Hinescu M E, Gherghiceanu Mihaela, Mandache E, Ciontea Sanda M, Popescu L M
Department of Cellular and Molecular Medicine, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
J Cell Mol Med. 2006 Jan-Mar;10(1):243-57. doi: 10.1111/j.1582-4934.2006.tb00306.x.
We have previously reported (Hinescu & Popescu, 2005) the existence of interstitial Cajal-like cells (ICLC), by transmission electron microscopy, in human atrial myocardium. In the present study, ICLC were identified with non-conventional light microscopy (NCLM) on semi-thin sections stained with toluidine blue and immunohistochemistry (IHC) for CD117/c-kit, CD34, vimentin and other additional antigens for differential diagnosis. Quantitatively, on semi-thin sections, ICLC represent about 1-1.5% of the atrial myocardial volume (vs. approximately 45% working myocytes, approximately 2% endothelial cells, 3-4% for other interstitial cells, and the remaining percentage: extracellular matrix). Roughly, there is one ICLC for 8-10 working atrial myocytes in the intercellular space, beneath the epicardium, with a characteristic (pyriform, spindle or triangular) shape. These ICLC usually have 2-3 definitory processes, emerging from cell body, which usually embrace atrial myocytes (260 nm average distance plasmalemma/sarcolemma) or establish close contact with nerve fibers or capillaries (approximately 420 nm average distance to endothelial cells). Cell prolongations are characteristic: very thin (mean thickness = 0.15+/-0.1 microm), very long for a non-nervous cell (several tens of microm) and moniliform (uneven caliber). Stromal synapses between ICLC and other interstitial cells (macrophages) were found (e.g. in a multicontact type synapse, the average synaptic cleft was approximately 65 nm). Naturally, the usual cell organelles (mitochondria, smooth and rough endoplasmic reticulum, intermediate filaments) are relatively well developed. Caveolae were also visible on cell prolongations. No thick filaments were detected. IHC showed that ICLC were slightly and inconsistently positive for CD117/c-kit, variously co-expressed CD34 and EGF receptor, but appeared strongly positive for vimentin, along their prolongations. Some ICLC seemed positive for a-smooth muscle actin and tau protein, but were negative for nestin, desmin, CD13 and S-100. In conclusion, we provide further evidence of the existence of ICLC in human atrial myocardium, supporting the possible ICLC role in pacemaking, secretion (juxta- and/or paracrine), intercellular signaling (neurons and myocytes). For pathology, ICLC might as well be 'players' in arrhythmogenesis and atrial remodeling.
我们之前曾报道过（Hinescu和Popescu，2005年），通过透射电子显微镜观察，在人心房心肌中存在间质 Cajal样细胞（ICLC）。在本研究中，通过对用甲苯胺蓝染色的半薄切片进行非传统光学显微镜（NCLM）观察以及对CD117/c-kit、CD34、波形蛋白和其他用于鉴别诊断的附加抗原进行免疫组织化学（IHC）检测，鉴定出了ICLC。定量分析显示，在半薄切片上，ICLC约占心房心肌体积的1 - 1.5%（相比之下，工作心肌细胞约占45%，内皮细胞约占2%，其他间质细胞占3 - 4%，其余百分比为细胞外基质）。大致而言，在心外膜下方的细胞间隙中，每8 - 10个工作心房肌细胞就有一个ICLC，其具有特征性形状（梨形、梭形或三角形）。这些ICLC通常有2 - 3个明确的突起，从细胞体发出，通常环绕心房肌细胞（质膜/肌膜平均距离为260 nm），或与神经纤维或毛细血管建立紧密接触（与内皮细胞平均距离约为420 nm）。细胞突起具有特征性：非常细（平均厚度 = 0.15±0.1微米），对于非神经细胞来说非常长（几十微米）且呈念珠状（管径不均匀）。发现了ICLC与其他间质细胞（巨噬细胞）之间的基质突触（例如在多接触型突触中，平均突触间隙约为65 nm）。自然地，常见的细胞器（线粒体、滑面和粗面内质网、中间丝）发育相对良好。在细胞突起上也可见小窝。未检测到粗肌丝。免疫组织化学显示，ICLC对CD117/c-kit呈弱阳性且不一致，不同程度地共表达CD34和表皮生长因子受体，但沿其突起对波形蛋白呈强阳性。一些ICLC似乎对α-平滑肌肌动蛋白和tau蛋白呈阳性，但对巢蛋白、结蛋白、CD13和S-100呈阴性。总之，我们提供了更多关于人心房心肌中存在ICLC的证据，支持ICLC在起搏、分泌（旁分泌和/或自分泌）、细胞间信号传导（神经元和心肌细胞）方面可能发挥的作用。对于病理学而言，ICLC也可能是心律失常发生和心房重塑中的“参与者”。
