Upregulation of lung chemokines associated with hemorrhage is reversed with a small molecule multiple selectin inhibitor.
Upregulation of lung chemokines associated with hemorrhage is reversed with a small molecule multiple selectin inhibitor.
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小分子多重选择素抑制剂可逆转与出血相关的肺趋化因子的上调。
DOI：
10.1016/s1072-7515(99)00213-6
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发表时间：
1999
影响因子：
5.2
通讯作者：
Ward,PA
中科院分区：
文献类型：
--
作者：
Ramos-Kelly,JR;Toledo-Pereyra,LH;Jordan,JA;Rivera-Chavez,FA;Dixon,RA;Ward,PA
背景：出血可以改变白细胞-内皮细胞反应，导致组织损伤。粘附分子和趋化因子的选择素家族介导白细胞-内皮细胞相互作用，导致中性粒细胞隔离和活化。这项工作研究是否选择素的小分子抑制剂可以改善出血对趋化因子表达和中性粒细胞浸润的影响。我们还旨在评估这种小分子选择素抑制剂在肺功能和结构反应的动物进行出血性shock.Study设计：我们进行了36 Sprague-Dawley大鼠不受控制的出血性休克的一段时间为150分钟的调节作用。包括三组动物（每组n = 12）-假手术组、对照组和治疗组，后者接受25 mg/kg的小分子选择素抑制剂（TBC-1269），其在尾动脉横断后给予。观察复苏150 min时的液体需要量、6 h时的PO2/FiO2比值、肺含水量、肺组织学、肺髓过氧化物酶、肺巨噬细胞炎性蛋白2（MIP 2）mRNA和细胞因子诱导的中性粒细胞趋化因子mRNA。结果：治疗组治疗后肺功能指标（PO2/FiO2比值、肺湿/干水比值）均有明显改善。三组之间的液体需求没有显著变化。通过组织髓过氧化物酶测量，治疗动物的肺中的神经元浸润显著减少（p <0.05）。治疗组的肺组织学显著改善。小分子选择素抑制剂有一个深刻的下调巨噬细胞炎性蛋白-2和尼古丁诱导的中性粒细胞趋化因子在肺tissue.Conclusions表达的影响：我们的研究证实了选择素在失血性休克的发病机制中发挥的关键作用。多选择素阻滞剂允许更好的肺功能和结构。其保护机制可能是通过下调趋化因子的表达和中性粒细胞的浸润。
Background: Hemorrhage can modify the leukocyte–endothelial cell response leading to tissue injury. The selectin family of adhesion molecules and chemokines mediate the leukocyte–endothelial cell interaction, resulting in neutrophil sequestration and activation. This work studies whether a small molecule inhibitor of selectins can ameliorate the effect of hemorrhage on chemokine expression and neutrophil infiltration in the lung. We also aimed to assess the regulatory effect of this small molecule inhibitor of selectins in the lung functional and structural response of animals subjected to hemorrhagic shock.Study Design: We subjected 36 Sprague-Dawley rats to uncontrolled hemorrhagic shock for a period of 150 minutes. Three groups of animals were included (n= 12 per group)—the sham, control, and treated groups, with the latter receiving a small molecule selectin inhibitor (TBC-1269) at 25 mg/kg, which was given after tail artery transection. The following measurements were evaluated: fluid requirements during resuscitation for 150 minutes; PO 2/FiO 2 ratio, lung water, and lung histology, lung myeloperoxidase and lung macrophage inflammatory protein-2 (MIP-2) mRNA and cytokine induced neutrophil chemoattractant mRNA at 6 hours. Statistical analysis included Student’s t-test and ANOVA.Results: There was significant improvement in lung function as expressed by PO 2/FiO 2 ratio and wet to dry lung water ratio in the treated group. There were no significant changes in fluid requirements between the three groups. Neutrophil infiltration, measured by tissue myeloperoxidase, was significantly (p< 0.05) decreased in the lungs of the treated animals. Lung histology was considerably improved in the treated group. The small molecule selectin inhibitor had a profound downregulating effect on macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant as expressed in lung tissue.Conclusions: Our study confirms the key role that selectins play in the pathogenesis of hemorrhagic shock. The multiple selectin blockade allowed for better function and structure of the lung. The mechanism of protection may be secondary to the downregulation of chemokine expression and neutrophil infiltration.
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影响因子：
5.2
作者：
Anaya-Prado, R;Toledo-Pereyra, LH;Ward, PA
通讯作者：
Ward, PA
大鼠失血性休克引起的肺血管损伤是由 P-选择素介导的。
影响因子：
7.5
作者：
Shigeki Kushimoto;K. Okajima;M. Uchiba;K. Murakami;Hiroaki Okabe;Kiyoshi Takatsuki
通讯作者：
Kiyoshi Takatsuki
IgG 免疫复合物诱导的肺损伤中对 C-X-C 趋化因子（巨噬细胞炎症蛋白 2 和细胞因子诱导的中性粒细胞趋化剂）的需求。
DOI：
--
发表时间：
1997
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Shanley,TP;Schmal,H;Warner,RL;Schmid,E;Friedl,HP;Ward,PA
通讯作者：
Ward,PA
P-选择素单克隆抗体可改善兔子失血性休克相关损伤。
DOI：
10.1152/ajpheart.1994.267.6.h2391
发表时间：
1994
期刊：
The American journal of physiology
影响因子：
--
作者：
Winn,RK;Paulson,JC;Harlan,JM
通讯作者：
Harlan,JM
中性粒细胞在失血性休克引起的大鼠胃粘膜损伤中的作用。
影响因子：
29.4
作者：
Smith,SM;Holm-Rutili,L;Perry,MA;Grisham,MB;Arfors,KE;Granger,DN;Kvietys,PR
通讯作者：
Kvietys,PR