Chemokine RANTES in severe pulmonary arterial hypertension
Chemokine RANTES in severe pulmonary arterial hypertension
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DOI：
10.1164/rccm.2012112
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发表时间：
2002-02-15
影响因子：
24.7
通讯作者：
Humbert, M
中科院分区：
文献类型：
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作者：
Dorfmüller, P;Zarka, V;Humbert, M
近年来发现，散发性和家族性原发性肺动脉高压可能与转化生长因子β家族受体成员编码基因的种系突变有关，这使肺血管疾病中的细胞因子和生长因子引起了人们的广泛关注。在严重的肺动脉高压中已经证明了几种细胞因子的产生，强调了炎症机制在这种情况下的可能影响。此外，在原发性肺动脉高压的丛状病变中检测到由巨噬细胞和淋巴细胞组成的血管周围炎性细胞浸润。趋化因子RANTES是单核细胞和T细胞的重要趋化因子。因此，我们假设趋化因子RANTES促进了重度肺动脉高压患者肺部细胞的募集。逆转录聚合酶链反应显示，RANTES mRNA表达升高，在10例肺样本与严重肺动脉高压患者，与7个对照组相比。原位杂交和免疫组化证实内皮细胞是患者肺动脉壁内RANTES的主要来源。连续切片分析显示RANTES表达与CD45+炎性细胞浸润有关。这些结果支持炎症机制在肺动脉高压的自然史中发挥作用的概念。
The recent discovery that sporadic and familial primary pulmonary hypertension can be associated with germline mutations of genes encoding receptor members of the transforming growth factor-beta family has focused much attention on cytokines and growth factors in pulmonary vascular disorders. Production of several cytokines has been demonstrated in severe pulmonary arterial hypertension, emphasizing the possible influence of inflammatory mechanisms in this condition. Moreover, perivascular inflammatory cell infiltrates composed of macrophages and lymphocytes have been detected in plexiform lesions of primary pulmonary hypertension. Chemokine RANTES is an important chemoattractant for monocytes and T cells. We therefore hypothesize that chemokine RANTES promotes cell recruitment in the lungs of patients displaying severe pulmonary arterial hypertension. Reverse transcriptase polymerase chain reaction demonstrated elevated RANTES mRNA expression in 10 lung samples from patients with severe pulmonary arterial hypertension, as compared with seven control subjects. In situ hybridization and immunohistochemistry confirmed that endothelial cells were the major source of RANTES within the pulmonary artery wall of the patients. Serial sections analysis showed that RANTES expression was associated with CD45+ inflammatory cell infiltrates. These results support the concept that inflammatory mechanisms play a role in the natural history of pulmonary arterial hypertension.