title: Adhesion molecules involved in neutrophil recruitment during sepsis-induced acute kidney injury.
abstract: Acute kidney injury (AKI) is a common complication in critically ill patients and is associated with high mortality. Recruitment of neutrophils is a hallmark in the pathogenesis of AKI. Although ischemia-reperfusion injury (IRI) is a frequently used research model of AKI, the clinical relevance of IRI-induced AKI is limited. Epidemiologically, sepsis is the prevailing cause of kidney injury. However, it is still unknown whether these distinct entities of AKI share the same pathophysiological mechanisms. This study was initiated to investigate the molecular mechanisms of neutrophil recruitment into the kidney in a murine model of sepsis-induced AKI. By using a flow cytometry-based method, we show that the two β2-integrins Mac-1 and LFA-1 as well as E-selectin and P-selectin are involved in neutrophil recruitment into the kidney after induction of sepsis. The molecular mechanisms of neutrophil recruitment were further investigated using intravital microscopy, demonstrating that blocking one of these four molecules reduces the number of adherent leukocytes. This was accompanied by a renal upregulation of E-selectin, P-selectin and ICAM-1 (the counter-receptor of β2-integrins on endothelial cells) after sepsis induction. We conclude that blocking P-selectin, E-selectin, Mac-1 or LFA-1 protects mice from sepsis-induced AKI.
authors.affiliation: Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass., USA.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Herter
authors.forename: Jan
authors.initials: J
authors.lastname: Rossaint
authors.forename: Tilmann
authors.initials: T
authors.lastname: Spieker
authors.forename: Alexander
authors.initials: A
authors.lastname: Zarbock
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy / Q000276:immunology*; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology*; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D019040:E-Selectin; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1