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Platelet Granzyme B expression is increased in sepsis: a potential mechanism for sepsis‐associated endothelial apoptosis
Author(s) -
Freishtat Robert J,
Natale JoAnne,
Cohen Joanna S,
Sachdeva Reecha,
De Biase Lindsay M,
Ngor Eunis,
Degnan Andrew,
Benton Angela S,
Chow Matthew,
Kristosturyan Ervand,
Hoffman Eric P
Publication year - 2007
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.21.6.a1125-c
Subject(s) - sepsis , platelet , apoptosis , granzyme b , flow cytometry , intracellular , immunology , platelet activation , endothelial stem cell , medicine , microbiology and biotechnology , biology , immune system , t cell , biochemistry , in vitro
Platelets induce endothelial cell apoptosis via TGFβ1. We hypothesized that platelets are capable of inducing endothelial cell apoptosis in sepsis via up‐regulation of other platelet cell death mediators. BALB/c mice were bled 0 and 24h after cecal‐ligation and puncture. All mice developed signs of sepsis. PLT cDNA microarrays showed up‐regulation of 13 cell death mediators (GO:0008219), particularly a 10‐fold up‐regulation of pro‐apoptotic, Granzyme (Gzm) B (p=0.06), validated by RT‐PCR [24h:0h relative expression (mean±SE) = 10.12±0.07, p=0.04]. This correlated well with megakaryocytic mRNA sampled at the same time points (r=0.996). Flow cytometry of whole blood, gated on platelets by forward/side‐scatter properties, showed 0h intracellular GzmB expression of 4.4±1.3%. At 24h, 19.6±6.3% of platelets expressed intracellular GzmB(p=0.04). These data show platelets up‐regulate GzmB expression in a mouse model of severe sepsis. This supports the hypothesis that platelets are capable of inducing endothelial apoptosis in sepsis. If GzmB‐mediated apoptosis is supported by our ongoing functional studies, this would provide a novel target for sepsis therapy.