Editorial
LYMPHATIC RESEARCH AND BIOLOGY Volume 12, Number 3, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/lrb.2014.1231
Inflammatory Cytokines and the Lymphatic Endothelium Stanley G. Rockson, MD
T
he intimate relationship that links lymphatic function to the inflammatory response has recently been the subject of much intensive investigation and analysis.1,2 In the current issue of Lymphatic Research and Biology, we feature two original investigations that further explore the interrelationship of the lymphatic endothelium with inflammatory cytokines. Kawai et al. have chosen to explore the role of the lymphatic endothelium in regulating the permeability of the collecting vessel to hydrophilic substances.3 Positing that little is known about the mechanism through which the protein-concentrating effects of the lymphatic vasculature are modulated in states of inflammation, the authors chose to explore the function of cultured lymphatic endothelial cells in the size-dependent regulation permeability to hydrophilic substances. The effects of tumor necrosis factor (TNF)-a and interleukin (IL)-1b on both permeability and lymphatic endothelial cell morphology were examined by the investigators. Indeed, the authors were able to conclude that there is a physiological effect of the endothelial cell layer on permeability, and that the presence of the inflammatory cytokines significantly increases the permeability, ostensibly through Rho kinase activation and through ERK 1/2 phosphorylationmediated reorganization of F-actin in the lymphatic endothelial cell. In a parallel investigation, Kakei et al. have investigated the effect of inflammatory cytokines upon the intercellular junctions in human cultured lymphatic endothelia.4 The authors both characterized cell-cell junctions in the cultured endothelia and characterized the alterations in these charac-
teristics induced by exposure to the inflammatory cytokine, TNF-a. The cultured dermal lymphatic endothelial cells were immunostained for both tight junction and adherens junction markers. They describe heterogeneity in the staining, with identification of both continuous and discontinuous subtypes. Treatment with TNF-a induced both a reduction in transendothelial electrical resistance and a shift in the distribution of the cell-cell junctions, with induction of a predominance of the discontinuous morphology. Taken together, these two articles further elucidate the interesting and tightly controlled manner in which inflammatory cytokines interact with the biology of the lymphatic endothelium. References
1. Kim H, Kataru RP, Koh GY. Inflammation-associated lymphangiogenesis: A double-edged sword? J Clin Invest. 2014; 124:936–942. 2. Card CM, Yu SS, Swartz MA. Emerging roles of lymphatic endothelium in regulating adaptive immunity. J Clin Invest. 2014;124:943–952. 3. Kawai Y, Kaidoh M, Yokoyama Y, Ohhashi T. Pivotal roles of lymphatic endothelial cell layers in the permeability to hydrophilic substances through collecting lymph vessel walls: Effects of inflammatory cytokines. Lymphat Res Biol 2014;12:124–135. 4. Kakei Y, Akashi M, Shigeta T, Hasegawa T, Komori T. Alteration of cell–cell junctions in cultured human lymphatic endothelial cells with inflammatory cytokine stimulation. Lymphat Res Biol 2014;12:136–143.
Stanford University School of Medicine, Stanford, California.
123
LYMPHATIC RESEARCH AND BIOLOGY Volume 12, Number 3, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/lrb.2014.1231
Inflammatory Cytokines and the Lymphatic Endothelium Stanley G. Rockson, MD
T
he intimate relationship that links lymphatic function to the inflammatory response has recently been the subject of much intensive investigation and analysis.1,2 In the current issue of Lymphatic Research and Biology, we feature two original investigations that further explore the interrelationship of the lymphatic endothelium with inflammatory cytokines. Kawai et al. have chosen to explore the role of the lymphatic endothelium in regulating the permeability of the collecting vessel to hydrophilic substances.3 Positing that little is known about the mechanism through which the protein-concentrating effects of the lymphatic vasculature are modulated in states of inflammation, the authors chose to explore the function of cultured lymphatic endothelial cells in the size-dependent regulation permeability to hydrophilic substances. The effects of tumor necrosis factor (TNF)-a and interleukin (IL)-1b on both permeability and lymphatic endothelial cell morphology were examined by the investigators. Indeed, the authors were able to conclude that there is a physiological effect of the endothelial cell layer on permeability, and that the presence of the inflammatory cytokines significantly increases the permeability, ostensibly through Rho kinase activation and through ERK 1/2 phosphorylationmediated reorganization of F-actin in the lymphatic endothelial cell. In a parallel investigation, Kakei et al. have investigated the effect of inflammatory cytokines upon the intercellular junctions in human cultured lymphatic endothelia.4 The authors both characterized cell-cell junctions in the cultured endothelia and characterized the alterations in these charac-
teristics induced by exposure to the inflammatory cytokine, TNF-a. The cultured dermal lymphatic endothelial cells were immunostained for both tight junction and adherens junction markers. They describe heterogeneity in the staining, with identification of both continuous and discontinuous subtypes. Treatment with TNF-a induced both a reduction in transendothelial electrical resistance and a shift in the distribution of the cell-cell junctions, with induction of a predominance of the discontinuous morphology. Taken together, these two articles further elucidate the interesting and tightly controlled manner in which inflammatory cytokines interact with the biology of the lymphatic endothelium. References
1. Kim H, Kataru RP, Koh GY. Inflammation-associated lymphangiogenesis: A double-edged sword? J Clin Invest. 2014; 124:936–942. 2. Card CM, Yu SS, Swartz MA. Emerging roles of lymphatic endothelium in regulating adaptive immunity. J Clin Invest. 2014;124:943–952. 3. Kawai Y, Kaidoh M, Yokoyama Y, Ohhashi T. Pivotal roles of lymphatic endothelial cell layers in the permeability to hydrophilic substances through collecting lymph vessel walls: Effects of inflammatory cytokines. Lymphat Res Biol 2014;12:124–135. 4. Kakei Y, Akashi M, Shigeta T, Hasegawa T, Komori T. Alteration of cell–cell junctions in cultured human lymphatic endothelial cells with inflammatory cytokine stimulation. Lymphat Res Biol 2014;12:136–143.
Stanford University School of Medicine, Stanford, California.
123
