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Protease Mediators of Anaphylaxis

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Abstract

This chapter reviews the history of studies of mast cell and basophil protease biology and attempts to synthesize current concepts bearing upon their likely contributions to anaphylaxis, focusing on enzymes in the histamine-rich intracellular granules in humans and rodents. As a class, peptidases and proteases are the major proteins of mast cell secretory granules, but seem to be less abundant in basophil granules. The peptidases are secreted with histamine during anaphylactic degranulation. Typically, they are cationic proteins that are packaged in the granule with polyanionic heparin and chondroitin sulfate proteoglycans, and are released in association with them. The peptidases, which differ widely in mechanistic class and substrate specificity, include serine endopeptidases (e.g., chymases, cathepsin G, and tryptases), metallo-exopeptidases (e.g., carboxypeptidase A3), and thiol peptidases (e.g., dipeptidylpeptidase I/cathepsin C). There are potentially important differences between human and rodent mast cell and basophil peptidases in variety and functions. Some of these peptidases have anti-inflammatory as well as inflammatory potential, with roles in host defense. When originating from the secretory granule, most are active at the time of release, but their fates and potential for causing harm outside of the cell differ widely, with some enzymes remaining associated with the cell membrane, or being free but promptly inactivated, and others remaining active and capable of cleaving targets remote from the site of degranulation – indeed, acting systemically. Because of their abundance, several of the chymases and tryptases are biomarkers of anaphylaxis. Beyond their demonstrated utility in this regard, some of the peptidases may contribute to the pathology of anaphylaxis and are under investigation as targets for therapeutic inhibition.

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  1. Medicine and Cardiovascular Research Institute, University of California at San Francisco, San Francisco, CA, USA

    George H. Caughey

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  1. Harvard Medical School, Ambulatory Center, Brigham and Women’s Hospital, Boyleston Street, Route 9 850, Chestnut Hill, 02467, Massachusetts, USA

    Mariana C. Castells

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Caughey, G.H. (2011). Protease Mediators of Anaphylaxis. In: Castells, M. (eds) Anaphylaxis and Hypersensitivity Reactions. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-951-2_6

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