Intra-abdominal sepsis attenuates local inflammation-mediated increases in microvascular permeability at remote sites in mice in vivo.
BACKGROUND
Given that leukocyte delivery to remote sites is diminished in states of systemic inflammation, such as sepsis, and activated leukocytes may be responsible for endothelial injury leading to vascular leakage, we hypothesized that intra-abdominal sepsis would diminish microvascular leakage at remote sites by altering leukocyte-endothelial interactions.


METHODS
Using a murine intravital microscopy model, we examined leukocyte-endothelial interactions and vascular leakage at a peripheral site in the presence of local and/or systemic inflammation. Forty mice were randomized to 1 of 4 study groups: local infection (orchitis), systemic infection (intra-abdominal sepsis by cecal ligation and puncture), local and systemic infection, and control. Postcapillary venules of the cremaster muscle were examined by bright light and fluorescence intravital microscopy. Microvascular leakage was determined after intravenous administration of fluorescent albumin.


RESULTS
Systemic infection attenuated the increases in both leukocyte adherence and local infection-induced microvascular permeability. Neutrophil cell-surface expression of L-selectin, as determined by flow cytometry, diminished with both local and systemic infection, whereas expression of CD11b increased with systemic, but not local, infection.


CONCLUSIONS
These data suggest that systemic (intra-abdominal) sepsis diminishes local inflammation-mediated vascular leakage by attenuating leukocyte adherence.
Ferri
Lorenzo E
LE
Department of Surgery, McGill University Health Center, McGill University, Montreal, Quebec, Canada.
Pascual
Jose
J
Seely
Andrew J E
AJ
Giannias
Betty
B
Christou
Nicolas V
NV
D000005:Abdomen / Q000098:blood supply*; D000818:Animals; D002199:Capillary Permeability / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology; D036904:Leukocyte Rolling / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008833:Microcirculation / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D009920:Orchitis / Q000276:immunology* / Q000503:physiopathology; D018805:Sepsis / Q000276:immunology* / Q000503:physiopathology*