Platelet Granzyme B expression is increased in sepsis: a potential mechanism for sepsis‐associated endothelial apoptosis

Abstract

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.