A crucial role for TNF-α in mediating neutrophil influx induced by endogenously generated or exogenous chemokines, KC/CXCL1 and LIX/CXCL5

被引：132
作者：
Vieira, S. M. [2 ]
Lemos, H. P.
Grespan, R.
Napimoga, M. H. [3 ]
Dal-Secco, D.
Freitas, A.
Cunha, T. M.
Verri, W. A., Jr.
Souza-Junior, D. A. [4 ]
Jamur, M. C. [4 ]
Fernandes, K. S.
Oliver, C. [4 ]
Silva, J. S. [5 ]
Teixeira, M. M. [6 ]
Cunha, F. Q. [1 ]
机构：
[1] Univ Sao Paulo, Dept Pharmacol, Fac Med Ribeirao Preto, Sch Med Ribeirao Preto, BR-14049900 Sao Paulo, Brazil
[2] Natl Inst Res Amazon INPA, Pharmacol Lab, Manaus, Amazonas, Brazil
[3] Univ Uberaba, Mol Biol Lab, Uberaba, Brazil
[4] Univ Sao Paulo, Dept Cell & Mol Biol, Sch Med Ribeirao Preto, BR-14049900 Sao Paulo, Brazil
[5] Univ Sao Paulo, Dept Biochem & Immunol, Sch Med Ribeirao Preto, BR-14049900 Sao Paulo, Brazil
[6] Univ Fed Minas Gerais, Dept Immunopharmacol Biochem & Immunol, ICB, Belo Horizonte, MG, Brazil
来源：
BRITISH JOURNAL OF PHARMACOLOGY | 2009年 / 158卷 / 03期
基金：
巴西圣保罗研究基金会;
关键词：
CXCR2; inflammation; chemokines; cytokines; leukocytes; neutrophil recruitment; TUMOR-NECROSIS-FACTOR; PLATELET-ACTIVATING-FACTOR; C-X-C; MAST-CELLS; LEUKOCYTE RECRUITMENT; ADHESION MOLECULES; LEUKOTRIENE B-4; EXPRESSION; MIGRATION; RECEPTOR;
D O I：
10.1111/j.1476-5381.2009.00367.x
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
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)-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. Key results: 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. Conclusion and implications: 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.
引用
收藏
页码：779 / 789
页数：11
相关论文
共 57 条
  • [31] Kasama Tsuyoshi, 2005, Current Drug Targets - Inflammation and Allergy, V4, P273, DOI 10.2174/1568010054022114
  • [32] Koch AE, 2001, ARTHRITIS RHEUM-US, V44, P31, DOI 10.1002/1529-0131(200101)44:1<31::AID-ANR5>3.0.CO
  • [33] 2-4
  • [34] IL-23 and TH17-mediated inflammation in human allergic contact dermatitis[J]. Larsen, Jeppe Madura;Bonefeld, Charlotte Menne;Poulsen, Steen Seier;Geisler, Carsten;Skov, Lone. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2009(02)
  • [35] Chemokines - Chemotactic cytokines that mediate inflammation[J]. Luster, AD. NEW ENGLAND JOURNAL OF MEDICINE, 1998(07)
  • [36] Regulation of early peritoneal neutrophil migration by macrophage inflammatory protein-2 and mast cells in experimental peritonitis[J]. Mercer-Jones, MA;Shrotri, MS;Heinzelmann, M;Peyton, JC;Cheadle, WG. JOURNAL OF LEUKOCYTE BIOLOGY, 1999(02)
  • [37] A homolog of the human chemokine receptor CXCR1 is expressed in the mouse[J]. Moepps, B;Nuesseler, E;Braun, M;Gierschik, P. MOLECULAR IMMUNOLOGY, 2006(07)
  • [38] Neutrophil migration induced by IL-1β depends upon LTB4 released by macrophages and upon TNF-α and IL-1β released by mast cells[J]. Oliveira, S. H. P.;Canetti, C.;Ribeiro, R. A.;Cunha, F. Q. INFLAMMATION, 2008(01)
  • [39] Tumour necrosis factor (TNF)-α primes murine neutrophils when triggered via formyl peptide receptor-related sequence 2, the murine orthologue of human formyl peptide receptor-like 1, through a process involving the type I TNF receptor and subcellular granule mobilization[J]. Onnheim, Karin;Bylund, Johan;Boulay, Francois;Dahlgren, Claes;Forsman, Huamei. IMMUNOLOGY, 2008(04)
  • [40] Papi Alberto, 2006, Proc Am Thorac Soc, V3, P245, DOI 10.1513/pats.200512-125SF
123456