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Research article2017Peer reviewedOpen access

Acidic pH is essential for maintaining mast cell secretory granule homeostasis

Pejler, Gunnar; Frisk, Jun Mei Hu; Sjostrom, Daniel; Paivandy, Aida; Ohrvik, Helena

Abstract

It has been recognized for a long time that the secretory granules of mast cells are acidic, but the functional importance of maintaining an acidic pH in the mast cell granules is not fully understood. Here we addressed this issue by examining the effects of raising the pH of the mast cell secretory granules. Mast cells were incubated with bafilomycin A1, an inhibitor of the vacuolar-type ATPase proton pump. Supporting a role of vacuolar-type ATPase in mast cell granule acidification, bafilomycin A1 treatment caused a robust increase in granule pH. This was accompanied by marked effects on mast cell granules, including swelling and acquisition of vacuole-like morphology. Moreover, bafilomycin A1 caused extensive, yet selective effects on the granule content. These included aberrant processing of pro-carboxypeptidase A3 and a reduction in the level of intracellular histamine, the latter being accompanied by an increase in extracellular histamine. In contrast, the storage of beta-hexosaminidase, a prototype lysosomal hydrolase known to be stored in mast cell granules, was not affected by abrogation of granule acidification. Moreover, bafilomycin A1 caused a reduction of tryptase enzymatic activity and appearance of tryptase degradation products. Tryptase inhibition prevented the formation of such degradation products, suggesting that the pH elevation causes tryptase to undergo autoproteolysis. Taken together, our findings reveal that mast cell secretory granule homeostasis is critically dependent on an acidic milieu.

Published in

Cell death and disease
2017, Volume: 8, article number: e2785
Publisher: NATURE PUBLISHING GROUP

      SLU Authors

          UKÄ Subject classification

          Cell Biology

          Publication identifier

          DOI: https://doi.org/10.1038/cddis.2017.206

          Permanent link to this page (URI)

          https://res.slu.se/id/publ/90484