title: Role of CD11b+ macrophages in intraperitoneal lipopolysaccharide-induced aberrant lymphangiogenesis and lymphatic function in the diaphragm.
abstract: Lymphatic vessels in the diaphragm are essential for draining peritoneal fluid, but little is known about their pathological changes during inflammation. Here we characterized diaphragmatic lymphatic vessels in a peritonitis model generated by daily i.p. administration of lipopolysaccharide (LPS) in mice. Intraperitoneal LPS increased lymphatic density, branching, sprouts, connections, and network formation in the diaphragm in time- and dose-dependent manners. These changes were reversible on discontinuation of LPS administration. The LPS-induced lymphatic density and remodeling occur mainly through proliferation of lymphatic endothelial cells. CD11b+ macrophages were massively accumulated and closely associated with the lymphatic vessels changed by i.p. LPS. Both RT-PCR assays and experiments with vascular endothelial growth factor-C/D blockade and macrophage-depletion indicated that the CD11b+ macrophage-derived lymphangiogenic factors vascular endothelial growth factor-C/D could be major mediators of LPS-induced lymphangiogenesis and lymphatic remodeling through paracrine activity. Functional assays with India ink and fluorescein isothiocyanate-microspheres indicated that impaired peritoneal fluid drainage in diaphragm of LPS-induced peritonitis mice was due to inflammatory fibrosis and massive attachment of CD11b+ macrophages on the peritoneal side of the diaphragmatic lymphatic vessels. These findings reveal that CD11b+ macrophages play an important role in i.p. LPS-induced aberrant lymphangiogenesis and lymphatic dysfunction in the diaphragm.
authors.affiliation: National Research Laboratory of Vascular Biology and Department of Biological Sciences and Graduate School of Nanoscience and Technology (World Class University), Korea.
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Kim
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Koh
authors.forename: Bong-Hyun
authors.initials: BH
authors.lastname: Jeon
authors.forename: Cholsoon
authors.initials: C
authors.lastname: Jang
authors.forename: Jinah
authors.initials: J
authors.lastname: Han
authors.forename: Raghu P
authors.initials: RP
authors.lastname: Kataru
authors.forename: Reto A
authors.initials: RA
authors.lastname: Schwendener
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Koh
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004002:Clodronic Acid / Q000494:pharmacology; D003964:Diaphragm / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D007274:Injections, Intraperitoneal; D008024:Ligands; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000494:pharmacology*; D008081:Liposomes; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D042583:Lymphangiogenesis / Q000187:drug effects*; D042601:Lymphatic Vessels / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010538:Peritonitis / Q000139:chemically induced / Q000503:physiopathology; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D008024:Ligands; D008070:Lipopolysaccharides; D008081:Liposomes; D004002:Clodronic Acid; D040321:Vascular Endothelial Growth Factor Receptor-3