GAMMA-INTERFERON REGULATES VASCULAR SMOOTH-MUSCLE PROLIFERATION AND IA-ANTIGEN EXPRESSION INVIVO AND INVITRO
GAMMA-INTERFERON REGULATES VASCULAR SMOOTH-MUSCLE PROLIFERATION AND IA-ANTIGEN EXPRESSION INVIVO AND INVITRO
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DOI：
10.1161/01.res.63.4.712
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发表时间：
1988-10-01
影响因子：
20.1
通讯作者：
CLOWES, AW
中科院分区：
文献类型：
--
作者：
HANSSON, GK;JONASSON, L;CLOWES, AW
动脉粥样硬化斑块和损伤引起的内膜增厚中很大一部分动脉平滑肌细胞表达 II 类主要组织相容性复合物 (Ia) 抗原。这可能是这些病变中也存在的 T 淋巴细胞分泌γ-干扰素的结果。因此，我们分析了γ-干扰素对培养的大鼠主动脉平滑肌细胞的影响。重组γ-干扰素在体外抑制平滑肌增殖，呈剂量反应关系；浓度低至 1 单位/ml 时可检测到抑制作用。在相似的浓度下，γ-干扰素也诱导细胞表达 Ia。这表明 Ia 抗原可能由非增殖平滑肌细胞选择性表达。在体内，球囊导管损伤引起的内膜增厚中，Ia 表达与平滑肌细胞的 3H-胸苷标记之间存在很强的负相关。在损伤后连续输注 3H-胸苷两周的大鼠中，Ia 阳性的 3H 阳性细胞比 Ia 阴性的细胞经历了更少的复制轮数。这表明体内和体外 Ia 表达均与增殖能力降低相关。这些结果表明，γ-干扰素（活化的 T 淋巴细胞的分泌产物）在损伤引起的内膜增厚和动脉粥样硬化斑块中充当平滑肌细胞生长和 Ia 表达的天然调节剂。
A significant fraction of the arterial smooth muscle cells in atherosclerotic plaques and injury-induced intimal thickenings express class II major histocompatibility complex (Ia) antigens. This might be the consequence of gamma-interferon secretion by T lymphocytes also present in these lesions. We have therefore analyzed the effects of gamma-interferon on cultured rat aortic smooth muscle cells. Recombinant gamma-interferon inhibited smooth muscle proliferation in vitro in a dose-response relation; inhibition was detectable down to a concentration of 1 unit/ml. In similar concentrations, gamma-interferon also induced Ia expression by the cells. This suggested that Ia antigens might be selectively expressed by nonproliferating smooth muscle cells. In vivo, there was a strong negative correlation between Ia expression and 3H-thymidine labeling of smooth muscle cells in intimal thickenings induced by balloon catheter injury. In rats receiving continuous infusions of 3H-thymidine for two weeks after injury, Ia-positive 3H-positive cells had undergone fewer rounds of replication than Ia-negative ones. This indicates that Ia-expression both in vivo and in vitro is associated with a reduced proliferative capacity. These results suggest that gamma-interferon, a secretory product of activated T lymphocytes, acts as a natural regulator of smooth muscle cell growth and Ia expression in injury-induced intimal thickenings and atherosclerotic plaques.