Premium
Neuropilin 2 Deficiency Prolongs Skin Inflammation and Edema
Author(s) -
Bielenberg Diane Renee,
Mucka Patrick,
Levonyak Nicholas,
Geretti Elena,
Zwaans Bernadette M.M.,
Li Xiaoran,
Adini Irit,
Klagsbrun Michael,
Adam Rosalyn M
Publication year - 2016
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/fasebj.30.1_supplement.165.4
Subject(s) - lymphatic system , inflammation , vascular permeability , lymphatic endothelium , neuropilin 1 , medicine , edema , lymphatic vessel , neuropilin , endothelium , pathology , vascular endothelial growth factor c , vascular endothelial growth factor , cancer research , immunology , vascular endothelial growth factor a , metastasis , vegf receptors , cancer
The vasculature is involved in the progression and resolution of inflammation. Blood and lymphatic capillaries express vascular endothelial growth factor (VEGF) receptors that regulate fluid flow into and out of the interstitium. Neuropilin 2 (Nrp2), a unique receptor that binds VEGF‐A, VEGF‐C/D or semaphorin 3F (SEMA3F) ligands, is expressed by the endothelium during development but downregulated after birth. Mice lacking Nrp2 are viable into adulthood without signs of edema. Herein, we investigated the expression and function of Nrp2 in a model of acute inflammation. Immunoblotting and X‐gal staining of Nrp2 +/ LacZ mice showed increased Nrp2 or b‐galactosidase activity in the endothelium following delayed‐type hypersensitivity (DTH) reactions. Nrp2 −/− mice exhibited massive tissue swelling, prolonged lymphedema, and delayed resolution after DTH compared to wild‐type mice. Vascular permeability was two‐fold higher in inflamed blood vessels in Nrp2 ‐deficient mice compared to Nrp2 ‐intact littermates. Histological examination revealed a lack of superficial lymphatic capillaries in Nrp2 ‐mutant mice. Addition of exogenous SEMA3F protein inhibited VEGFA‐induced vascular permeability in wild‐type mice. In summary, Nrp2 deficiency increased blood vessel permeability and decreased lymphatic vessel drainage during inflammation. Taken together our data suggest that Nrp2 is upregulated in the endothelium to modulate inflammation‐induced tissue swelling and resolve post‐inflammatory edema. Support or Funding Information Vascular Biology Program, Boston Children's Hospital; NCI and NIDDK under award numbers CA118732, CA155728 (D.R.B.), CA037392 (M.K.), and DK65298 (R.M.A.).