Inflammation-associated lymphangiogenesis: a double-edged sword?
Honsoul Kim, … , Raghu P. Kataru, Gou Young Koh
Honsoul Kim, … , Raghu P. Kataru, Gou Young Koh
Published March 3, 2014
Citation Information: J Clin Invest. 2014;124(3):936-942. https://doi.org/10.1172/JCI71607.
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Review Series

Inflammation-associated lymphangiogenesis: a double-edged sword?

Abstract

Lymphangiogenesis and lymphatic vessel remodeling are complex biological processes frequently observed during inflammation. Accumulating evidence indicates that inflammation-associated lymphangiogenesis (IAL) is not merely an endpoint event, but actually a phenomenon actively involved in the pathophysiology of various inflammatory disorders. The VEGF-C/VEGFR-3 and VEGF-A/VEGF-R2 signaling pathways are two of the best-studied pathways in IAL. Methods targeting these molecules, such as prolymphangiogenic or antilymphatic treatments, were found to be beneficial in various preclinical and/or clinical studies. This Review focuses on the most recent achievements in the fields of lymphatic biology relevant to inflammatory conditions. Additionally, preclinical and clinical therapies that modulate IAL are summarized.

Authors

Honsoul Kim, Raghu P. Kataru, Gou Young Koh

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Figure 2

In LNs, the balance between the prolymphangiogenic factors (VEGF-A, VEGF-C, VEGF-D) and antilymphangiogenic factors (IFN-γ) influences the actual response of lymphatic vessels to inflammatory stimuli; accordingly, lymphatic vessels either grow or regress.

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In LNs, the balance between the prolymphangiogenic factors (VEGF-A, VEGF...
During the acute stage of inflammation, the prolymphangiogenic factors usually dominate, in which case the final outcome is growth of the lymphatic vessels. As inflammation resolves, the antilymphangiogenic effect increases. Other regulators with either prolymphangiogenic or antilymphangiogenic effects have been reported; however, further studies are necessary before their role can be generalized. The coordination between stromal cells, immune cells, and interstitial flow seem to be other factors that affect the spatiotemporal regulation of IAL.