title: Granzyme D is a novel murine mast cell protease that is highly induced by multiple pathways of mast cell activation.
abstract: Granzymes 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.
authors.affiliation: Swedish University of Agricultural Sciences, Department of Anatomy, Physiology and Biochemistry, Uppsala, Sweden. Elin.Ronnberg@afb.slu.se
authors.forename: Elin
authors.initials: E
authors.lastname: Rönnberg
authors.forename: Gabriela
authors.initials: G
authors.lastname: Calounova
authors.forename: Bengt
authors.initials: B
authors.lastname: Guss
authors.forename: Anders
authors.initials: A
authors.lastname: Lundequist
authors.forename: Gunnar
authors.initials: G
authors.lastname: Pejler
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D018920:Coculture Techniques; D004789:Enzyme Activation / Q000502:physiology*; D004926:Escherichia coli; D006094:Gram-Positive Bacteria; D053804:Granzymes / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides; D008407:Mast Cells / Q000201:enzymology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018502:Streptococcus equi; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D053804:Granzymes; C056483:Gzmd protein, mouse