title: Mannose-binding lectin augments the uptake of lipid A, Staphylococcus aureus, and Escherichia coli by Kupffer cells through increased cell surface expression of scavenger receptor A.
abstract: We investigated roles of scavenger receptor A (SR-A) and mannose-binding lectin (MBL) in the uptake of endotoxin and bacteria by Kupffer cells. When [3H]lipid A was injected into retro-orbital plexus of mice, significantly less accumulation of lipid A in the liver was observed in SR-A-deficient mice and wild-type mice coinjected with fucoidan or acetylated low-density lipoprotein, which are known ligands for SR-A. Isolated Kupffer cells were able to take up [3H]lipid A in a time-dependent manner. The amount of lipid A associated with nonadherent Kupffer cells derived from SR-A-deficient mice was reduced by approximately 80% when compared with wild-type cells, indicating an important role of SR-A in endotoxin uptake by Kupffer cells. The lipid A uptake by Kupffer cells was significantly enhanced in the presence of rMBL. Coincubation of fucoidan with [3H]lipid A significantly inhibited the basal and the MBL-stimulated uptake of lipid A by Kupffer cells. Preincubation of MBL with Kupffer cells also increased the uptake of lipid A. These results indicate that MBL augments the SR-A-mediated uptake of lipid A by Kupffer cells. Consistently, the exposure of MBL to Kupffer cells increased cell surface SR-A expression. The phagocytosis of Staphylococcus aureus and Escherichia coli by Kupffer cells was also enhanced by preincubation of MBL with the cells. In addition, MBL bound to lipid A, LPS, and S. aureus, and precipitated S. aureus. This study demonstrates important roles of SR-A and MBL in the uptake of endotoxin and bacteria by Kupffer cells.
authors.affiliation: Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Ono
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nishitani
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mitsuzawa
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Fujii
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukase
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kuroki
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004926:Escherichia coli / Q000378:metabolism*; D007728:Kupffer Cells / Q000378:metabolism*; D008050:Lipid A / Q000378:metabolism*; D037601:Mannose-Binding Lectin / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000502:physiology*; D013211:Staphylococcus aureus / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology
chemical_list: D008050:Lipid A; D037601:Mannose-Binding Lectin; D051117:Scavenger Receptors, Class A