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Article

The Kinetics of Lymphatic Dysfunction and Leukocyte Expansion in the Draining Lymph Node during LTB4 Antagonism in a Mouse Model of Lymphedema

1
Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA
2
George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
3
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
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Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA
5
VA Palo Alto Health Care System, Palo Alto, CA 94304, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Joseph M. Rutkowski and Rachelle Crescenzi
Int. J. Mol. Sci. 2021, 22(9), 4455; https://doi.org/10.3390/ijms22094455
Received: 2 March 2021 / Revised: 20 April 2021 / Accepted: 22 April 2021 / Published: 24 April 2021
(This article belongs to the Special Issue Current Mechanistic Understandings of Lymphedema and Lipedema)
The mechanisms of lymphedema development are not well understood, but emerging evidence highlights the crucial role the immune system plays in driving its progression. It is well known that lymphatic function deteriorates as lymphedema progresses; however, the connection between this progressive loss of function and the immune-driven changes that characterize the disease has not been well established. In this study, we assess changes in leukocyte populations in lymph nodes within the lymphatic drainage basin of the tissue injury site (draining lymph nodes, dLNs) using a mouse tail model of lymphedema in which a pair of draining collecting vessels are left intact. We additionally quantify lymphatic pump function using established near infrared (NIR) lymphatic imaging methods and lymph-draining nanoparticles (NPs) synthesized and employed by our team for lymphatic tissue drug delivery applications to measure lymphatic transport to and resulting NP accumulation within dLNs associated with swelling following surgery. When applied to assess the effects of the anti-inflammatory drug bestatin, which has been previously shown to be a possible treatment for lymphedema, we find lymph-draining NP accumulation within dLNs and lymphatic function to increase as lymphedema progresses, but no significant effect on leukocyte populations in dLNs or tail swelling. These results suggest that ameliorating this loss of lymphatic function is not sufficient to reverse swelling in this surgically induced disease model that better recapitulates the extent of lymphatic injury seen in human lymphedema. It also suggests that loss of lymphatic function during lymphedema may be driven by immune-mediated mechanisms coordinated in dLNs. Our work indicates that addressing both lymphatic vessel dysfunction and immune cell expansion within dLNs may be required to prevent or reverse lymphedema when partial lymphatic function is sustained. View Full-Text
Keywords: lymphedema; leukocyte; lymphatic; near-infrared imaging; lymph node; leukotriene B4; bestatin; immune response lymphedema; leukocyte; lymphatic; near-infrared imaging; lymph node; leukotriene B4; bestatin; immune response
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MDPI and ACS Style

Cribb, M.T.; Sestito, L.F.; Rockson, S.G.; Nicolls, M.R.; Thomas, S.N.; Dixon, J.B. The Kinetics of Lymphatic Dysfunction and Leukocyte Expansion in the Draining Lymph Node during LTB4 Antagonism in a Mouse Model of Lymphedema. Int. J. Mol. Sci. 2021, 22, 4455. https://doi.org/10.3390/ijms22094455

AMA Style

Cribb MT, Sestito LF, Rockson SG, Nicolls MR, Thomas SN, Dixon JB. The Kinetics of Lymphatic Dysfunction and Leukocyte Expansion in the Draining Lymph Node during LTB4 Antagonism in a Mouse Model of Lymphedema. International Journal of Molecular Sciences. 2021; 22(9):4455. https://doi.org/10.3390/ijms22094455

Chicago/Turabian Style

Cribb, Matthew T., Lauren F. Sestito, Stanley G. Rockson, Mark R. Nicolls, Susan N. Thomas, and J. Brandon Dixon. 2021. "The Kinetics of Lymphatic Dysfunction and Leukocyte Expansion in the Draining Lymph Node during LTB4 Antagonism in a Mouse Model of Lymphedema" International Journal of Molecular Sciences 22, no. 9: 4455. https://doi.org/10.3390/ijms22094455

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