Journal
ACS CHEMICAL BIOLOGY
Volume 11, Issue 11, Pages 3077-3083Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acschembio.6b00616
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Funding
- National Institutes of Health New Innovator Award [1 DP2 OD004258-01]
- National Science Foundation Graduate Student Fellowship
- National Institutes of Health Chemistry Biology Interface Training Grant [GM 08700]
- University of Minnesota Doctoral Dissertation Fellowships
- NIGMS Biotechnology Training Program Fellowship [5T32GM008347-23]
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As tissue-resident immune cells, mast cells are frequently found in close proximity to afferent neurons and are subjected to immunoactive mediators secreted by these neurons, including substance P (SP) and calcitonin gene-related peptide (CGRP). Neurogenic inflammation is thought to play an important role in the pathophysiology of many diseases. Unraveling the cellular mechanisms at the interface between the immune response and the peripheral nervous system is important for understanding how these diseases arise and progress. In this work, mast cell degranulation following direct exposure to CGRP and SP was studied both at the bulk and single-cell levels to characterize the mouse peritoneal mast cell response to neuropeptides and compare this response to well-studied mast cell activation pathways. Results show that mast cells chemical messenger-filled granules with increased IgE preincubation concentrations. The biophysical characteristics of mast cell degranulation in response to SP and CGRP is in many ways similar to calcium ionophore-induced mast cell degranulation; however, neuropeptide-stimulated mast cells secrete reduced chemical messenger content per secretion event, resulting in an overall relative decrease in secreted chemical messengers.
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