Mast cell hyperactivity underpins the development of oxygen-induced retinopathy
| Autor: | Yasuo Mori, Noriko Okamoto, Kyungsook Jung, Ryota Kakinuma, Uiko Kaku, Saori Ishizaka, Akane Tanaka, Kaoru Karasawa, Koujirou Yasui, Hiroshi Matsuda, Nobuyuki Onai, Eiichiro Noda, Yosuke Amagai, Masatoshi Kondo, Shinichi Yokota, Akira Matsuda, Hyosun Jang, Toshiaki Ohteki, Peter D. Arkwright, Kenshiro Matsuda, Kumiko Oida |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Mice 129 Strain Cell Degranulation Mice Transgenic Tryptase Inflammation Retinal Neovascularization Mouse models Neovascularization 03 medical and health sciences 0302 clinical medicine medicine Animals Humans Cells Cultured Sprouting angiogenesis biology business.industry Monocyte Infant Newborn Degranulation General Medicine Mast cell eye diseases Rats Mice Inbred C57BL Oxygen 030104 developmental biology medicine.anatomical_structure Mast cells 030221 ophthalmology & optometry biology.protein Cancer research Tryptases Angiogenesis medicine.symptom business Infant Premature Research Article |
| Zdroj: | The Journal of Clinical Investigation Matsuda, K, Okamoto, N, Kondo, M, Arkwright, P, Karasawa, K, Ishizaka, S, Yokota, S, Matsuda, A, Jung, K, Oida, K, Amagai, Y, Jang, H, Noda, E, Kakinuma, R, Yasui, K, Kaku, U, Mori, Y, Onai, N, Ohteki, T, Tanaka, A & Matsuda, H 2017, ' Mast cell hyperactivity underpins the development of oxygen-induced retinopathy ', The Journal of clinical investigation, vol. 127, no. 11, pp. 3987-4000 . https://doi.org/10.1172/JCI89893 |
| ISSN: | 1558-8238 0021-9738 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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