Lymphatic function lymphangiogenic anti-lymphangiogenic

[patoco]

Lymphatic function is regulated by a coordinated expression of lymphangiogenic and anti-lymphangiogenic cytokines.

Am J Physiol Cell Physiol. 2011 Sep 21

Zampell J, Avraham T, Yoder N, Fort N, Yan A, Weitman ES, Mehrara BJ.

Source

Memorial Sloan-Kettering Cancer Center.

Abstract

Lymphangiogenic cytokines such as vascular endothelial growth factor-C (VEGF-C) are critically required for lymphatic regeneration; however, in some circumstances, lymphatic function is impaired despite normal or elevated levels of these cytokines. The recent identification of anti-lymphangiogenic molecules such as interferon-gamma (IFN-γ), transforming growth factor-beta 1, and endostatin has led us to hypothesize that impaired lymphatic function may represent a dysregulated balance in the expression of pro/anti-lymphangiogenic stimuli.

We observed that nude mice have significantly improved lymphatic function as compared with wild-type mice in a tail model of lymphedema. We show that gradients of lymphatic fluid stasis regulate the expression of lymphangiogenic cytokines (VEGF-A, VEGF-C, and hepatocyte growth factor) and that paradoxically, the expression of these molecules is increased in wild-type mice.

More importantly, we show that as a consequence of T-cell mediated inflammation, these same gradients also regulate expression patterns of anti-lymphangiogenic molecules corresponding temporally and spatially with impaired lymphatic function in wild-type mice. We show that neutralization of IFN-γ significantly increases inflammatory lymph node lymphangiogenesis independently of changes in VEGF-A or VEGF-C expression, suggesting that alterations in the balance of pro- and anti-lymphangiogenic cytokine expression can regulate lymphatic vessel formation.

In conclusion, we show that gradients of lymphatic fluid stasis regulate not only the expression of pro-lymphangiogenic cytokines but also potent suppressors of lymphangiogenesis as a consequence of T-cell inflammation and that modulation of the balance between these stimuli can regulate lymphatic function.

PMID: 21940662 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/21940662