Ferns G A, Reidy M A, Ross R
Department of Pathology, University of Washington, Seattle 98195.
Am J Pathol. 1991 Apr;138(4):1045-57.
The development of an intimal proliferative lesion after balloon catheter de-endothelialization was studied in congenitally athymic nude rats lacking T lymphocytes. Significant intimal thickening was observed in both the homozygous (nu/nu) and euthymic heterozygous (nu/+) animals 6 days after injury, which increased further after 10 days. There was no significant difference in mean intimal:medial cross-sectional area between the nu/nu and nu/+ animals at either time. Approximately 1% of the cells in the neointima of both groups of animals were leukocytes (OX-1 positive); 0.7% were macrophages (ED-1 positive). In neither nu/nu nor nu/+ animals did T lymphocytes (OX-19-positive cells) constitute more than 0.1% of the neointimal cell population. These data suggest that T lymphocytes do not play a significant role in the accumulation of neointimal cells. The presence of macrophages within the lesions raises the possibility that they may be involved in the recruitment and proliferation of smooth muscle cells. In vitro characterization of nu/nu carotid medial smooth muscle cells demonstrated approximately 500,000 binding sites for platelet-derived growth factor (PDGF)-BB and few PDGF-AA binding sites (less than 10,000). The mitogenic and chemotactic responses of these cells to the three dimeric forms of PDGF correlated with this receptor subunit distribution. Platelet-derived growth factor accounted for approximately 50% of the mitogenic activity of a rat platelet releasate. Platelet-derived growth factor-BB and PDGF-AB were both potent chemotactic agents for the nude rat carotid smooth muscle cells with a peak response at approximately 10 ng/ml. In contrast, PDGF-AA, transforming growth factor beta, and basic fibroblast growth factor were only weak chemoattractants for these cells.
在缺乏T淋巴细胞的先天性无胸腺裸鼠中,研究了球囊导管去内皮化后内膜增生性病变的发展。在损伤后6天,纯合子(nu/nu)和有胸腺杂合子(nu/+)动物均观察到明显的内膜增厚,10天后进一步增加。在这两个时间点,nu/nu和nu/+动物之间的平均内膜:中膜横截面积没有显著差异。两组动物新生内膜中约1%的细胞为白细胞(OX-1阳性);0.7%为巨噬细胞(ED-1阳性)。在nu/nu和nu/+动物中,T淋巴细胞(OX-19阳性细胞)在新生内膜细胞群体中所占比例均不超过0.1%。这些数据表明,T淋巴细胞在新生内膜细胞的积累中不发挥重要作用。病变内巨噬细胞的存在增加了它们可能参与平滑肌细胞募集和增殖的可能性。对nu/nu颈动脉中膜平滑肌细胞的体外特性分析表明,其血小板衍生生长因子(PDGF)-BB的结合位点约为500,000个,而PDGF-AA的结合位点很少(少于10,000个)。这些细胞对三种二聚体形式的PDGF的促有丝分裂和趋化反应与这种受体亚基分布相关。血小板衍生生长因子约占大鼠血小板释放物促有丝分裂活性的50%。血小板衍生生长因子-BB和PDGF-AB对裸鼠颈动脉平滑肌细胞都是有效的趋化剂,在约10 ng/ml时达到峰值反应。相比之下,PDGF-AA、转化生长因子β和碱性成纤维细胞生长因子对这些细胞只是弱趋化剂。