title: Pivotal roles of lymphatic endothelial cell layers in the permeability to hydrophilic substances through collecting lymph vessel walls: effects of inflammatory cytokines.
abstract: To address physiological and pathophysiological meanings of condensing effect of albumin in lymph through collecting lymph vessel walls, we established human lymphatic endothelial cells (LEC) and evaluated the size-dependent regulation of the permeability of such layers to hydrophilic substances. We also investigated the effects of tumor necrosis factor (TNF)-α or interleukin (IL)-1β on the permeability and on the morphology of human LEC. Significant amounts of 4 kDa dextran, but not 12 or 66 kDa dextran, passed through the layers. TNF-α or IL-1β induced significant increases in the permeability to 4 and 12 kDa dextrans. TNF-α or IL-1β also produced significant redistribution of the cytoskeletal F-actin in the LEC, which resulted in changes in their shape. Pretreatment with Y-27632, a Rho kinase inhibitor, or PD98059, an extracellular signal-regulated kinase (ERK) phosphorylation inhibitor, significantly abolished the TNF-α- or IL-1β-induced increases in the permeability of the layers to 4 and 12 kDa dextrans. Y-27632 and PD98059 significantly inhibited the changes in the F-actin distribution of the LEC produced by TNF-α or IL-1β. TNF-α or IL-1β caused significant increases in ERK 1/2 phosphorylation in the LEC, which were significantly inhibited by Y-27632 or PD98059. These findings suggest that the human LEC layer plays key roles in the transport of hydrophilic substances through collecting lymph vessel walls and that TNF-α or IL-1β significantly increases the permeability of the layers to 4 and 12 kDa dextrans via Rho kinase activation and the ERK 1/2 phosphorylation-mediated reorganization of F-actin in the LEC.
authors.affiliation: Department of Physiology, Shinshu University School of Medicine , Matsumoto. Japan .
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kawai
authors.forename: Maki
authors.initials: M
authors.lastname: Kaidoh
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Toshio
authors.initials: T
authors.lastname: Ohhashi
mesh_terms: D000577:Amides / Q000494:pharmacology; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D042601:Lymphatic Vessels / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology
chemical_list: D000577:Amides; D016207:Cytokines; D005419:Flavonoids; D018836:Inflammation Mediators; D011725:Pyridines; C108830:Y 27632; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one