title: Leukotriene B4 receptor (BLT-1) modulates neutrophil influx into the peritoneum but not the lung and liver during surgically induced bacterial peritonitis in mice.
abstract: 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.
authors.affiliation: Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Scott
authors.forename: William G
authors.initials: WG
authors.lastname: Cheadle
authors.forename: J Jason
authors.initials: JJ
authors.lastname: Hoth
authors.forename: James C
authors.initials: JC
authors.lastname: Peyton
authors.forename: Krishnaprasad
authors.initials: K
authors.lastname: Subbarao
authors.forename: Wen-Hai
authors.initials: WH
authors.lastname: Shao
authors.forename: Bodduluri
authors.initials: B
authors.lastname: Haribabu
mesh_terms: D000818:Animals; D001419:Bacteria / Q000302:isolation & purification; D001424:Bacterial Infections / Q000473:pathology; D054426:Chemokine CXCL2; D018925:Chemokines / Q000032:analysis; D002634:Chemotaxis, Leukocyte; D007958:Leukocyte Count; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D018375:Neutrophil Activation; D009504:Neutrophils / Q000166:cytology / Q000502:physiology*; D010537:Peritoneum / Q000473:pathology; D010538:Peritonitis / Q000382:microbiology / Q000473:pathology*; D009195:Peroxidase / Q000032:analysis; D018102:Receptors, Leukotriene B4 / Q000032:analysis / Q000235:genetics / Q000502:physiology*
chemical_list: D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D018102:Receptors, Leukotriene B4; D009195:Peroxidase