{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:03:01Z","timestamp":1790856181789,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Extensive activation of mast cells is the major switch that triggers systemic anaphylaxis, resulting in the subsequent release of anaphylactic mediators into circulation. We previously demonstrated that rapid changes in oxygen tension lead to mast cell degranulation, and the released tryptase triggers retinal angiogenesis in a murine oxygen-induced retinopathy model. However, whether a rapid shift from hyperoxia to normoxia (relative hypoxic stress) is a risk factor for systemic anaphylaxis remains unknown. In this study, we demonstrated that the relative hypoxia stress induces systemic mast cell activation via transient receptor potential ankyrin 1 (TRPA1) channels, which immediately leads to hypothermia and increased vascular permeability in adult mice. Although mast cell\u2013deficient or TRPA1-deficient mice did not exhibit anaphylactic symptoms following a rapid sift to normoxia, preinjection with bone marrow\u2013derived cultured mast cells (BMCMCs) derived from wild-type TRPA1-expressing mice restored anaphylactic responses. In addition, we found that the rapid reductions in oxygen tension in a culture atmosphere triggered the degranulation of BMCMCs derived from wild-type TRPA1-expressing mice but not that of BMCMCs derived from TRPA1-deficient mice. In human LAD2 mast cells, the relative hypoxic stress led to the degranulation, which was suppressed by the addition of a TRPA1 inhibitor. Gradual reductions from hyperoxia to normoxia led to no anaphylactic symptoms. Our results demonstrated that TRPA1-triggered mast cell degranulation is a novel pathway that induces anaphylactic shock without Ag\u2013Ab reactions. These findings introduce a potential role for oxygen in inducing mast cell\u2013dependent anaphylaxis and highlight the need to reconsider chronic pure oxygen therapy for anoxic diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.2000149","type":"journal-article","created":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T19:40:11Z","timestamp":1603482011000},"page":"2959-2967","source":"Crossref","is-referenced-by-count":10,"title":["A Rapid Shift from Chronic Hyperoxia to Normoxia Induces Systemic Anaphylaxis via Transient Receptor Potential Ankyrin 1 Channels on Mast Cells"],"prefix":"10.1093","volume":"205","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7960-1663","authenticated-orcid":false,"given":"Kenshiro","family":"Matsuda","sequence":"first","affiliation":[{"name":"Laboratory of Comparative Animal Medicine, Division of Animal Life Science, Institute of Agriculture, Tokyo University of Agriculture and Technology , Tokyo 183-8509 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7411-5375","authenticated-orcid":false,"given":"Peter D","family":"Arkwright","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunity and Inflammation, University of Manchester , Manchester M13 9WL ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University , Kyoto 615-8510 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6832-3242","authenticated-orcid":false,"given":"Masa-aki","family":"Oikawa","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Laboratory, Equine Veterinary Medical Center , Doha ,","place":["Qatar"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9129-0397","authenticated-orcid":false,"given":"Ryo","family":"Muko","sequence":"additional","affiliation":[{"name":"Cooperative Major in Advanced Health Science, Graduate School of Bio-Applications and System Engineering, Tokyo University of Agriculture and Technology , Tokyo 183-8509 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akane","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Laboratory of Comparative Animal Medicine, Division of Animal Life Science, Institute of Agriculture, Tokyo University of Agriculture and Technology , Tokyo 183-8509 ,","place":["Japan"]},{"name":"Cooperative Major in Advanced Health Science, Graduate School of Bio-Applications and System Engineering, Tokyo University of Agriculture and Technology , Tokyo 183-8509 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3189-6842","authenticated-orcid":false,"given":"Hiroshi","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Laboratory of Comparative Animal Medicine, Division of Animal Life Science, Institute of Agriculture, Tokyo University of Agriculture and Technology , Tokyo 183-8509 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,1]]},"reference":[{"key":"2025030417505846300_r1","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.jaci.2005.12.1303","article-title":"Second symposium on the definition and management of anaphylaxis: summary report--second National Institute of Allergy and Infectious Disease\/Food Allergy and Anaphylaxis Network symposium","volume":"117","author":"Sampson","year":"2006","journal-title":"J. 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