Mice genetically lacking endothelial selectins are resistant to the lethality in septic peritonitis.
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.
Matsukawa
Akihiro
A
Department of Pathology, Kumamoto University School of Medicine, Kumamoto, 860-0811, Japan. matsu@kaiju.medic.kumamoto-u.ac.jp
Lukacs
Nicholas W
NW
Hogaboam
Cory M
CM
Knibbs
Randall N
RN
Bullard
Daniel C
DC
Kunkel
Steven L
SL
Stoolman
Lloyd M
LM
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
D016207:Cytokines; D019087:Selectins; D009195:Peroxidase