Protective role of protease-activated receptor-2 in anaphylaxis model mice.
Anaphylaxis is a severe life-threatening hypersensitivity reaction induced by mast cell degranulation. Among the various mediators of mast cells, little is known about the role of tryptase. Therefore, we aimed to elucidate the role of protease-activating receptor-2 (PAR-2), a receptor activated by t...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0283915&type=printable |
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| author | Maho Nakazawa Ryota Tochinai Wataru Fujii Mao Komori Tomohiro Yonezawa Yasuyuki Momoi Shingo Maeda |
| author_facet | Maho Nakazawa Ryota Tochinai Wataru Fujii Mao Komori Tomohiro Yonezawa Yasuyuki Momoi Shingo Maeda |
| author_sort | Maho Nakazawa |
| collection | DOAJ |
| description | Anaphylaxis is a severe life-threatening hypersensitivity reaction induced by mast cell degranulation. Among the various mediators of mast cells, little is known about the role of tryptase. Therefore, we aimed to elucidate the role of protease-activating receptor-2 (PAR-2), a receptor activated by tryptase, in murine anaphylactic models using PAR-2-deficient mice and newly generated tryptase-deficient mice. Anaphylaxis was induced by IgE-dependent and IgE-independent mast cell degranulation in mice. PAR-2 deficiency exacerbated the decrease in body temperature and hypotension during anaphylaxis; however, the number of skin mast cells, degree of mast cell degranulation, and systemic and local vascular hyperpermeability were comparable in PAR-2 knockout and wild-type mice. Nitric oxide, which is produced by endothelial nitric oxide synthase (eNOS), is an indispensable vasodilator in anaphylaxis. In the lungs of anaphylactic mice, PAR-2 deficiency promoted eNOS expression and phosphorylation, suggesting a protective effect of PAR-2 against anaphylaxis by downregulating eNOS activation and expression. Based on the hypothesis that the ligand for PAR-2 in anaphylaxis is mast cell tryptase, tryptase-deficient mice were generated using CRISPR-Cas9. In wild-type mice, the PAR-2 antagonist exacerbated the body temperature drop due to anaphylaxis; however, the effect of the PAR-2 antagonist was abolished in tryptase-deficient mice. These results suggest that tryptase is a possible ligand of PAR-2 in anaphylaxis and that the tryptase/PAR-2 pathway attenuates the anaphylactic response in mice. |
| first_indexed | 2024-04-24T06:03:15Z |
| format | Article |
| id | doaj.art-904d832265e349ca868f3539a3eeaa7c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-24T06:03:15Z |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-904d832265e349ca868f3539a3eeaa7c2024-04-23T05:31:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01194e028391510.1371/journal.pone.0283915Protective role of protease-activated receptor-2 in anaphylaxis model mice.Maho NakazawaRyota TochinaiWataru FujiiMao KomoriTomohiro YonezawaYasuyuki MomoiShingo MaedaAnaphylaxis is a severe life-threatening hypersensitivity reaction induced by mast cell degranulation. Among the various mediators of mast cells, little is known about the role of tryptase. Therefore, we aimed to elucidate the role of protease-activating receptor-2 (PAR-2), a receptor activated by tryptase, in murine anaphylactic models using PAR-2-deficient mice and newly generated tryptase-deficient mice. Anaphylaxis was induced by IgE-dependent and IgE-independent mast cell degranulation in mice. PAR-2 deficiency exacerbated the decrease in body temperature and hypotension during anaphylaxis; however, the number of skin mast cells, degree of mast cell degranulation, and systemic and local vascular hyperpermeability were comparable in PAR-2 knockout and wild-type mice. Nitric oxide, which is produced by endothelial nitric oxide synthase (eNOS), is an indispensable vasodilator in anaphylaxis. In the lungs of anaphylactic mice, PAR-2 deficiency promoted eNOS expression and phosphorylation, suggesting a protective effect of PAR-2 against anaphylaxis by downregulating eNOS activation and expression. Based on the hypothesis that the ligand for PAR-2 in anaphylaxis is mast cell tryptase, tryptase-deficient mice were generated using CRISPR-Cas9. In wild-type mice, the PAR-2 antagonist exacerbated the body temperature drop due to anaphylaxis; however, the effect of the PAR-2 antagonist was abolished in tryptase-deficient mice. These results suggest that tryptase is a possible ligand of PAR-2 in anaphylaxis and that the tryptase/PAR-2 pathway attenuates the anaphylactic response in mice.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0283915&type=printable |
| spellingShingle | Maho Nakazawa Ryota Tochinai Wataru Fujii Mao Komori Tomohiro Yonezawa Yasuyuki Momoi Shingo Maeda Protective role of protease-activated receptor-2 in anaphylaxis model mice. PLoS ONE |
| title | Protective role of protease-activated receptor-2 in anaphylaxis model mice. |
| title_full | Protective role of protease-activated receptor-2 in anaphylaxis model mice. |
| title_fullStr | Protective role of protease-activated receptor-2 in anaphylaxis model mice. |
| title_full_unstemmed | Protective role of protease-activated receptor-2 in anaphylaxis model mice. |
| title_short | Protective role of protease-activated receptor-2 in anaphylaxis model mice. |
| title_sort | protective role of protease activated receptor 2 in anaphylaxis model mice |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0283915&type=printable |
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