title: Complementary adhesion molecules promote neutrophil-Kupffer cell interaction and the elimination of bacteria taken up by the liver.
abstract: Most bacteria that enter the bloodstream are taken up by the liver. Previously, we reported that such organisms are initially bound extracellularly and subsequently killed by immigrating neutrophils, not Kupffer cells as widely presumed in the literature. Rather, the principal functions of Kupffer cells demonstrated herein are to clear bacteria from the peripheral blood and to promote accumulation of bactericidal neutrophils at the principal site of microbial deposition in the liver, i.e., the Kupffer cell surface. In a mouse model of listeriosis, uptake of bacteria by the liver at 10 min postinfection i.v. was reduced from approximately 60% of the inoculum in normal mice to approximately 15% in mice rendered Kupffer cell deficient. Immunocytochemical analysis of liver sections derived from normal animals at 2 h postinfection revealed the massive immigration of neutrophils and their colocalization with Kupffer cells. Photomicrographs of the purified nonparenchymal liver cell population derived from these infected mice demonstrated listeriae inside neutrophils and neutrophils within Kupffer cells. Complementary adhesion molecules promoted the interaction between these two cell populations. Pretreatment of mice with mAbs specific for CD11b/CD18 (type 3 complement receptor) or its counter-receptor, CD54, inhibited the accumulation of neutrophils in the liver and the elimination of listeriae. Complement was not a factor; complement depletion affected neither the clearance of listeriae by Kupffer cells nor the antimicrobial activity expressed by infiltrating neutrophils.
authors.affiliation: Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. sgregory@lifespan.org
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Gregory
authors.forename: Leslie P
authors.initials: LP
authors.lastname: Cousens
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Ed A
authors.initials: EA
authors.lastname: Döpp
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Carlos
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Wing
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D003165:Complement System Proteins / Q000502:physiology; D005260:Female; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology*; D007700:Kinetics; D007728:Kupffer Cells / Q000166:cytology / Q000276:immunology*; D008089:Listeria monocytogenes / Q000302:isolation & purification; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008099:Liver / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D009195:Peroxidase / Q000378:metabolism; D018805:Sepsis / Q000276:immunology / Q000382:microbiology
chemical_list: D000906:Antibodies; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1; D003165:Complement System Proteins; D009195:Peroxidase