Neutrophil serine protease 4 is required for mast cell-dependent vascular leakage.
Commun Biol
; 3(1): 687, 2020 11 19.
Article
en En
| MEDLINE
| ID: mdl-33214666
ABSTRACT
Vascular leakage, or edema, is a serious complication of acute allergic reactions. Vascular leakage is triggered by the release of histamine and serotonin from granules within tissue-resident mast cells. Here, we show that expression of Neutrophil Serine Protease 4 (NSP4) during the early stages of mast cell development regulates mast cell-mediated vascular leakage. In myeloid precursors, the granulocyte-macrophage progenitors (GMPs), loss of NSP4 results in the decrease of cellular levels of histamine, serotonin and heparin/heparan sulfate. Mast cells that are derived from NSP4-deficient GMPs have abnormal secretory granule morphology and a sustained reduction in histamine and serotonin levels. Consequently, in passive cutaneous anaphylaxis and acute arthritis models, mast cell-mediated vascular leakage in the skin and joints is substantially reduced in NSP4-deficient mice. Our findings reveal that NSP4 is required for the proper storage of vasoactive amines in mast cell granules, which impacts mast cell-dependent vascular leakage in mouse models of immune complex-mediated diseases.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Serina Proteasas
/
Mastocitos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Commun Biol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos