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Nitric oxide mediates lymphatic vessel activation via soluble guanylate cyclase α1β1‐impact on inflammation
Author(s) -
Kajiya Kentaro,
Huggenberger Reto,
Drinnenberg Ines,
Ma Beijia,
Detmar Michael
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-8873com
Subject(s) - lymphangiogenesis , lymphatic system , inflammation , nitric oxide , lymphatic vessel , vascular endothelial growth factor c , lymphatic endothelium , microbiology and biotechnology , chemistry , cancer research , immune system , immunology , biology , medicine , vascular endothelial growth factor , vascular endothelial growth factor a , metastasis , cancer , organic chemistry , vegf receptors
The lymphatic vascular system regulates tissue fluid homeostasis and the afferent phase of the immune response, and it is also involved in tumor metastasis. There is increasing evidence that lymphatic vessels also mediate acute and chronic inflammation. However, the mechanisms and functional consequences of lymphangiogenesis under inflammatory conditions are largely unknown. Here, we show that lymphatic endothelial cells (LECs) specifically express the α1β1 isoform of soluble guanylate cyclase (sGC), that vascular endothelial growth factor‐A potently induces sGCα1β1, and that nitric oxide (NO) ‐induced LEC proliferation, migration, and cGMP production in LECs are specifically dependent on sGCα1β1. Moreover, the specific sGC inhibitor NS‐2028 completely prevents ultraviolet B‐irradiation‐induced lymphatic vessel enlargement, edema formation, and skin inflammation in vivo. These findings identify a crucial role of the NO/sGCα1β1/cGMP pathway in modulating lymphatic vessel function. The blockade of sGCα1β1 signaling might serve as a novel therapeutic strategyfor inhibiting lymphangiogenesis and inflammation, in addition to its effects on the blood vasculature.—Kajiya, K., Huggenberger, R., Drinnenberg, I., Ma, B., and Detmar, M. Nitric oxide mediates lymphatic vessel activation via soluble guanylate cyclase α1β1‐impact on inflammation. FASEB J. 22, 530–537 (2008)