Thrombospondin-1 contributes to mortality in murine sepsis through effects on innate immunity.
Thrombospondin-1 contributes to mortality in murine sepsis through effects on innate immunity.
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DOI：
10.1371/journal.pone.0019654
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发表时间：
2011-05-09
期刊：
影响因子：
3.7
通讯作者：
Ali NA
中科院分区：
文献类型：
--
作者：
McMaken S;Exline MC;Mehta P;Piper M;Wang Y;Fischer SN;Newland CA;Schrader CA;Balser SR;Sarkar A;Baran CP;Marsh CB;Cook CH;Phillips GS;Ali NA
凝血酶敏感蛋白-1(TSP-1)参与多种生物学过程，包括免疫和组织损伤反应，但其在脓毒症中的作用尚不清楚。脓毒症时，血小板表面TSP-1的表达增加，并可激活影响预后的抗炎细胞因子转化生长因子β-1。由于这些观察，我们试图确定TSP-1在脓毒症中的重要性。我们对TSP-1缺失和野生型(WT)C57BL/6J小鼠进行了研究，以确定TSP-1在脓毒症中的重要性。我们采用盲肠结扎穿刺法(CLP)和腹膜腔内注射(IP)E.coli法建立腹膜脓毒症模型。此外，用骨髓来源的巨噬细胞(BMM)测定吞噬活性。TSP-1−/−动物的死亡率低于WT小鼠。组织和腹腔灌洗液中转化生长因子β-1水平在各基因型动物间无明显变化。此外，两组动物的主要先天细胞因子水平没有差异。经CLP后，WT小鼠的PLF细菌载量高于TSP-1−/−小鼠。当进行IP E.Coli注射时，TSP-1−/−动物的生存优势持续存在。与WT相比，TSP-1−/−骨髓基质细胞的吞噬能力增强。TSP-1缺乏在两种腹膜脓毒症小鼠模型中具有保护作用，不依赖转化生长因子β-1的激活。我们的研究表明，TSP-1的表达与WT小鼠的吞噬功能降低和细菌清除有关，从而导致腹膜炎症和死亡率的增加。这些数据支持这样一种观点，即应该在人类条件下更充分地研究TSP-1。
Thrombospondin-1 (TSP-1) is involved in many biological processes, including immune and tissue injury response, but its role in sepsis is unknown. Cell surface expression of TSP-1 on platelets is increased in sepsis and could activate the anti-inflammatory cytokine transforming growth factor beta (TGFβ1) affecting outcome. Because of these observations we sought to determine the importance of TSP-1 in sepsis. We performed studies on TSP-1 null and wild type (WT) C57BL/6J mice to determine the importance of TSP-1 in sepsis. We utilized the cecal ligation puncture (CLP) and intraperitoneal E.coli injection (IP E.coli) models of peritoneal sepsis. Additionally, bone-marrow-derived macrophages (BMMs) were used to determine phagocytic activity. TSP-1−/− animals experienced lower mortality than WT mice after CLP. Tissue and peritoneal lavage TGFβ1 levels were unchanged between animals of each genotype. In addition, there is no difference between the levels of major innate cytokines between the two groups of animals. PLF from WT mice contained a greater bacterial load than TSP-1−/− mice after CLP. The survival advantage for TSP-1−/− animals persisted when IP E.coli injections were performed. TSP-1−/− BMMs had increased phagocytic capacity compared to WT. TSP-1 deficiency was protective in two murine models of peritoneal sepsis, independent of TGFβ1 activation. Our studies suggest TSP-1 expression is associated with decreased phagocytosis and possibly bacterial clearance, leading to increased peritoneal inflammation and mortality in WT mice. These data support the contention that TSP-1 should be more fully explored in the human condition.
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潜伏期相关的肽具有与TGF-BETA1无关的体外和体内免疫作用。
影响因子：
3.7
作者：
Ali NA;Gaughan AA;Orosz CG;Baran CP;McMaken S;Wang Y;Eubank TD;Hunter M;Lichtenberger FJ;Flavahan NA;Lawler J;Marsh CB
通讯作者：
Marsh CB
影响因子：
15.9
作者：
Lawler, J;Sunday, M;Hynes, RO
通讯作者：
Hynes, RO
影响因子：
11.2
作者：
Martin-Manso G;Galli S;Ridnour LA;Tsokos M;Wink DA;Roberts DD
通讯作者：
Roberts DD
影响因子：
15.9
作者：
Pittet, JF;Griffiths, MJD;Sheppard, D
通讯作者：
Sheppard, D
DOI：
10.1073/pnas.88.11.5026
发表时间：
1991-06-01
影响因子：
11.1
作者：
IRUELAARISPE, ML;BORNSTEIN, P;SAGE, H
通讯作者：
SAGE, H