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.
Keywords: Animals ; Antigens ; CD31/analysis ; Cell Movement ; Dextrans/diagnostic use ; Endothelial Growth Factors/analysis ; Endothelium ; Lymphatic/chemistry/cytology ; Endothelium ; Vascular/chemistry/cytology ; Fluorescein-5-isothiocyanate/*analogs & ; derivatives/diagnostic use ; Fluorescent Antibody Technique ; Glycoproteins/analysis ; Immunohistochemistry ; Lymph/*physiology ; Lymphatic System/*blood supply/chemistry/physiology ; Lymphography ; Matrix Metalloproteinases/metabolism ; Mice ; Mice ; Inbred BALB C ; Research Support ; Non-U.S. Gov't ; Research Support ; U.S. Gov't ; Non-P.H.S. ; Skin/blood supply/chemistry ; Tail/blood supply ; Vascular Endothelial Growth Factor C ; Vascular Endothelial Growth Factor Receptor-3/analysis
Record created on 2006-08-09, modified on 2016-08-08