title: Hepatic killing but not clearance of systemically circulating bacteria is dependent upon peripheral leukocytes via Mac-1 (CD11b/CD18).
abstract: The hepatic reticuloendothelial system (RES) is the primary mechanism for removing circulating bacteria from the systemic circulation. While Kupffer cells are important for this process, leukocytes appear to play a significant role as well. Hepatic leukocyte accumulation following ischemia/reperfusion or cytokine stimulation is well documented, but its contribution to phagocytic killing by the hepatic RES is not fully understood. We evaluated the role of leukocytes in general, and leukocyte-endothelial adhesion in particular, in hepatic RES function. This was done by inducing confirmed leukopenia with cyclophosphamide or by blocking leukocyte-endothelial adhesion molecules with specific blocking antibodies. Hepatic phagocytic clearance (HPC) and hepatic phagocytic killing (HKE) of systemically intravenously injected E. coli were assayed and quantitated by a validated dual isotope label technique. HPC among the various experimental groups and respective controls varied only slightly, with no statistically significant differences observed. Leukopenia or CD11b blockade each significantly decreased the HKE relative to the controls. Antibody blockade of certain other adhesion molecules had no significant effect on HKE (or HPC). The role of leukocytes in killing systemically circulating bacteria is an integral component of hepatic RES function. This capability of the leukocyte appears to be dependent, in part, on the adhesion molecule, Mac-1.
authors.affiliation: Department of Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
authors.forename: Mathew L
authors.initials: ML
authors.lastname: Brengman
authors.forename: Dajie
authors.initials: D
authors.lastname: Wang
authors.forename: Kirsten B
authors.initials: KB
authors.lastname: Wilkins
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Arai
authors.forename: Eugene P
authors.initials: EP
authors.lastname: Ceppa
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Klein
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Bulkley
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000097:blood; D039481:CD11b Antigen / Q000097:blood; D004926:Escherichia coli / Q000502:physiology*; D004927:Escherichia coli Infections / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D007728:Kupffer Cells / Q000382:microbiology*; D007970:Leukopenia / Q000097:blood / Q000276:immunology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D015703:Antigens, CD; D039481:CD11b Antigen; D018799:Intercellular Adhesion Molecule-1