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Departments of
*
Pathology and
Internal Medicine, Division of Pulmonary and Critical Care, University of Michigan Medical School, Ann Arbor, MI 48109
We investigated the involvement of monocyte chemoattractant protein
(MCP)-1 in a murine model of septic peritonitis induced by cecal
ligation and puncture (CLP). Initial studies demonstrated that CLP
induced a dramatic increase in MCP-1 production in the peritoneum,
followed by an increase in the recruitment of leukocytes. MCP-1
blockade with anti-MCP-1 antiserum significantly decreased the
survival rate following CLP, which was accompanied by an enhanced
recovery of viable bacteria from the peritoneum. This was likely due to
the reduction in the recruitment and activation of both macrophages and
neutrophils. To understand the mechanisms whereby MCP-1 may influence
neutrophil infiltration, levels of chemokines known to attract
neutrophils were monitored, which showed that peritoneal levels of
macrophage-inflammatory protein (MIP)-2, KC, and MIP-1
were not
altered with anti-MCP-1 Abs. However, anti-MCP-1 Abs reduced
the peritoneal levels of leukotriene B4 (LTB4)
by 59%. The i.p. injection of MCP-1 into normal mice resulted in
elevated levels of LTB4 in the peritoneum. In vitro, MCP-1
stimulated the production of LTB4 from peritoneal
macrophages, in a dose-dependent manner. A specific LTB4
receptor antagonist (CP-105,696) inhibited CLP-induced recruitment of
both neutrophils and macrophages, which was accompanied by a reduced
level of MCP-1 in the peritoneum. Finally, administration of CP-105,696
was extremely detrimental to the survival of mice following CLP. These
experiments demonstrate that endogenous MCP-1 serves as an indirect
mediator to attract neutrophils via the production of LTB4,
and suggest the cross-talk can occur between MCP-1 and the lipid
mediator LTB4 during septic peritonitis.
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J. M. Schuh, K. Blease, and C. M. Hogaboam CXCR2 Is Necessary for the Development and Persistence of Chronic Fungal Asthma in Mice J. Immunol., February 1, 2002; 168(3): 1447 - 1456. [Abstract] [Full Text] [PDF]
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J. A. Jordan, R.-F. Guo, E. C. Yun, V. Sarma, R. L. Warner, L. D. Crouch, G. Senaldi, T. R. Ulich, and P. A. Ward Role of IL-18 in Acute Lung Inflammation J. Immunol., December 15, 2001; 167(12): 7060 - 7068. [Abstract] [Full Text] [PDF]
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P. W. Finn, J. R. Stone, M. R. Boothby, and D. L. Perkins Inhibition of NF-{kappa}B-Dependent T Cell Activation Abrogates Acute Allograft Rejection J. Immunol., November 15, 2001; 167(10): 5994 - 6001. [Abstract] [Full Text] [PDF]
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 S. W. Chensue Molecular Machinations: Chemokine Signals in Host-Pathogen Interactions Clin. Microbiol. Rev., October 1, 2001; 14(4): 821 - 835. [Abstract] [Full Text] [PDF]
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 A. Matsukawa, M. H. Kaplan, C. M. Hogaboam, N. W. Lukacs, and S. L. Kunkel Pivotal Role of Signal Transducer and Activator of Transcription (Stat)4 and Stat6 in the Innate Immune Response during Sepsis J. Exp. Med., March 12, 2001; 193(6): 679 - 688. [Abstract] [Full Text] [PDF]
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K. Blease, B. Mehrad, N. W. Lukacs, S. L. Kunkel, T. J. Standiford, and C. M. Hogaboam Antifungal and Airway Remodeling Roles for Murine Monocyte Chemoattractant Protein-1/CCL2 During Pulmonary Exposure to Asperigillus fumigatus Conidia J. Immunol., February 1, 2001; 166(3): 1832 - 1842. [Abstract] [Full Text] [PDF]
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M. L. Steinhauser, C. M. Hogaboam, A. Matsukawa, N. W. Lukacs, R. M. Strieter, and S. L. Kunkel Chemokine C10 Promotes Disease Resolution and Survival in an Experimental Model of Bacterial Sepsis Infect. Immun., November 1, 2000; 68(11): 6108 - 6114. [Abstract] [Full Text] [PDF]
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C. L. Bone-Larson, C. M. Hogaboam, M. L. Steinhauser, S. H. P. Oliveira, N. W. Lukacs, R. M. Strieter, and S. L. Kunkel Novel Protective Effects of Stem Cell Factor in a Murine Model of Acute Septic Peritonitis : Dependence on MCP-1 Am. J. Pathol., October 1, 2000; 157(4): 1177 - 1186. [Abstract] [Full Text] [PDF]
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B. Haribabu, M. W. Verghese, D. A. Steeber, D. D. Sellars, C. B. Bock, and R. Snyderman Targeted Disruption of the Leukotriene B4 Receptor in Mice Reveals Its Role in Inflammation and Platelet-activating Factor-induced Anaphylaxis J. Exp. Med., August 8, 2000; 192(3): 433 - 438. [Abstract] [Full Text] [PDF]
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A. Matsukawa, C. M. Hogaboam, N. W. Lukacs, P. M. Lincoln, H. L. Evanoff, and S. L. Kunkel Pivotal Role of the CC Chemokine, Macrophage-Derived Chemokine, in the Innate Immune Response J. Immunol., May 15, 2000; 164(10): 5362 - 5368. [Abstract] [Full Text] [PDF]
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 A. Turler, N. T. Schwarz, E. Turler, J. C. Kalff, and A. J. Bauer MCP-1 causes leukocyte recruitment and subsequently endotoxemic ileus in rat Am J Physiol Gastrointest Liver Physiol, January 1, 2002; 282(1): G145 - G155. [Abstract] [Full Text] [PDF]
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