Interstitial flow as a guide for lymphangiogenesis.
The lymphatic system is important in tissue fluid balance regulation, immune cell trafficking, edema, and cancer metastasis, yet very little is known about the sequence of events that initiate and coordinate lymphangiogenesis. Here, we characterize the process of lymphatic regeneration by uniquely correlating interstitial fluid flow and lymphatic endothelial cell migration with lymphatic function. A new model of skin regeneration using a collagen implant in a mouse tail has been developed, and it shows that (1) interstitial fluid channels form before lymphatic endothelial cell organization and (2) lymphatic cell migration, vascular endothelial growth factor-C expression, and lymphatic capillary network organization are initiated primarily in the direction of lymph flow. These data suggest that interstitial fluid channeling precedes and may even direct lymphangiogenesis (in contrast to blood angiogenesis, in which fluid flow proceeds only after the vessel develops); thus, a novel and robust model is introduced for correlating molecular events with functionality in lymphangiogenesis.
Boardman
Kendrick C
KC
Chemical Engineering Department, McCormick School of Engineering and Applied Sciences, Northwestern University, 2145 Sheridan, Evanston, Ill 60208-3107, USA.
Swartz
Melody A
MA
D000818:Animals; D002465:Cell Movement; D003911:Dextrans; D016228:Endothelial Growth Factors / Q000032:analysis; D004729:Endothelium, Lymphatic / Q000737:chemistry / Q000166:cytology; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives*; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000032:analysis; D007150:Immunohistochemistry; D008196:Lymph / Q000502:physiology*; D008208:Lymphatic System / Q000098:blood supply* / Q000737:chemistry / Q000502:physiology; D008220:Lymphography; D020782:Matrix Metalloproteinases / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D012867:Skin / Q000098:blood supply / Q000737:chemistry; D013623:Tail / Q000098:blood supply; D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000032:analysis
D003911:Dextrans; D016228:Endothelial Growth Factors; D016650:Fluorescein-5-isothiocyanate; D006023:Glycoproteins; D020782:Matrix Metalloproteinases; D026901:Membrane Transport Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3; C492273:LYVE1 protein, mouse; C015219:fluorescein isothiocyanate dextran