Division of Cardiology, Department of Translational Pathophysiological Research, University of Antwerp, Wilrijk, Belgium.
Pathology. 2011 Apr;43(3):239-47. doi: 10.1097/PAT.0b013e328344e266.
Previously we demonstrated decreased blood myeloid (m) and plasmacytoid (p) dendritic cell (DC) counts in atherosclerotic patients. Therefore, we examined whether DCs, in particular DC precursors, accumulate in human plaques.
Blood DC antigen (BDCA)-1, CD11c (mDCs), BDCA-2, CD123 (pDCs), langerin, fascin, S-100 (immature/mature DCs), and CD1a and CD83 (mature DCs) were investigated by immunohistochemistry of carotid arteries obtained by endarterectomy (EAS, frozen n = 11, fixed n = 11) or autopsy (fixed, n = 87).
Fascin and S-100 required formaldehyde fixation, other markers needed cryo-preservation. BDCA-1, BDCA-2, langerin, and S-100 appeared specific for intimal DCs, unlike CD123 and fascin (staining endothelial cells), CD11c and CD1a (staining monocytes, foam cells) or CD83 (staining lymphocytes). BDCA-1 and BDCA-2 cells were detected in EAS, preferentially near microvessels. S-100 cells increased successively from intimal thickening, via pathological intimal thickening, fibrous cap atheroma and finally complicated plaques. Fascin cells followed the same pattern, but were more abundant. However, in lesions containing microvessels (complicated plaques, plaque shoulders and most EAS) this was partly explained by fascin positive endothelial cells. Even complicated plaques contained relatively few mature CD83 DCs.
Accumulation of BDCA-1 and BDCA-2 around neovessels showed that mDCs and pDCs are recruited to advanced plaques, which is in line with the previously described decline of circulating blood DCs in patients with coronary artery disease. Unexpectedly, several DC markers yielded false positive signals. Hence, some accounts on numbers, trafficking and activation of DCs in atherosclerotic plaques may require re-evaluation.
此前我们发现动脉粥样硬化患者血液中髓系(m)和浆细胞样(p)树突状细胞(DC)计数减少。因此，我们研究了 DC 特别是 DC 前体细胞是否在人类斑块中聚集。
采用免疫组织化学法检测颈动脉内膜切除术(EAS，冰冻 n=11，固定 n=11)或尸检(固定，n=87)获得的动脉标本中血 DC 抗原(BDCA)-1、CD11c(mDCs)、BDCA-2、CD123(pDCs)、朗格汉斯、 fascin、S-100(未成熟/成熟 DCs)、CD1a 和 CD83(mature DCs)。
fascin 和 S-100 需要甲醛固定，其他标记物需要冷冻保存。BDCA-1、BDCA-2、朗格汉斯和 S-100 似乎是内皮层 DC 的特异性标记物，而 CD123 和 fascin(染色内皮细胞)、CD11c 和 CD1a(染色单核细胞、泡沫细胞)或 CD83(染色淋巴细胞)则不是。BDCA-1 和 BDCA-2 细胞在 EAS 中被检测到，主要存在于微脉管附近。S-100 细胞从内膜增厚、病理性内膜增厚、纤维帽粥样硬化瘤，最后到复杂斑块，其数量逐渐增加。fascin 细胞也呈现出相同的模式，但更为丰富。然而，在含有微血管的病变(复杂斑块、斑块肩部和大多数 EAS)中，这部分是由 fascin 阳性内皮细胞解释的。即使是复杂斑块，也只含有相对较少的成熟 CD83 DC。
BDCA-1 和 BDCA-2 围绕新血管的聚集表明 mDCs 和 pDCs 被募集到晚期斑块中，这与之前描述的冠心病患者循环血液 DC 减少是一致的。出乎意料的是，一些 DC 标记物产生了假阳性信号。因此，一些关于动脉粥样硬化斑块中 DC 数量、迁移和激活的报道可能需要重新评估。
