Role of CD11b+ macrophages in intraperitoneal lipopolysaccharide-induced aberrant lymphangiogenesis and lymphatic function in the diaphragm.
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.
Kim
Kyung Eun
KE
National Research Laboratory of Vascular Biology and Department of Biological Sciences and Graduate School of Nanoscience and Technology (World Class University), Korea.
Koh
Young-Jun
YJ
Jeon
Bong-Hyun
BH
Jang
Cholsoon
C
Han
Jinah
J
Kataru
Raghu P
RP
Schwendener
Reto A
RA
Kim
Jin-Man
JM
Koh
Gou Young
GY
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
D039481:CD11b Antigen; D008024:Ligands; D008070:Lipopolysaccharides; D008081:Liposomes; D004002:Clodronic Acid; D040321:Vascular Endothelial Growth Factor Receptor-3