ArticleThe Journal of experimental medicine2007
Molecular mechanism of mast cell mediated innate defense against endothelin and snake venom sarafotoxin.
Article in The Journal of experimental medicine, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 154 citations in OpenAlex.
- Mast cell proteases and their significance in physiology, pathology, and therapeutic approaches.Pharmacological reviews · 2026Review
- Maternal IgE Influence on Fetal and Infant Health.Immunological reviews · 2025Review
- LRO biogenesis and function: what can we learn from mast cells?Frontiers in cell and developmental biology · 2025Review
- Article
- Mast Cell Activation Syndrome Update-A Dermatological Perspective.Journal of personalized medicine · 2023Review
- Lung-specific MCEMP1 functions as an adaptor for KIT to promote SCF-mediated mast cell proliferation.Nature communications · 2023Article
- Mast cell-mediated immune regulation in health and disease.Frontiers in medicine · 2023Review
- Analysis of human lung mast cells by single cell RNA sequencing.Frontiers in immunology · 2023Article
- Carboxypeptidase A3 expression in canine mast cell tumors and tissue-resident mast cells.Veterinary pathology · 2022Article
- Review
- IgE antibodies increase honeybee venom responsiveness and detoxification efficiency of mast cells.Allergy · 2022Article
- Dynamically upregulated mast cell CPA3 patterns in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis.Frontiers in immunology · 2022Article
- Mast Cell and Basophil Granule Proteases -Frontiers in immunology · 2022Review
- Food Intolerance: The Role of Histamine.Nutrients · 2021Review
- Review
- Article
- Divergent Mast Cell Responses Modulate Antiviral Immunity During Influenza Virus Infection.Frontiers in cellular and infection microbiology · 2021Review
- Novel Strategies to Target Mast Cells in Disease.Journal of innate immunity · 2021Review
- Harnessing the Power of Mast Cells in unconventional Immunotherapy Strategies and Vaccine Adjuvants.Cells · 2020Review
- IgE Effector Mechanisms, in Concert with Mast Cells, Contribute to Acquired Host Defense against Staphylococcusaureus.Immunity · 2020Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mast cells are protective against snake venom sarafotoxins that belong to the endothelin (ET) peptide family. The molecular mechanism underlying this recently recognized innate defense pathway is unknown, but secretory granule proteases have been invoked. To specifically disrupt a single protease function without affecting expression of other proteases, we have generated a mouse mutant selectively lacking mast cell carboxypeptidase A (Mc-cpa) activity. Using this mutant, we have now identified Mc-cpa as the essential protective mast cell enzyme. Mass spectrometry of peptide substrates after cleavage by normal or mutant mast cells showed that removal of a single amino acid, the C-terminal tryptophan, from ET and sarafotoxin by Mc-cpa is the principle molecular mechanism underlying this very rapid mast cell response. Mast cell proteases can also cleave ET and sarafotoxin internally, but such "nicking" is not protective because intramolecular disulfide bridges maintain peptide function. We conclude that mast cells attack ET and sarafotoxin exactly at the structure required for toxicity, and hence sarafotoxins could not "evade" Mc-cpa's substrate specificity without loss of toxicity.
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