Granzyme B is expressed in mouse mast cells in vivo and in vitro and causes delayed cell death independent of perforin.
Mast cells respond to pathogens and allergens by secreting a vast array of preformed and newly synthesized mediators, including enzymes, vasoactive amines, lipid mediators, cytokines and chemokines, thereby affecting innate and adaptive immune responses and pathogenesis. Here, we present evidence that skin-, but not lung-associated primary mast cells as well as in vitro-differentiated bone marrow-derived mast cells (BMMC) express granzyme (gzm) B, but not gzmA or perforin (perf). GzmB is associated with cytoplasmic granules of BMMC and secreted after Fcepsilon-receptor-mediated activation. BMMC from wild type but not gzmB-deficient mice cause cell death in susceptible adherent target cells, indicating that the perf-independent cytotoxicity of BMMC is executed by gzmB. Furthermore, gzmB induces a disorganization of endothelial cell-cell contacts. The data suggest that activated mast cells contribute, via secreted gzmB, to cell death, increased vascular permeability, leukocyte extravasation and subsequent inflammatory processes in affected tissues.
Pardo
J
J
Metschnikoff Laboratory, Max-Planck-Institut for Immunbiology, Stübeweg 51, Freiburg, Germany.
Wallich
R
R
Ebnet
K
K
Iden
S
S
Zentgraf
H
H
Martin
P
P
Ekiciler
A
A
Prins
A
A
Müllbacher
A
A
Huber
M
M
Simon
M M
MM
D000818:Animals; D023102:Anoikis / Q000502:physiology; D017209:Apoptosis / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D053804:Granzymes / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000166:cytology; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054353:Perforin / Q000235:genetics / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism; D012867:Skin / Q000166:cytology
C485701:Fcgr1 protein, mouse; D017452:Receptors, IgG; D054353:Perforin; D053804:Granzymes