2017年11月
Mast cell hyperactivity underpins the development of oxygen-induced retinopathy
JOURNAL OF CLINICAL INVESTIGATION
- 巻
- 127
- 号
- 11
- 開始ページ
- 3987
- 終了ページ
- 4000
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1172/JCI89893
- 出版者・発行元
- AMER SOC CLINICAL INVESTIGATION INC
Mast cells are classically thought to play an important role in protection against helminth infections and in the induction of allergic diseases; however, recent studies indicate that these cells also contribute to neovascularization, which is critical for tissue remodeling, chronic inflammation, and carcinogenesis. Here, we demonstrate that mast cells are essential for sprouting angiogenesis in a murine model of oxygen-induced retinopathy (OIR). Although mouse strains lacking mast cells did not exhibit retinal neovascularization following hypoxia, these mice developed OIR following infusion of mast cells or after injection of mast cell tryptase (MCT). Relative hypoxia stimulated mast cell degranulation via transient receptor potential ankyrin 1. Subsequent surges in MCT stimulated retinal endothelial cells to produce monocyte chemotactic protein-1 (MCP1) and angiogenic factors, leading to sprouting angiogenesis. Mast cell stabilizers as well as specific tryptase and MCP1 inhibitors prevented the development of OIR in WT mice. Preterm infants with early retinopathy of prematurity had markedly higher plasma MCT levels than age-matched infants without disease, suggesting mast cells contribute to human disease. Together, these results suggest therapies that suppress mast cell activity should be further explored as a potential option for preventing eye diseases and subsequent blindness induced by neovascularization.
- リンク情報
- ID情報
-
- DOI : 10.1172/JCI89893
- ISSN : 0021-9738
- eISSN : 1558-8238
- PubMed ID : 28990934
- Web of Science ID : WOS:000414240400009