Barnum Scott R, Ames Robert S, Maycox Peter R, Hadingham Sarah J, Meakin Jackie, Harrison David, Parsons Andrew A
Department of Microbiology, University of Alabama, Birmingham, 35294, USA.
Glia. 2002 Apr 15;38(2):169-73. doi: 10.1002/glia.10069.
The receptors for the complement anaphylatoxins C3a and C5a are expressed by glial cells and neurons in normal and inflamed brain. Previous studies demonstrated modest elevations in mRNA expression of these receptors in a model of focal cerebral ischemia. Using a similar model system for both mice and rats, we report markedly different patterns of anaphylatoxin receptor mRNA expression in cerebral ischemia. C5a receptor expression was dramatically elevated within 3 h after middle cerebral artery occlusion, while C3aR expression was reduced to 25% of control animals. By 24 h post-occlusion, expression of both receptors was higher than at any other time point examined. This increased expression at late time points after occlusion is most likely the result of massive infiltration of leukocytes expressing the receptors. We also observed increased receptor mRNA expression in sham-operated animals, indicating that the procedures used for arterial occlusion affects mechanisms regulating receptor expression. This latter result highlights the importance of including this important control group in ischemic model systems for proper interpretation of changes in gene expression.
补体过敏毒素C3a和C5a的受体在正常和发炎的大脑中的神经胶质细胞和神经元中均有表达。先前的研究表明,在局灶性脑缺血模型中,这些受体的mRNA表达有适度升高。使用针对小鼠和大鼠的类似模型系统,我们报告了脑缺血中过敏毒素受体mRNA表达的明显不同模式。大脑中动脉闭塞后3小时内,C5a受体表达急剧升高,而C3aR表达降至对照动物的25%。闭塞后24小时,两种受体的表达均高于其他任何检测时间点。闭塞后晚期时间点的这种表达增加很可能是表达这些受体的白细胞大量浸润的结果。我们还在假手术动物中观察到受体mRNA表达增加,这表明用于动脉闭塞的操作会影响调节受体表达的机制。后一个结果突出了在缺血模型系统中纳入这一重要对照组以正确解释基因表达变化的重要性。