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Clinical and Diagnostic Laboratory Immunology, September 2004, p. 936-941, Vol. 11, No. 5
1071-412X/04/$08.00+0     DOI: 10.1128/CDLI.11.5.936-941.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Leukotriene B₄ Receptor (BLT-1) Modulates Neutrophil Influx into the Peritoneum but Not the Lung and Liver during Surgically Induced Bacterial Peritonitis in Mice

Melanie J. Scott,¹ William G. Cheadle,^2,3,4* J. Jason Hoth,⁵ James C. Peyton,⁴ Krishnaprasad Subbarao,³ Wen-Hai Shao,³ and Bodduluri Haribabu^3,6

Departments of Surgery,² Microbiology and Immunology, University of Louisville School of Medicine,³ Veterans Affairs Medical Center,⁴ James Graham Brown Cancer Center, Louisville, Kentucky,⁶ Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania,¹ Department of Surgery, Wake Forest University, Winston-Salem, North Carolina⁵

Received 6 April 2004/ Returned for modification 22 May 2004/ Accepted 19 June 2004

Leukotriene B₄ (LTB₄) is a rapidly synthesized, early neutrophil chemoattractant that signals via its cell surface receptor, BLT-1, to attract and activate neutrophils during peritonitis. BLT-1-deficient (BLT-1^–/–) mice were used to determine the effects of LTB₄ on neutrophil migration and activation, bacterial levels, and survival after cecal ligation and puncture (CLP). Male BLT-1^–/– or wild-type (WT) BALB/c mice underwent CLP. Tissues were harvested for determination of levels of bacteria, myeloperoxidase (MPO), LTB₄, macrophage inflammatory protein 2 (MIP-2), and neutrophil (polymorphonuclear leukocyte [PMN]) numbers at 4 and 18 h after CLP. PMN activation was determined by an assessment of phagocytosis ability and CD11b expression. Survival was also determined. BLT-1^–/– mice had decreased numbers of PMNs in the peritoneum at both 4 and 18 h after CLP but increased numbers of PMNs in the blood at 18 h compared with WT mice. Liver and lung MPO levels were significantly higher in BLT-1^–/– mice at both 4 and 18 h after CLP, with increased bacterial levels in the blood, the liver, and peritoneal fluid at 4 h. Bacterial levels remained higher in peritoneal fluid at 18 h, but blood and liver bacterial levels at 18 h were not different from levels at 4 h. PMN phagocytosis and CD11b levels were decreased in BLT-1^–/– mice. LTB₄ levels were similar between the groups before and after CLP, but MIP-2 levels were decreased both locally and systemically in BLT-1^–/– mice. Survival was significantly improved in BLT-1^–/– mice (71%) compared with WT mice (14%) at 48 h post-CLP. Thus, LTB₄ modulates neutrophil migration into the mouse peritoneum, but not the lung or liver, after CLP. Despite higher bacterial and PMN levels at remote sites, there was increased survival in BLT-1^–/– mice compared to WT mice. Decreased PMN activation may result in less remote organ dysfunction and improved survival.

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* Corresponding author. Mailing address: Department of Surgery, University of Louisville, Louisville, KY 40292. Phone: (502) 852-6230. Fax: (502) 852-8915. E-mail: wg.cheadle{at}louisville.edu.

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Clinical and Diagnostic Laboratory Immunology, September 2004, p. 936-941, Vol. 11, No. 5
1071-412X/04/$08.00+0     DOI: 10.1128/CDLI.11.5.936-941.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.