TY - JOUR
T1 - Mice genetically lacking endothelial selectins are resistant to the lethality in septic peritonitis
AU - Matsukawa, Akihiro
AU - Lukacs, Nicholas W.
AU - Hogaboam, Cory M.
AU - Knibbs, Randall N.
AU - Bullard, Daniel C.
AU - Kunkel, Steven L.
AU - Stoolman, Lloyd M.
N1 - Funding Information:
The authors thank Ms. Pamela M. Lincoln and Holly L. Evanoff for their excellent technical assistance. This work was supported in part by National Institutes of Health Grants P50HL60289 and HL31237.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Cytokine balance
KW - Endothelial selectin
KW - Leukocyte infiltration
KW - Renal dysfunction
KW - Sepsis
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U2 - 10.1006/exmp.2001.2416
DO - 10.1006/exmp.2001.2416
M3 - Article
C2 - 11784125
AN - SCOPUS:0036349577
SN - 0014-4800
VL - 72
SP - 68
EP - 76
JO - Experimental and Molecular Pathology
JF - Experimental and Molecular Pathology
IS - 1
ER -