Response to Letter Regarding Article, “Biological Basis of Therapeutic Lymphangiogenesis”
We would like to thank Dr Toska for pointing out an inaccuracy pertaining to Figure 1 in our recent review article.1 Indeed, the figure reflects outdated textbook knowledge on the physiology of fluid exchange between the various compartments (arteries, capillaries, veins, lymphatic vessels, and the interstitium). According to current view, there is very little reabsorption in the venules simply because the tissue forces, which were not considered in the initial experiments by Landis and Pappenheimer, would prevent such a continuous process (reviewed in Levick and Michel2). Fresh lines of evidence suggest that the lymphatic vessels have a much more important role in the absorption of interstitial fluid in most tissues than previously thought (reviewed in Wiig3). In fact, it seems that most of the filtrate is cleared by the lymphatic vessels, which are the focus of our review. Most likely, fluid is transported by a pressure gradient in the interstitium to the next available lymphatic,2 which is not surprising, considering how aptly lymphatic vessels absorb fluid and proteins unselectively by bulk flow from the interstitial space (as opposed to the venules, which have considerably tighter walls and higher hydrostatic pressure).4,5 We have now corrected our online article accordingly, including Figure 1.
Camilla Norrmén, PhD
Tuomas Tammela, MD, PhD
Kari Alitalo, MD, PhD
Molecular/Cancer Biology Laboratory
Research Programs Unit
Institute for Molecular Medicine Finland
Helsinki University Hospital
Tatiana V. Petrova, PhD
Divison of Experimental Oncology and Department of
Multidisciplinary Oncology Center
University of Lausanne and University Hospital of Lausanne
Dr Alitalo is chairman of the Scientific Advisory Board of Circadian Ltd. and consultant to Laurantis Pharma Oy.
We thank Dr Helge Wiig and Dr Peter Mortimer for expert advice on addressing the recent understanding on interstitial fluid absorption.
- © 2011 American Heart Association, Inc.
- Norrmen C,
- Tammela T,
- Petrova TV,
- Alitalo K
- Levick JR,
- Michel CC
- Mortimer PS,
- Levick JR