title: Neutrophil-induced liver cell injury in endotoxin shock is a CD11b/CD18-dependent mechanism.
abstract: To investigate the role of neutrophils (PMNs) and PMN-dependent adhesion molecules in the pathogenesis of liver injury in a model of endotoxin shock, male ICR mice received a dose of 700 mg/kg galactosamine and 100 micrograms/kg Salmonella abortus equi endotoxin. PMNs accumulated continuously in the liver, reaching values of 446 +/- 71 PMNs/50 high-power fields at 9 h (basal value 18 +/- 7). Plasma alanine aminotransferase activities as index of parenchymal cell injury did not change up to 5 h posttreatment (basal value 35 +/- 5 U/l) but increased to 1,950 +/- 460 U/l at 9 h. The formation of glutathione disulfide (GSSG) in plasma as an index of an extracellular oxidant stress also increased only at 9 h. Pretreatment of animals with monoclonal antibodies against the CD11b and CD18 subunits of the CD11/CD18 integrin family on the surface of the PMN reduced the number of PMNs in the liver by 50% and significantly attenuated liver injury and GSSG formation. An anti-CD11a and a nonbinding control antibody were ineffective. It is concluded that PMNs are actively involved in the pathogenesis of galactosamine and endotoxin shock and that at least in part the accumulation of PMNs, the subsequent oxidant stress, and the tissue injury in this model of experimental hepatitis are CD11b/CD18 (Mac-1) dependent.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
authors.forename: H
authors.initials: H
authors.lastname: Jaeschke
authors.forename: A
authors.initials: A
authors.lastname: Farhood
authors.forename: C W
authors.initials: CW
authors.lastname: Smith
mesh_terms: D000818:Animals; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009504:Neutrophils / Q000502:physiology*; D016897:Respiratory Burst; D012772:Shock, Septic / Q000276:immunology / Q000473:pathology*
chemical_list: D016177:Macrophage-1 Antigen