antagonist), anti-KC/CXCL1, anti-LIX/CXCL5 or anti-TNF-α antibodies and in tumour necrosis factor receptor 1-deficient mice. Intraperitoneal injection of KC/CXCL1 and LIX/CXCL5 induced dose- and time-dependent neutrophil recruitment and TNF-α production, which were inhibited by reparixin or anti-TNF-α treatment. Macrophages and mast cells expressed CXCR2 receptors. Increased macrophage numbers enhanced, while cromolyn sodium (mast cell stabilizer) diminished, LIX/CXCL5-induced neutrophil recruitment. Macrophages and mast cells from immunized mice produced TNF-α upon LIX/CXCL5 stimulation. Methylated bovine serum albumin induced expression of ICAM-1 on mesenteric vascular endothelium, which was inhibited by anti-TNF-α or anti-LIX/CXCL5. Conclusion and implications: Following antigen challenge, CXCR2 ligands are produced and act on macrophages and mast cells triggering the production of TNF-α, which synergistically contribute to neutrophil recruitment through induction of the expression of ICAM-1. © 2009 The British Pharmacological Society.
metadata.dc.identifier.doi: 10.1111/j.1476-5381.2009.00367.x
Appears in Collections:Artigos

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