Published online before print March 6, 2003, doi: 10.1161/01.RES.0000065621.69843.49
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© 2003 American Heart Association, Inc.
Integrative Physiology |
Interstitial Flow as a Guide for Lymphangiogenesis
From the Biomedical Engineering Department (K.C.B., M.A.S.) and the Chemical Engineering Department (M.A.S.), McCormick School of Engineering and Applied Sciences, Northwestern University, Evanston, Ill.
Correspondence to Melody A. Swartz, Chemical Engineering Department, McCormick School of Engineering and Applied Sciences, Northwestern University, 2145 Sheridan, Evanston, IL 60208-3107. E-mail m-swartz2{at}northwestern.edu
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.
Key Words: lymphatic capillary • interstitial fluid flow • vascular endothelial growth factor-C • lymphatic vessel hyaluronan receptor 1 • matrix metalloproteinases
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