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Biochem Biophys Res Commun. 2014 Aug 22;451(2):314-8. doi: 10.1016/j.bbrc.2014.07.124. Epub 2014 Aug 2.

Ancient origin of mast cells.

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  • 1Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address:
  • 2Research Complex for the Medicine Frontiers, Aichi Medical University, Nagakute, Aichi 480 1195, Japan.
  • 3Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • 4Marine Genomics Unit, Okinawa Institute of Science and Technology Graduate University, Onna, Okinawa 904-0495, Japan.


The sentinel roles of mammalian mast cells (MCs) in varied infections raised the question of their evolutionary origin. We discovered that the test cells in the sea squirt Ciona intestinalis morphologically and histochemically resembled cutaneous human MCs. Like the latter, C. intestinalis test cells stored histamine and varied heparin·serine protease complexes in their granules. Moreover, they exocytosed these preformed mediators when exposed to compound 48/80. In support of the histamine data, a C. intestinalis-derived cDNA was isolated that resembled that which encodes histidine decarboxylase in human MCs. Like heparin-expressing mammalian MCs, activated test cells produced prostaglandin D2 and contained cDNAs that encode a protein that resembles the synthase needed for its biosynthesis in human MCs. The accumulated morphological, histochemical, biochemical, and molecular biology data suggest that the test cells in C. intestinalis are the counterparts of mammalian MCs that reside in varied connective tissues. The accumulated data point to an ancient origin of MCs that predates the emergence of the chordates >500million years ago, well before the development of adaptive immunity. The remarkable conservation of MCs throughout evolution is consistent with their importance in innate immunity.

Copyright © 2014 Elsevier Inc. All rights reserved.


Ciona intestinalis; Heparin; Histamine; Mast cell; Prostaglandin D(2); Serine protease

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