A crucial role for TNF-alpha in mediating neutrophil influx induced by endogenously generated or exogenous chemokines, KC/CXCL1 and LIX/CXCL5
| Autor: | S M, Vieira, H P, Lemos, R, Grespan, M H, Napimoga, D, Dal-Secco, A, Freitas, T M, Cunha, W A, Verri, D A, Souza-Junior, M C, Jamur, K S, Fernandes, C, Oliver, J S, Silva, M M, Teixeira, F Q, Cunha |
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| Rok vydání: | 2009 |
| Předmět: |
Mice
Knockout Chemokine CXCL5 Mice Inbred BALB C Sulfonamides Neutrophils Tumor Necrosis Factor-alpha Chemokine CXCL1 Peritonitis Intercellular Adhesion Molecule-1 Research Papers Antibodies Receptors Interleukin-8B Receptors Interleukin-8A Mice Inbred C57BL Mice Receptors Tumor Necrosis Factor Type I Macrophages Peritoneal Animals Cattle Mast Cells Serum Albumin |
| Zdroj: | British journal of pharmacology. 158(3) |
| ISSN: | 1476-5381 |
| Popis: | 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.Neutrophil recruitment was assessed in immunized mice challenged with methylated bovine serum albumin, KC/CXCL1, LIX/CXCL5 or tumour necrosis factor (TNF)-alpha. 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.Antigen challenge induced dose- and time-dependent neutrophil recruitment and production of KC/CXCL1, LIX/CXCL5 and TNF-alpha, 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-alpha 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-alpha production, which were inhibited by reparixin or anti-TNF-alpha 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-alpha upon LIX/CXCL5 stimulation. Methylated bovine serum albumin induced expression of ICAM-1 on mesenteric vascular endothelium, which was inhibited by anti-TNF-alpha or anti-LIX/CXCL5.Following antigen challenge, CXCR2 ligands are produced and act on macrophages and mast cells triggering the production of TNF-alpha, which synergistically contribute to neutrophil recruitment through induction of the expression of ICAM-1. |
| Databáze: | OpenAIRE |
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