title: Effect of deletion of cIAP2 on intestinal microcirculation in mouse endotoxemia and polybacterial sepsis.
abstract: Deletion of the cellular inhibitor of apoptosis protein 2 (cIAP2) is capable of rendering lipopolysaccharide (LPS)-activated macrophages highly susceptible to apoptotic triggers, thereby quickly eliminating the resident macrophage population soon after the initiation of a systemic inflammatory response. The aim of our study was to evaluate the impact of cIAP2 deletion on leukocyte recruitment and capillary perfusion in experimental endotoxemia and polybacterial sepsis using intravital microscopy of the intestinal microcirculation, which is crucial in the pathogenesis of septic multiple organ failure. We studied six groups of animals: wild-type (WT) control mice, cIAP2 knockout mice, endotoxemic WT mice (5 mg/kg LPS), endotoxemic cIAP2 knockouts (5 or 50 mg/kg LPS, respectively), and WT as well as knockout mice with polybacterial sepsis (colon ascendens stent peritonitis [CASP]). Intravital microscopy of the intestinal microcirculation was performed after 1 h of endotoxemia or 12 h of CASP-induced sepsis, respectively. Intestinal microvascular blood flow was measured using laser Doppler flowmetry. After 1 h of endotoxemia (5 mg/kg LPS), we observed a significant increase of leukocyte adhesion in intestinal submucosal venules of WT mice in comparison with control animals. The cIAP2 knockout mice showed a significant reduction in leukocyte recruitment within the intestinal submucosal microvasculature after 5 or 50 mg/kg LPS challenge, respectively. Lipopolysaccharide-induced decrease in intestinal microvascular blood flow was not affected by cIAP2 inhibition. In CASP-induced sepsis, cIAP2 deletion had no effect on intestinal leukocyte recruitment. Deletion of cIAP2 resulted in reduced microvascular leukocyte recruitment within the intestinal microcirculation in endotoxemia but not in polybacterial sepsis.
authors.affiliation: *Departments of Anesthesia, †Pharmacology, and ‡Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada; §Department of Anesthesia and Intensive Care Medicine, Ernst-Moritz-Arndt-University, Greifswald, Germany; **Department of Anesthesiology and Intensive Care Medicine, Charles University Prague, Faculty of Medicine Hradec Kralove, Hradec Kralove, Czech Republic; and ∥Departments of Surgery, and ¶Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Lehmann
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.forename: Lea
authors.initials: L
authors.lastname: Schuster
authors.forename: Friederike
authors.initials: F
authors.lastname: Götz
authors.forename: Annette
authors.initials: A
authors.lastname: Wegner
authors.forename: Vladimir
authors.initials: V
authors.lastname: Cerny
authors.forename: Dragan
authors.initials: D
authors.lastname: Pavlovic
authors.forename: George S
authors.initials: GS
authors.lastname: Robertson
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D007422:Intestines / Q000098:blood supply; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008833:Microcirculation / Q000235:genetics / Q000502:physiology; D018805:Sepsis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: D051034:Inhibitor of Apoptosis Proteins