Role of Interleukin-1&bgr; in Acute Inflammation and Graft Death After Cell Transplantation to the Heart
Role of Interleukin-1&bgr; in Acute Inflammation and Graft Death After Cell Transplantation to the Heart
复制标题
IL-1 的作用
作者：
Ken Suzuki;B. Murtuza;J. Beauchamp;N. Brand;P. Barton;A. Varela‐Carver;S. Fukushima;S. Coppen;T. Partridge;M. Yacoub
移植细胞存活率低是阻碍细胞移植治疗效果的主要因素；然而，细胞死亡的原因仍不清楚。我们假设白细胞介素-1；（IL-1&bgr;）可能在细胞移植后的急性炎症反应和移植物死亡中起作用，抑制IL-1&bgr；可能会提高移植物的存活率。方法与结果：采用直接肌内注射的方法，将14c标记的雄性骨骼肌前体细胞植入雌性小鼠心脏。14c标记的数量提供了存活细胞数量的估计，而聚合酶链反应测量的男性特异性Smcy基因的数量表示供体来源细胞的总数（存活+增殖）。移植后10分钟，移植细胞存活率为44.8±2.4%，24小时后稳定下降至14.6±1.1%，72小时后下降至7.9±0.6%（每个点n=6）。存活细胞在24 h后开始增殖，细胞总数从24 h时的15.5±0.8%增加到72 h时的24.4±1.6%。急性炎症在24小时突出，72小时减轻，与IL-1&bgr；表达式。抗il -1&bgr；抗体可提高24（25.6±1.6%）和72小时（14.8±1.1%）的移植物存活率，使72小时总细胞数增加2倍（45.8±2.4%）。IL-1&bgr的作用；抑制作用与炎症反应的减少相对应。Conclusion-IL-1&bgr;参与直接心肌细胞移植后的急性炎症和移植物死亡。靶向抑制IL-1&bgr；可能是提高移植物存活率的有效策略。
Background—Poor survival of grafted cells is a major factor hindering the therapeutic effect of cell transplantation; however, the causes of cell death remain unclear. We hypothesized that interleukin-1&bgr; (IL-1&bgr;) might play a role in the acute inflammatory response and graft death after cell transplantation and that inhibition of IL-1&bgr; might improve graft survival. Methods and Results—14C-labeled male skeletal muscle precursor cells were implanted into female mouse hearts by direct intramuscular injection. The amount of 14C-label provides an estimate of the surviving cell number, whereas the amount of male-specific Smcy gene measured by polymerase chain reaction indicates the total (surviving+proliferated) number of donor-derived cells. At 10 minutes after implantation, 44.8±2.4% of the grafted cells survived and this steadily decreased to 14.6±1.1% by 24 hours, and to 7.9±0.6% by 72 hours (n=6 in each point). Proliferation of the surviving cells, which began after 24 hours, resulted in an increase in the total cell number from 15.5±0.8% at 24 hours to 24.4±1.6% at 72 hours. Acute inflammation was prominent at 24 hours and was reduced by 72 hours, in parallel with IL-1&bgr; expression. Administration of anti–IL-1&bgr; antibody improved graft survival at both 24 (25.6±1.6%) and 72 hours (14.8±1.1%) and resulted in a 2-fold increase in the total cell number at 72 hours (45.8±2.4%). The effects of IL-1&bgr; inhibition corresponded with a reduced inflammatory response. Conclusion—IL-1&bgr; is involved in acute inflammation and graft death after direct intramyocardial cell transplantation. Targeted inhibition of IL-1&bgr; may be a useful strategy to improve graft survival.
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影响因子：
20.1
作者：
Douglas J. Ing;Jie Zang;Victor J. Dzau;Keith A. Webster;N. Bishopric
通讯作者：
Douglas J. Ing;Jie Zang;Victor J. Dzau;Keith A. Webster;N. Bishopric
影响因子：
37.8
作者：
Reinecke, H;Zhang, M;Murry, CE
通讯作者：
Murry, CE
影响因子：
5
作者：
Frangogiannis, NG;Youker, KA;Entman, ML
通讯作者：
Entman, ML
影响因子：
15.9
作者：
Murry, CE;Wiseman, RW;Hauschka, SD
通讯作者：
Hauschka, SD