Inflammation and Lymphedema Are Exacerbated and Prolonged by Neuropilin 2 Deficiency.
Am J Pathol
; 186(11): 2803-2812, 2016 11.
Article
en En
| MEDLINE
| ID: mdl-27751443
ABSTRACT
The vasculature influences the progression and resolution of tissue inflammation. Capillaries express vascular endothelial growth factor (VEGF) receptors, including neuropilins (NRPs), which regulate interstitial fluid flow. NRP2, a receptor of VEGFA and semaphorin (SEMA) 3F ligands, is expressed in the vascular and lymphatic endothelia. Previous studies have demonstrated that blocking VEGF receptor 2 attenuates VEGFA-induced vascular permeability. The inhibition of NRP2 was hypothesized to decrease vascular permeability as well. Unexpectedly, massive tissue swelling and edema were observed in Nrp2-/- mice compared with wild-type littermates after delayed-type hypersensitivity reactions. Vascular permeability was twofold greater in inflamed blood vessels in Nrp2-deficient mice compared to those in Nrp2-intact littermates. The addition of exogenous SEMA3F protein inhibited vascular permeability in Balb/cJ mice, suggesting that the loss of endogenous Sema3F activity in the Nrp2-deficient mice was responsible for the enhanced vessel leakage. Functional lymphatic capillaries are necessary for draining excess fluid after inflammation; however, Nrp2-mutant mice lacked superficial lymphatic capillaries, leading to 2.5-fold greater fluid retention and severe lymphedema after inflammation. In conclusion, Nrp2 deficiency increased blood vessel permeability and decreased lymphatic vessel drainage during inflammation, highlighting the importance of the NRP2/SEMA3F pathway in the modulation of tissue swelling and resolution of postinflammatory edema.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neuropilina-2
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Factor A de Crecimiento Endotelial Vascular
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Linfedema
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Proteínas de la Membrana
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Proteínas del Tejido Nervioso
Límite:
Animals
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Female
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Humans
Idioma:
En
Año:
2016
Tipo del documento:
Article