کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6001606 1182953 2015 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The effect of plasma-derived activated protein C on leukocyte cell-death and vascular endothelial damage
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
The effect of plasma-derived activated protein C on leukocyte cell-death and vascular endothelial damage
چکیده انگلیسی


- Vascular endothelial damage in LPS-induced sepsis model is attenuated by pd-APC.
- High-dose pd-APC increases the risk of bleeding.
- Increased circulating DAMPs such as nucleosome and HMGB1 are decreased by pd-APC.
- LPS-induced neutrophil cell-death and NETosis are suppressed by pd-APC.

IntroductionThe role of leukocyte and its death in the progression in inflammation attracts attention nowadays. The purpose of this study is to examine the effects of activated protein C (APC) on leucocyte cell death and vascular endothelial damage in sepsis.MethodsWistar rats were infused with lipopolysaccharide (8.0 mg/kg) concomitantly with either a low dose (0.5 mg/kg), a high dose (5.0 mg/kg) of plasma-derived APC or albumin. One and 3 hours after the injections, the mesenteric microcirculation was observed by intravital microscopy. The serum levels of nucleosome and High Mobility Group Box 1 (HMGB1) were measured in each group. In another series, cultured leukocyte cell-death in the medium supplemented with serum obtained from each group was examined in vitro.ResultsMicrocirculatory disturbance was significantly suppressed in both the high-dose and low-dose groups compared to the control group (P < 0.01, 0.05, respectively). The bleeding area was significantly increased in the control and high-dose groups (P < 0.05, 0.01, respectively). Serum levels of cell death markers such as nucleosome and HMGB1 were significantly decreased in the treatment groups (P < 0.01), and the protective effect was more pronounced in high-dose group. Cell death suppression was most prominent in high-dose group and the formation of neutrophil extracellular traps (NETs) was significantly suppressed in the treatment groups. Conclusion: Low-dose plasma-derived APC exerted protective effects on the microcirculation without increasing the risk of bleeding. The protective effect against leukocyte cell death and the suppressive effect on NETs formation of APC might be related to its beneficial effects.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Thrombosis Research - Volume 135, Issue 5, May 2015, Pages 963-969
نویسندگان
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