| First Author | AhYoung AP | Year | 2020 |
| Journal | Commun Biol | Volume | 3 |
| Issue | 1 | Pages | 687 |
| PubMed ID | 33214666 | Mgi Jnum | J:301479 |
| Mgi Id | MGI:6505400 | Doi | 10.1038/s42003-020-01407-0 |
| Citation | AhYoung AP, et al. (2020) Neutrophil serine protease 4 is required for mast cell-dependent vascular leakage. Commun Biol 3(1):687 |
| abstractText | 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. |
