Classically and alternatively activated macrophages contribute to tissue remodelling after myocardial infarction.
Classically and alternatively activated macrophages contribute to tissue remodelling after myocardial infarction.
复制标题
DOI：
10.1111/j.1582-4934.2009.00707.x
复制
发表时间：
2009-09
影响因子：
5.3
通讯作者：
Elsässer A
中科院分区：
文献类型：
--
作者：
Troidl C;Möllmann H;Nef H;Masseli F;Voss S;Szardien S;Willmer M;Rolf A;Rixe J;Troidl K;Kostin S;Hamm C;Elsässer A
心脏病学的一个重要目标是尽量减少心肌坏死，并支持心肌梗死（MI）后离散但有弹性的疤痕形成。巨噬细胞是一种影响心肌梗死期间心脏重构的细胞。因此，本研究的目的是研究它们的转录谱，并确定疤痕组织形成过程中的激活类型。结扎小鼠左冠状动脉前降支。5天后用磁性细胞分选法从梗死组织中分离巨噬细胞。对巨噬细胞的总RNA进行微阵列分析，并与MI和lv对照组的RNA进行比较。在心肌梗死后2、5和10天，通过实时荧光定量PCR （qRT-PCR）验证相关靶点的mRNA丰度。采用免疫组化方法定位激活型特异性蛋白。基因组扫描显示心肌梗死后巨噬细胞主要表达68个靶点，这些靶点中，与经典（肿瘤坏死因子α、白细胞介素6、白细胞介素1β）和替代（精氨酸酶1和2、甘露糖受体C型1、几次质酶3样3）激活的巨噬细胞表型相关的基因mRNA丰度增加，qRT-PCR证实了这一观察结果。通过免疫组织化学，我们证实肿瘤坏死因子α，代表经典激活，在结扎后（2天）早期强烈转录。5 d和10 d后下降。心肌梗死5天后，我们发现巨噬细胞的选择性活化发生了根本性的变化，精氨酸酶1的表达上调。我们的研究结果表明，在心肌梗死后疤痕组织形成的不同阶段，巨噬细胞的活化是不同的。在早期炎症阶段，巨噬细胞主要是经典活化的，而在从炎症到疤痕组织形成到交替活化类型的重要转变过程中，它们的表型发生了变化。
An important goal in cardiology is to minimize myocardial necrosis and to support a discrete but resilient scar formation after myocardial infarction (MI). Macrophages are a type of cells that influence cardiac remodelling during MI. Therefore, the goal of the present study was to investigate their transcriptional profile and to identify the type of activation during scar tissue formation. Ligature of the left anterior descending coronary artery was performed in mice. Macrophages were isolated from infarcted tissue using magnetic cell sorting after 5 days. The total RNA of macrophages was subjected to microarray analysis and compared with RNA from MI and LV-control. mRNA abundance of relevant targets was validated by quantitative real-time PCR 2, 5 and 10 days after MI (qRT-PCR). Immunohistochemistry was performed to localize activation type-specific proteins. The genome scan revealed 68 targets predominantly expressed by macrophages after MI. Among these targets, an increased mRNA abundance of genes, involved in both the classically (tumour necrosis factor α, interleukin 6, interleukin 1β) and the alternatively (arginase 1 and 2, mannose receptor C type 1, chitinase 3-like 3) activated phenotype of macrophages, was found 5 days after MI. This observation was confirmed by qRT-PCR. Using immunohistochemistry, we confirmed that tumour necrosis factor α, representing the classical activation, is strongly transcribed early after ligature (2 days). It was decreased after 5 and 10 days. Five days after MI, we found a fundamental change towards alternative activation of macrophages with up-regulation of arginase 1. Our results demonstrate that macrophages are differentially activated during different phases of scar tissue formation after MI. During the early inflammatory phase, macrophages are predominantly classically activated, whereas their phenotype changes during the important transition from inflammation to scar tissue formation into an alternatively activated type.