Discordance between microvascular permeability and leukocyte dynamics in septic inducible nitric oxide synthase deficient mice.
Discordance between microvascular permeability and leukocyte dynamics in septic inducible nitric oxide synthase deficient mice.
复制标题
DOI：
10.1186/cc6190
复制
发表时间：
2007
期刊：
影响因子：
15.1
通讯作者：
Parrillo, Joseph E.
中科院分区：
文献类型：
--
作者：
Hollenberg, Steven M.;Guglielmi, Massimiliano;Parrillo, Joseph E.
微血管功能障碍导致血管内液体和蛋白质渗漏，导致脓毒症中的低血压和休克。我们测试了这样的假设：废除诱导型一氧化氮合酶 (iNOS) 激活会减少败血症中的白细胞滚动、白细胞粘附和微血管渗漏。我们将盲肠结扎和穿刺导致败血症的野生型小鼠与缺乏 iNOS 的小鼠进行了比较。在 C57Bl/6 小鼠中通过盲肠结扎和穿刺诱导败血症后 15 至 20 小时，通过荧光活体显微镜同时评估提睾肌中的白细胞动态和微血管通透性。在单个非分支小静脉（25至40μm）中测量罗丹明标记的白细胞的滚动和粘附以及异硫氰酸荧光素结合的白蛋白的渗漏，并在脓毒症野生型、脓毒症iNOS缺陷转基因小鼠和假手术对照小鼠之间进行比较。与对照动物（分别为 8.5 ± 2.3 细胞/分钟和 1.1 ± 0.2 细胞/100 μm/分钟；两者 P < 0.001）相比，脓毒症动物的白细胞滚动和粘附增加（分别为 61.6 ± 14.4 细胞/分钟和 4.1 ± 0.6 细胞/100 μm/分钟）。 iNOS 缺陷型脓毒症小鼠的滚动增加（与野生型脓毒症小鼠相比，达到 105.5 ± 30.0 个细胞/分钟，P = 0.048）；粘附力未改变（5.1 ± 0.5 个细胞/100 μm 每分钟，P = 0.30）。与对照组相比，脓毒症导致野生型脓毒症小鼠的渗漏率增加（0.36 ± 0.05 vs 0.08 ± 0.01，P < 0.001）。 iNOS 缺陷型脓毒症小鼠中的渗漏减弱（与野生型脓毒症小鼠相比，0.12 ± 0.02，P < 0.001）。在这种情况下，白细胞粘附和血管渗漏不一致。研究发现，尽管白细胞粘附力相应增加，但脓毒症 iNOS 缺陷小鼠的微血管渗漏量比野生型脓毒症小鼠少，这表明一氧化氮在脓毒症期间调节血管通透性方面发挥着重要作用。
Microvascular dysfunction causing intravascular leakage of fluid and protein contributes to hypotension and shock in sepsis. We tested the hypothesis that abrogation of inducible nitric oxide synthase (iNOS) activation would decrease leukocyte rolling, leukocyte adhesion, and microvascular leakage in sepsis. We compared wild-type mice made septic by cecal ligation and puncture with mice deficient in iNOS. Leukocyte dynamics and microvascular permeability were assessed simultaneously by fluorescence intravital microscopy in the cremaster muscle 15 to 20 hours after induction of sepsis by cecal ligation and puncture in C57Bl/6 mice. Rolling and adhesion of leukocytes labeled with rhodamine and leakage of fluorescein isothiocyanate-conjugated albumin was measured in single nonbranching venules (25 to 40 μm) and compared among septic wild-type, septic iNOS-deficient transgenic, and sham-operated control mice. Leukocyte rolling and adhesion were increased in septic animals (61.6 ± 14.4 cells/minute and 4.1 ± 0.6 cells/100 μm per minute, respectively) as compared with control animals (8.5 ± 2.3 cells/minute and 1.1 ± 0.2 cells/100 μm per minute, respectively; P < 0.001 for both). Rolling increased in iNOS-deficient septic mice (to 105.5 ± 30.0 cells/minute, P = 0.048, versus wild-type septic); adhesion was unchanged (5.1 ± 0.5 cells/100 μm per minute, P = 0.30). Sepsis produced an increase in leakage ratio in wild-type septic mice compared with controls (0.36 ± 0.05 versus 0.08 ± 0.01, P < 0.001). Leakage was attenuated in iNOS-deficient septic mice (0.12 ± 0.02, P < 0.001, versus wild-type septic mice). Leukocyte adhesion and vascular leakage were discordant in this setting. The finding that septic iNOS-deficient mice exhibited less microvascular leakage than wild-type septic mice despite equivalent increases in leukocyte adhesion suggests an important role for nitric oxide in modulating vascular permeability during sepsis.
登录
查看更多内容
影响因子：
8.8
作者：
GOMEZJIMENEZ, J;SALGADO, A;MONCADA, S
通讯作者：
MONCADA, S
影响因子：
2.1
作者：
Hofstetter, C.;Boost, K. A.;Zwissler, B.
通讯作者：
Zwissler, B.
影响因子：
20.1
作者：
KUROSE, I;KUBES, P;GRANGER, DN
通讯作者：
GRANGER, DN
影响因子：
168.9
作者：
Annane, D;Sanquer, S;Bellissant, E
通讯作者：
Bellissant, E
DOI：
10.1073/pnas.88.11.4651
发表时间：
1991-06-01
影响因子：
11.1
作者：
KUBES, P;SUZUKI, M;GRANGER, DN
通讯作者：
GRANGER, DN