Nuclear Receptor 4a3 (Nr4a3) Regulates Murine Mast Cell Responses and Granule Content

ABSTRACTGranzymes are serine proteases known mostly for their role in the induction of apoptosis. Granzymes A and B have been extensively studied, but relatively little is known about granzymes C to G and K to M. T cells, lymphohematopoietic stromal cells, and granulated metrial gland cells express granzyme D, but the function of granzyme D is unknown. Here we show that granzyme D is expressed by murine mast cells and that its level of expression correlates positively with the extent of mast cell maturation. Coculture of mast cells with live, Gram-positive bacteria caused a profound, Toll-like receptor 2 (TLR2)-dependent induction of granzyme D expression. Granzyme D expression was also induced by isolated bacterial cell wall components, including lipopolysaccharide (LPS) and peptidoglycan, and by stem cell factor, IgE receptor cross-linking, and calcium ionophore stimulation. Granzyme D was released into the medium in response to mast cell activation. Granzyme D induction was dependent on protein kinase C and nuclear factor of activated T cells (NFAT). Together, these findings identify granzyme D as a novel murine mast cell protease and implicate granzyme D in settings where mast cells are activated, such as bacterial infection and allergy.

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[41] Murine mast cell growth factor

Methods in Enzymology - Immunochemical Techniques Part H ◽

10.1016/s0076-6879(85)16043-x ◽

1985 ◽

pp. 553-563 ◽

Cited By ~ 1

Author(s):

Yee-Pang Yung ◽

Karl Welte

Keyword(s):

Mast Cell ◽

Growth Factor ◽

Cell Growth ◽

Murine Mast Cell ◽

Mast Cell Growth Factor

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Mast Cell Responses to Viruses and Pathogen Products

International Journal of Molecular Sciences ◽

10.3390/ijms20174241 ◽

2019 ◽

Vol 20 (17) ◽

pp. 4241 ◽

Cited By ~ 21

Author(s):

Jean S. Marshall ◽

Liliana Portales-Cervantes ◽

Edwin Leong

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Immune Responses ◽

Viral Infection ◽

Viral Infections ◽

Inflammatory Responses ◽

Local Source ◽

Type I ◽

Viral Challenge ◽

Cell Responses

Mast cells are well accepted as important sentinel cells for host defence against selected pathogens. Their location at mucosal surfaces and ability to mobilize multiple aspects of early immune responses makes them critical contributors to effective immunity in several experimental settings. However, the interactions of mast cells with viruses and pathogen products are complex and can have both detrimental and positive impacts. There is substantial evidence for mast cell mobilization and activation of effector cells and mobilization of dendritic cells following viral challenge. These cells are a major and under-appreciated local source of type I and III interferons following viral challenge. However, mast cells have also been implicated in inappropriate inflammatory responses, long term fibrosis, and vascular leakage associated with viral infections. Progress in combating infection and boosting effective immunity requires a better understanding of mast cell responses to viral infection and the pathogen products and receptors we can employ to modify such responses. In this review, we outline some of the key known responses of mast cells to viral infection and their major responses to pathogen products. We have placed an emphasis on data obtained from human mast cells and aim to provide a framework for considering the complex interactions between mast cells and pathogens with a view to exploiting this knowledge therapeutically. Long-lived resident mast cells and their responses to viruses and pathogen products provide excellent opportunities to modify local immune responses that remain to be fully exploited in cancer immunotherapy, vaccination, and treatment of infectious diseases.

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