Increased survival of P- and E-/P- selectin deficient mice during e. coli sepsis

The interaction between leukocytes and selectin molecules is crucial for the migration of neutrophils to sites of infection. Selectin deficiencies are severely detrimental for survival of mice with S. pneumonias infection. To characterize the role of the endothelial selectins during gram negative sepsis in vivo, E. coli (1-10 × 10⁸ cfu) was inoculated intraperitoneally in 8 week old mice with single E- (n=18), P- (n=12) and double E-/P- (n=18) selectin deficiencies or wild type (WT) (n=20). Mice were followed daily for 72 h for mortality and clearance of bacteremia. A second group (n=3-4 per group) was sacrificed at 6 h post inoculation to determine neutrophil migration to intraperitoneal sites of infection. Among all groups, a significantly higher 24-72 h survival was observed in the selectin deficient groups vs. WT (p=<.0001), particularly in the P-selectin (75% survival) (p=<.0001) and E-/P-selectin deficient mice (28% survival) (p=.05) vs. WT (16% survival). There were no significant differences among mutant vs. WT survivors in the bacterial load or clearance of bacteremia at 24-72 h post inoculation. No differences were noted in the number of neutrophils present in the peritoneal cavity, liver or spleen of mutants vs. WT mice at 6 h post inoculation, suggesting adequate migration of leukocytes to these sites of infection. We conclude that although single E-, P-, and double E-/P-selectin deficiencies do not significantly impair the migration of neutrophils to intraperitoneal sites of infection at 6 h after inoculation of E. coli, the absence of P-selectin or both E- and P-selectins and probably a reduction in the inflammatory reactions they mediate are beneficial for survival of mice with E. coli sepsis.