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Heightened Anaphylaxis Reaction in Female Mice is Associated with Increased Synthesis of Mast Cell Secretory Granule‐Associated Immune Mediators
Author(s) -
Mackey Emily,
D'Costa Susan,
Pohl Calvin,
Ayyadurai Saravanan,
Laster Scott,
Moeser Adam James
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1023.1
Subject(s) - mediator , immune system , degranulation , granule (geology) , immunology , mast cell , irritable bowel syndrome , immunoglobulin e , inflammation , biology , allergy , endocrinology , medicine , antibody , receptor , paleontology
Sex is a critical determinant in the prevalence and severity of many diseases. In particular mast cell (MC)‐associated diseases, including irritable bowel syndrome (IBS) and IgE‐mediated allergy, are more prevalent in females. Our previous studies with murine and porcine allergy and stress models demonstrated that females exhibit more severe anaphylaxis and MC‐mediated intestinal permeability. We hypothesized that heightened disease responses in females are associated with sex‐specific differences in MC reactivity. Our objective was to determine whether MCs exhibit sex‐specific differences. Utilizing bone marrow‐derived mast cells (BMMCs) derived from female and male mice, we showed that female BMMCs exhibited greater mediator release than male BMMCs in response MC stimuli. Further experiments revealed that heightened MC granule mediator release in females was not due to increased MC degranulation signaling, but a result of female MCs increased capacity to store granule mediators. To investigate a mechanism for increased mediator content in female MCs, we performed transcriptional analysis of male and female BMMCs. Results from sequencing revealed that female MCs demonstrated higher expression of genes related to mediator synthesis and secretory granule maturation processes. Taken together, these data revealed that female MCs have increased storage of mediators, likely due to the higher expression of genes related to mediator synthesis and granule maturation factors. The findings are in line with the heightened anaphylactic response found in female mice. Uncovering the mechanism responsible for sex‐dependent differences in MCs could allow for the development of sex‐specific and more effective treatments for MC‐associated diseases. Support or Funding Information This research was supported, in part, by the following grants from the National Institutes of Health: R01 HD072968 (AJM), R03 DK097462 (AJM), and T35 OD011070 (EM)