Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192 Japan.
Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192 Japan ; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Charlestown, MA 02129 USA.
J Intensive Care. 2016 Jul 22;4:48. doi: 10.1186/s40560-016-0177-9. eCollection 2016.
The aim of this study was to investigate the effects of recombinant human-soluble thrombomodulin (rTM) on lipopolysaccharide (LPS)-induced, platelet-dependent neutrophil extracellular trap (NET) formation (NETosis). Human peripheral blood neutrophils and platelets were co-incubated with or without LPS (0.2 μg/ml) in the presence and absence of rTM (2 μg/ml). NETosis was confirmed by immunostaining and confocal microscopy. In the absence of platelets, LPS did not induce NETosis in the neutrophils. NETosis, however, was induced by LPS when neutrophils were co-cultured with platelets (64 % of neutrophils). Notably, rTM was able to fully inhibit NETosis in neutrophils cultured with platelets and in the presence of LPS. rTM did not induce NETosis in this co-culture system (p < 0.01 versus LPS in the absence of rTM). These results show that rTM can suppress LPS-induced platelet-dependent NETosis in vitro.
本研究旨在探讨重组人可溶性血栓调节蛋白(rTM)对脂多糖(LPS)诱导的血小板依赖性中性粒细胞胞外诱捕网(NET)形成(NETosis)的影响。将人外周血中性粒细胞和血小板在存在和不存在 rTM(2μg/ml)的情况下与 LPS(0.2μg/ml)共同孵育。通过免疫染色和共聚焦显微镜确认 NETosis。在没有血小板的情况下,LPS 不会诱导中性粒细胞的 NETosis。然而,当中性粒细胞与血小板共培养时,LPS 会诱导 NETosis(64%的中性粒细胞)。值得注意的是,rTM 能够完全抑制与血小板共培养且存在 LPS 的中性粒细胞中的 NETosis。rTM 不会在该共培养系统中诱导 NETosis(与 LPS 不存在 rTM 的情况下相比,p<0.01)。这些结果表明,rTM 可抑制体外 LPS 诱导的血小板依赖性 NETosis。