title: Mice genetically lacking endothelial selectins are resistant to the lethality in septic peritonitis.
abstract: Leukocyte interactions with vascular endothelium are an initial step for leukocyte entry into infectious foci where endothelial selectins may play a key role. Infiltrating leukocyte is essential for bacterial clearance, suggesting that endothelial selectins would be important in host defense against microorganisms. To address this, E-, P-, and E/P-selectin-deficient mice (E(-/-), P(-/-), E/P(-/-)) and wild-type (WT) mice underwent cecal ligation and puncture (CLP). Neither leukocyte infiltration nor bacterial load in the peritoneum was altered in E(-/-), P(-/-), and E/P(-/-) mice compared to WT mice. However, E(-/-), P(-/-), and E/P(-/-) mice were resistant to the lethality induced by CLP. At the mechanistic level, E(-/-), P(-/-), and E/P(-/-) mice did not develop renal dysfunction, a possible cause of death during sepsis. The serum level of interleukin-13 in E(-/-), P(-/-), and E/P(-/-) mice that had undergone CLP was higher than that in WT mice, whereas levels of macrophage inflammatory protein-2, KC in serum, and KC in kidney were lower than those in WT mice. These experiments demonstrate that endothelial selectin-mediated leukocyte rolling is not required for leukocyte entry in septic peritonitis and that endothelial selectins may affect mice survival during sepsis by influencing the cytokine profiles.
authors.affiliation: Department of Pathology, Kumamoto University School of Medicine, Kumamoto, 860-0811, Japan. matsu@kaiju.medic.kumamoto-u.ac.jp
authors.forename: Akihiro
authors.initials: A
authors.lastname: Matsukawa
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Lukacs
authors.forename: Cory M
authors.initials: CM
authors.lastname: Hogaboam
authors.forename: Randall N
authors.initials: RN
authors.lastname: Knibbs
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Bullard
authors.forename: Steven L
authors.initials: SL
authors.lastname: Kunkel
authors.forename: Lloyd M
authors.initials: LM
authors.lastname: Stoolman
mesh_terms: D000818:Animals; D001769:Blood / Q000382:microbiology; D002432:Cecum / Q000601:surgery; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010533:Peritoneal Lavage; D010538:Peritonitis / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D009195:Peroxidase / Q000378:metabolism; D019087:Selectins / Q000235:genetics* / Q000502:physiology*; D018805:Sepsis / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D015996:Survival Rate
chemical_list: D016207:Cytokines; D019087:Selectins; D009195:Peroxidase