Abstract

Mast cells are emerging as players in the communication between peripheral nerve endings and cells of the immune system. However, it is not clear the mechanism by which mast cells communicate with peripheral nerves. We previously found that mast cells located within healing tendons can express glutamate receptors, raising the possibility that mast cells may be sensitive to glutamate signaling. To evaluate this hypothesis, we stimulated primary mast cells with glutamate and showed that glutamate induced the profound upregulation of a panel of glutamate receptors of both the ionotropic type (NMDAR1, NMDAR2A, and NMDAR2B) and the metabotropic type (mGluR2 and mGluR7) at both the mRNA and protein levels. The binding of glutamate to glutamate receptors on the mast cell surface was confirmed. Further, glutamate had extensive effects on gene expression in the mast cells, including the upregulation of pro-inflammatory components such as IL-6 and CCL2. Glutamate also induced the upregulation of transcription factors, including Egr2, Egr3 and, in particular, FosB. The extensive induction of FosB was confirmed by immunofluorescence assessment. Glutamate receptor antagonists abrogated the responses of the mast cells to glutamate, supporting the supposition of a functional glutamate-glutamate receptor axis in mast cells. Finally, we provide in vivo evidence supporting a functional glutamate-glutamate receptor axis in the mast cells of injured tendons. Together, these findings establish glutamate as an effector of mast cell function, thereby introducing a novel principle for how cells in the immune system can communicate with nerve cells.

Keywords

Glutamate; Glutamate receptors; Mast cells; NMDA receptors; Tryptase

Published in

Cellular and Molecular Immunology
2021, Volume: 18, number: 10, pages: 2383-2392
Publisher: NATURE PUBLISHING GROUP

SLU Authors

• Pejler, Gunnar

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    
  • Uppsala University

UKÄ Subject classification

Immunology in the medical area


Publication identifier

DOI: https://doi.org/10.1038/s41423-020-0421-z

Permanent link to this page (URI)

https://res.slu.se/id/publ/105417