Lee Po-Shun, Waxman Aaron B, Cotich Kara L, Chung Su Wol, Perrella Mark A, Stossel Thomas P
Pulmonary and Critical Care Division Brigham and Women's Hospital, Boston, MA, USA.
Crit Care Med. 2007 Mar;35(3):849-55. doi: 10.1097/01.CCM.0000253815.26311.24.
Plasma gelsolin is a circulating actin-binding protein that serves a protective role against tissue injuries. Depletion of plasma gelsolin in systemic inflammation may contribute to adverse outcomes. We examined the role of plasma gelsolin in animal models of sepsis.
Animal and laboratory experiments.
Academic research laboratory.
Adult male mice.
Mice subjected to endotoxin or cecal ligation and puncture (CLP) were treated with exogenous plasma gelsolin or placebo.
We document the depletion of plasma gelsolin (25-50% of normal) in murine models of sepsis associated with the presence of circulating actin within 6 hrs of septic challenge. Repletion of plasma gelsolin leads to solubilization of circulating actin aggregates and significantly reduces mortality in endotoxemic mice (survival rates were 88% in the gelsolin group vs. 0% in the saline group, p < .001) and in CLP-challenged mice (survival rates were 30% in the gelsolin group vs. 0% in the saline group, p = .001). Plasma gelsolin repletion also shifted the cytokine profile of endotoxemic mice toward anti-inflammatory (plasma interleukin-10 levels were 205 +/- 108 pg/mL in the gelsolin group vs. 39 +/- 29 pg/mL in the saline group, p = .02).
We propose that circulation of particulate actin is a marker for sepsis-induced cell injury, that plasma gelsolin has a crucial protective role in sepsis, and that gelsolin replacement represents a potential therapy for this common lethal condition.
血浆凝溶胶蛋白是一种循环肌动蛋白结合蛋白，对组织损伤起保护作用。全身炎症反应时血浆凝溶胶蛋白的减少可能导致不良后果。我们研究了血浆凝溶胶蛋白在脓毒症动物模型中的作用。
动物和实验室实验。
学术研究实验室。
成年雄性小鼠。
对内毒素或盲肠结扎穿刺（CLP）处理的小鼠给予外源性血浆凝溶胶蛋白或安慰剂治疗。
我们记录了脓毒症小鼠模型中血浆凝溶胶蛋白的减少（降至正常水平的25 - 50%），脓毒症激发后6小时内伴有循环肌动蛋白的出现。补充血浆凝溶胶蛋白可使循环肌动蛋白聚集体溶解，并显著降低内毒素血症小鼠的死亡率（凝溶胶蛋白组存活率为88%，生理盐水组为0%，p < 0.001）以及CLP激发小鼠的死亡率（凝溶胶蛋白组存活率为30%，生理盐水组为0%，p = 0.001）。补充血浆凝溶胶蛋白还使内毒素血症小鼠的细胞因子谱向抗炎方向转变（凝溶胶蛋白组血浆白细胞介素-10水平为205±108 pg/mL，生理盐水组为39±29 pg/mL，p = 0.02）。
我们提出颗粒状肌动蛋白的循环是脓毒症诱导细胞损伤的一个标志物，血浆凝溶胶蛋白在脓毒症中具有关键的保护作用，补充凝溶胶蛋白是治疗这种常见致命病症的一种潜在疗法。
