Frangogiannis N G, Perrard J L, Mendoza L H, Burns A R, Lindsey M L, Ballantyne C M, Michael L H, Smith C W, Entman M L
The Methodist Hospital and The DeBakey Heart Center, Department of Medicine, Baylor College of Medicine, Houston, Tex 77030-3498, USA.
Circulation. 1998 Aug 18;98(7):687-98. doi: 10.1161/01.cir.98.7.687.
Myocardial infarction is associated with an intense inflammatory reaction leading to healing and scar formation. Because mast cells are a significant source of fibrogenic factors, we investigated mast cell accumulation and regulation of stem cell factor (SCF), a potent growth and tactic factor for mast cells, in the healing myocardium.
Using a canine model of myocardial ischemia and reperfusion, we demonstrated a striking increase of mast cell numbers during the healing phase of a myocardial infarction. Mast cell numbers started increasing after 72 hours of reperfusion, showing maximum accumulation in areas of collagen deposition (12.0+/-2.6-fold increase; P<0.01) and proliferating cell nuclear antigen (PCNA) expression. The majority of proliferating cells were identified as alpha-smooth muscle actin-positive myofibroblasts or factor VIII-positive endothelial cells. Mast cells did not appear to proliferate. Using a nuclease protection assay, we demonstrated induction of SCF mRNA within 72 hours of reperfusion. Immunohistochemical studies demonstrated that a subset of macrophages was the source of SCF immunoreactivity in the infarcted myocardium. SCF protein was not found in endothelial cells and myofibroblasts. Intravascular tryptase-positive, FITC-avidin-positive, CD11b-negative mast cell precursors were noted in the area of healing and in the cardiac lymph after 48 to 72 hours of reperfusion.
Mast cells increase in number in areas of collagen deposition and PCNA expression after myocardial ischemia. The data provide evidence of mast cell precursor infiltration into the areas of cellular injury. SCF is induced in a subset of macrophages infiltrating the healing myocardium. We suggest an important role for SCF in promoting chemotaxis and growth of mast cell precursors in the healing heart.
心肌梗死与导致愈合和瘢痕形成的强烈炎症反应相关。由于肥大细胞是促纤维化因子的重要来源，我们研究了愈合心肌中肥大细胞的积聚以及干细胞因子（SCF）的调节情况，SCF是一种对肥大细胞具有强大生长和趋化作用的因子。
使用犬心肌缺血再灌注模型，我们证明在心肌梗死愈合阶段肥大细胞数量显著增加。再灌注72小时后肥大细胞数量开始增加，在胶原沉积区域显示出最大积聚（增加12.0±2.6倍；P<0.01）以及增殖细胞核抗原（PCNA）表达。大多数增殖细胞被鉴定为α平滑肌肌动蛋白阳性的肌成纤维细胞或因子VIII阳性的内皮细胞。肥大细胞似乎未增殖。使用核酸酶保护试验，我们证明再灌注72小时内SCF mRNA被诱导。免疫组织化学研究表明，梗死心肌中SCF免疫反应性的来源是一部分巨噬细胞。在内皮细胞和成纤维细胞中未发现SCF蛋白。再灌注48至72小时后，在愈合区域和心脏淋巴中发现血管内类胰蛋白酶阳性、FITC抗生物素蛋白阳性、CD11b阴性的肥大细胞前体。
心肌缺血后，胶原沉积区域和PCNA表达区域的肥大细胞数量增加。数据提供了肥大细胞前体浸润到细胞损伤区域的证据。SCF在浸润愈合心肌的一部分巨噬细胞中被诱导。我们认为SCF在促进愈合心脏中肥大细胞前体的趋化和生长方面发挥重要作用。
