Lehmann M H, Kühnert H, Müller S, Sigusch H H
Department of Internal Medicine, Division of Cardiology, University of Jena, Jena, Germany.
Cytokine. 1998 Oct;10(10):739-46. doi: 10.1006/cyto.1998.0354.
The cytotoxic action of leukocytes may be a most probable cause of cardiac myocyte damage seen in chronic myocarditis and dilated cardiomyopathy (DCM). The migration and tissue infiltration of leukocytes is regulated by chemotactic cytokines. Recently, the presence of monocyte chemoattractant protein 1 (MCP-1) messenger RNA has been demonstrated in endomyocardial biopsy tissue obtained from patients with DCM. This chemokine could contribute to enhanced leukocyte recruitment and activation resulting in chronic damage of cardiomyocytes. Accordingly, we sought to determine whether the severity of left ventricular dysfunction in DCM is associated with quantitative alterations of MCP-1 messenger RNA and MCP-1 protein in endomyocardial biopsy tissue. A group of DCM patients with low to moderate impairment of left ventricular function (ejection fraction 45.3+/-2.3%, n=7) was compared to patients with severe left ventricular dysfunction (ejection fraction 25.5+/-3.1%, n=7). MCP-1 messenger RNA expression was determined by quantitative polymerase chain reaction. MCP-1 protein and the presence of infiltrating inflammatory cells were detected by immunohistochemistry. DCM patients with severe left ventricular dysfunction showed a 2.35 fold higher MCP-1 messenger RNA expression when compared to DCM patients with less severe dysfunction (P=0.0229). Positive immunohistochemical staining for MCP-1 was found in all seven patients with severe left ventricular dysfunction and was particularly distinct within the cardiac interstitum. In five of seven patients with less severe systolic dysfunction, MCP-1 protein was found, but was less pronounced and distributed in patchy interstitial areas, close to intramyocardial vessels. Furthermore, there was a consistent trend toward a higher infiltration of inflammatory cells in DCM patients with lower ejection fraction. In conclusion, MCP-1 is dynamically regulated in DCM related deterioration of left ventricular function. This mechanism might contribute to myocyte damage via infiltrated and activated monocytes.
白细胞的细胞毒性作用很可能是慢性心肌炎和扩张型心肌病（DCM）中心肌细胞损伤的一个主要原因。白细胞的迁移和组织浸润受趋化细胞因子调节。最近，在DCM患者的心内膜活检组织中已证实存在单核细胞趋化蛋白1（MCP-1）信使核糖核酸。这种趋化因子可能有助于增强白细胞募集和激活，从而导致心肌细胞的慢性损伤。因此，我们试图确定DCM患者左心室功能障碍的严重程度是否与心内膜活检组织中MCP-1信使核糖核酸和MCP-1蛋白的定量改变有关。将一组左心室功能轻度至中度受损的DCM患者（射血分数45.3±2.3%，n = 7）与严重左心室功能障碍患者（射血分数25.5±3.1%，n = 7）进行比较。通过定量聚合酶链反应测定MCP-1信使核糖核酸表达。通过免疫组织化学检测MCP-1蛋白和浸润性炎症细胞的存在。与左心室功能障碍较轻的DCM患者相比，严重左心室功能障碍的DCM患者MCP-1信使核糖核酸表达高2.35倍（P = 0.0229）。在所有7例严重左心室功能障碍患者中均发现MCP-1免疫组织化学染色阳性，且在心脏间质中尤为明显。在7例收缩功能障碍较轻的患者中，有5例发现了MCP-1蛋白，但不那么明显，分布在靠近心肌内血管的散在间质区域。此外，射血分数较低的DCM患者炎症细胞浸润有持续升高的趋势。总之，MCP-1在DCM相关的左心室功能恶化中受到动态调节。这种机制可能通过浸润和激活的单核细胞导致心肌细胞损伤。
