Miller D D, Craig F E, Dressler F A, Aguirre F V, Farrar M A, Breland C M, Donohue T J, Kern M J, Bach R G
St Louis University Medical Center, Department of Internal Medicine, Missouri 063110-0250, USA.
Coron Artery Dis. 1995 Dec;6(12):965-72.
Prior histologic studies have examined smooth muscle cell, macrophage and thrombus constituents of atherosclerotic coronary atherectomy specimens. Lymphocytes and mononuclear leukocytes are also detectable in atherosclerotic surgical pathology specimens utilizing immunocytochemical techniques.
In order to quantify the histological contribution of cytokine receptor-expressing immunocompetent cells to human coronary artery stenoses, 30 directional atherectomy catheter biopsy specimens (wet weight < or = 10 mg) from 16 patients were snap frozen (-70 degrees C) for quantitative immunocytochemical studies. Following computer-assisted quantification of total intimal nuclei per tissue section (mean 297 +/- 177; cell density 7 +/- 5/10(4) microns 2), monoclonal antibody cytochemistry was used to identify the percentage of these cells expressing antigenic clusters of differentiation (CD) characteristic of T-lymphocytes, B-lymphocytes and monocytes. Identification of alpha (low affinity) and beta (intermediate affinity) interleukin-2 receptors on intimal cells was accomplished using a three-step streptavidin-biotin method.
A significant percentage of intimal cells were of lymphocytic (11 +/- 13%) or monocytic (12 +/- 14%) origin, with helper T-cells (9 +/- 12%) outnumbering both suppressor T-cells (2 +/- 4%) and B-lymphocytes (1 +/- 2%). Interleukin-2 receptors were noted on 9 +/- 12% of intimal cells, including cells with a vascular smooth muscle phenotype.
These quantitative immunocytochemical data conclusively demonstrate that lymphocytes and monocytes account for over 20% of coronary plaque cells obtained by in-vivo atherectomy, and that helper (CD4) T-cells predominate over suppressor (CD8) T-cells and B-lymphocytes. Variable interleukin-2 receptor subtype expression occurs in mononuclear leukocytes infiltrating chronic human atheroma. By applying these techniques, the therapeutic effects of cytotoxic agents on selectively targeted cytokine receptor-expressing cells may now be evaluated in vivo in small human directional coronary atherectomy specimens.
既往组织学研究已对动脉粥样硬化性冠状动脉斑块旋切术标本中的平滑肌细胞、巨噬细胞和血栓成分进行了检测。利用免疫细胞化学技术在动脉粥样硬化手术病理标本中也可检测到淋巴细胞和单核白细胞。
为了量化表达细胞因子受体的免疫活性细胞对人类冠状动脉狭窄的组织学贡献，对16例患者的30份定向斑块旋切导管活检标本（湿重≤10 mg）进行速冻（-70℃）以进行定量免疫细胞化学研究。在计算机辅助定量每个组织切片的内膜细胞核总数（平均297±177；细胞密度7±5/10⁴μm²）后，使用单克隆抗体细胞化学来鉴定这些细胞中表达T淋巴细胞、B淋巴细胞和单核细胞特征性分化抗原簇（CD）的细胞百分比。使用三步链霉亲和素-生物素方法鉴定内膜细胞上的α（低亲和力）和β（中等亲和力）白细胞介素-2受体。
相当比例的内膜细胞起源于淋巴细胞（11±13%）或单核细胞（12±14%），辅助性T细胞（9±12%）的数量超过抑制性T细胞（2±4%）和B淋巴细胞（1±2%）。在9±12%的内膜细胞上发现了白细胞介素-2受体，包括具有血管平滑肌表型的细胞。
这些定量免疫细胞化学数据确凿地表明，淋巴细胞和单核细胞占通过体内斑块旋切术获得的冠状动脉斑块细胞的20%以上，且辅助性（CD4）T细胞多于抑制性（CD8）T细胞和B淋巴细胞。在浸润慢性人类动脉粥样硬化的单核白细胞中存在可变的白细胞介素-2受体亚型表达。通过应用这些技术，现在可以在小型人类定向冠状动脉斑块旋切术标本中体内评估细胞毒性药物对选择性靶向表达细胞因子受体的细胞的治疗效果。
