豚鼠前列腺Cajal间质细胞的超微结构特点及功能

目的:观察豚鼠前列腺Cajal间质细胞(interstitial cells of Cajal,ICCs)的超微结构特点以及ICCs和前列腺神经及平滑肌细胞之间的超微结构联系。方法:制作豚鼠前列腺组织切片并进行免疫荧光染色,使用酪氨酸激酶受体(c-Kit)抗体标记ICCs。制作豚鼠前列腺超薄组织切片,在透射电镜下寻找ICCs并观察其超微结构特点以及与周围神经、平滑肌细胞之间的超微结构联系。结果:免疫荧光标记发现豚鼠前列腺间质内有较多的c-Kit阳性ICCs。电镜下发现豚鼠前列腺组织内存在和c-Kit阳性ICCs形态、分布一致,符合典型胃肠道ICCs超微结构特点的间质细胞,这些前列腺ICCs分布于平滑肌细胞之间,与相邻的神经末梢形成典型的突触样连接,和周围的平滑肌细胞之间紧密相连。结论:豚鼠前列腺ICCs具有介导前列腺神经信号,调控平滑肌活动的超微形态学基础。     

远细胞:概念、形态、分布和生理作用

远细胞(telocyte,TC)是近年来新发现并命名的一种间质细胞,因其与Cajal间质细胞(interstitial cells of Cajal,ICC)形态相似,曾被称为Cajal样间质细胞(interstitial Cajal-like cells,ICLC).TC独特的突起结构被称为远足(telopodes),远足很细且极其长,呈念珠形.现已发现,多种形态学及免疫组化染色可以观察或标记远细胞.TC存在于人体内的多种空腔及实质性器官,如心脏、胃肠道、乳腺肺和支气管等.TC因其分布、存在的位置及独有的结构,目前推测其可能具有机械支持、引导组织形成与修复、参与细胞的再生与更新、免疫监视、神经传递等生理作用.     

全层铺片技术显示胃肠道不同部位Cajal间质细胞

正Cajal间质细胞(interstitial cells of Cajal,ICC),是西班牙神经解剖学家Santiago Ramony Cajal于1893年首次在胃肠道中发现的一类特殊间质细胞,与胃肠道平滑肌和神经纤维末梢在解剖学上有紧密联系,具有独立功能,既是胃肠起搏细胞,又具有传导神经递质的作用~[1]。ICC广泛存在于哺乳动物的整个消化道管壁内,按分布区域可大致分为:分布于胃、小肠和结肠内的环肌与纵行肌之间的肌间神经丛ICC;位于黏膜下环肌层表面的ICC;位于小肠深肌丛区域的ICC;广泛散布于环肌和纵肌肌束内的ICC~[2]。目前消化道全层铺片技术由于能够直观、全面地显示ICC的分布、形态以及形成的细胞网络,而成为研究胃肠神经系统的重要方法之一,但文献中却鲜少提及此方法的详细操作过程。已知ICC特异性表达由原癌基因c-kit编码的受体酪氨酸激酶     

2.108 糖尿病大鼠模型胃Cajal间质细胞、平滑肌细胞、神经和血管的超微结构研究

目的观察糖尿病大鼠模型胃Cajal间质细胞、平滑肌细胞、神经和血管的超微结构改变,为糖尿病性胃轻瘫的发生提供理论依据.方法健康成年雄性SD大鼠50只,体重250～300g,随机分为2组.糖尿病组 30只;正常对照组20只.糖尿病组实验大鼠先稳定3天,然后给予禁食12h(晚8时至早 8时),自由饮水,晨8时大鼠乙醚麻醉后,糖尿病组给予四氧嘧啶45mg/kg经舌下静脉1次注射,饲养4个月,定期测定血糖浓度≥200mg/mL,同时尿糖在以上确定为糖尿病模型.正常对照组对照组给予等量生理盐水注射.大鼠颈椎脱位后,剖腹迅速剪取胃,沿胃小弯侧剖开胃,在装有Kreb's液的烧杯内仔细去除胃肠内容物,Kreb's液的组成为120.3NaCl,5 .9KCl,2.5CaCl2,1.2MgCl2,20.2NaHCO3,1.2NaH2PO4,11.5glucose.取胃底、胃体、胃窦组织各1块,并将组织平铺于滤纸上,2.5%戊二醛固定后,0.1mol/L的磷酸缓冲液冲洗,1%的四氧化饿后固定,0.1mol/L的磷酸缓冲液冲洗,乙醇梯度脱水,Epo n 812浸透包埋,半超薄切片1～2μm,染色后光镜下定位,确认粘膜层、粘膜下层、环形肌层和纵行肌层的位置.用瑞典LKB超薄切片机行超薄切片50nm,超薄切片用酒精醋酸双氧铀、再用柠檬酸铅染色,用HITACHI H-600透射电镜观察照相.结果糖尿病大鼠模型胃Cajal间质细胞数量减少.Cajal间质细胞超微结构的变化为Cajal间质细胞与其它的Cajal间质细胞之间、与平滑肌细胞之间、与神经末梢之间的连接显著减少,尚存的细胞间连接的结构也有破坏、结构不清,连接松散,线粒体肿胀、空泡样变、甚至溶解,细胞内的胞质广泛溶解,有大量的胞质内空泡形成,Cajal间质细胞内的细胞器数量较正常减少,核糖体减少,粗面内质网脱颗粒,核内异染色质明显.糖尿病大鼠模型胃平滑肌细胞排列紊乱,肌细胞内有很多较大的胞质溶解性空泡,线粒体肿胀、空泡样变、溶解.糖尿病大鼠模型胃神经末梢部分肿胀、溶解,肌间丛神经元的细胞核溶解坏死,胞质部分溶解,线粒体肿胀,嵴溶解,粗面内质网扩张,质部分溶解.糖尿病大鼠模型胃毛细血管管壁显著不平,管壁增厚、淤曲,连续性中断,胞质内有小空泡.结论糖尿病大鼠模型胃Cajal间质细胞、平滑肌细胞、神经和血管的超微结构改变,可能是胃肠功能紊乱--胃轻瘫的发生的病理基础.     

消化管壁的超微结构及Cajal细胞的形态特征

胃肠道蠕动运动和心脏相似 ,具有自动节律性。它主要受四种因素的调节 :肠道神经系统 ,平滑肌本身 ,体液调节和 Cajal细胞。前三者和其他脏器的神经及体液调节大同小异 ,惟有 Cajal细胞为胃肠道所特有。Cajal细胞是西班牙著名神经解剖学家 Cajal应用镀银染色技术 ,在胃肠道壁内所描述的一种特殊细胞 ;它主要分布于肌间神经丛周围和深肌丛附近。对于它的形态、生物学特性、超微结构及其功能等 ,研究者之间意见分歧较大。 80年代初 ,丹麦学者 Thuneberg提出它可能具有Pacemaking activity,从而掀起了对 Cajal细胞的研究热潮。我们利用传统…     

大白鼠海马神经毯内神经胶质突起与神经无突起间关系的超微结构研究

用电镜技术观察了大白鼠海马神经毯内的神经胶质突起与神经元突起的超微结构。本文论述了星状胶质细胞突起与神经元的树突、树突侧棘和轴突膜间联系的超微形态特点，发现星状胶质细胞突起广泛分布于神经毯内，与神经元突起间形成膜的紧密并列关系，但不形成突触，也未见二膜间并列处有膜的增厚和突触小泡聚集的现象。星状胶质细胞突起上的棘状突起的超微结构特征不同于树突的侧棘，无棘器的构造。首次发现有的神经胶质棘状突起上有小棘结构。有些棘状突起借粘着斑与树突形成细胞间连接。     

肠道间质细胞与肠道疾病

肠道间质细胞 (interstitalcellofCajal,ICC)是一类既不同于典型的平滑肌细胞 ,也不同于雪旺氏细胞的胃肠道的间质细胞 ,该细胞是 1893年西班牙神经解剖学家SantiagoRamonCajal首先对此类细胞作了详细的描述。后人称之为Cajal(卡哈尔 )细胞。多年来一直未引起人们的重视 ,近年来随着研究的不断深入 ,对其来源及功能有了进一步的认识 ,并发现此细胞与许多胃肠道疾病及肿瘤的发生有关。一、ICC的形态和分布在肠道的肠壁 ,有一种间质细胞穿插在平滑肌组织内 ,包绕Auerbush神经丛形成细胞网络 ,这种细胞叫ICC。近 2 0年引起科学家的重视。…     

胃肠道间质瘤的电镜和免疫组织化学研究

目的 探讨胃肠道间质瘤的组织起源和神经分化特征。方法 应用电镜和免疫组织化学对20例胃肠道间质瘤的超微结构和神经分化相关抗原表达进行研究。结果 20例胃肠道间质瘤c—kit表达均阳性。其中7例超微结构存在神经分化,12例未见神经或肌细胞分化,仅有1例存在向平滑肌纤维分化。神经分化形态表现为瘤细胞胞质和胞质突起内可见散在或簇状分布的致密核心颗粒,并形成突触样结构。并可见神经元样突起、饮液空泡和团丝样纤维。神经分化伴有致密核心颗粒病例在良性、交界性和恶性组各有1例、1例和5例。神经分化组病例神经分化相关抗原神经元特异性烯醇化菌、CD99、S—100和CD56阳性表达分别有7例、7例、5例和4例,均高于未定分化组。结论 胃肠道间质瘤和所谓的胃肠道自主神经肿瘤在组织形态和免疫表型都存在相互重叠现象,神经分化超微结构观察和神经分化相关抗原分析有助于确定胃肠道间质瘤的神经分化改变以及潜在的生物学行为。     

胃肠道间质瘤起源和分化的探讨

目的 探讨胃肠道间质瘤(GIST)的起源或分化。方法 采用免疫组织化学EnVision和电镜的方法对GIST进行研究。结果 212例GIST CD117、CD34、α—平滑肌肌动蛋白(SMA)、肌特异性肌动蛋白、结蛋白阳性率分别为96．7％,77．3％,19．3％,15．6％,1．9％,其中S—100和PGP9．5的阳性反应分别为16．3％及12．3％。超微结构显示瘤细胞含丰富的线粒体,粗面内质网、游离核糖体和中间丝,有的细胞切面可见溶酶体和脂滴,高尔基复合体在核周分布,质膜处偶尔不规则地分布着一些微饮泡、密斑样结构及不连续的基板。部分病例细胞有多量细长指状突起,突起内有胞内成分如线粒体、粗面内质网延续,突起之间或突起与细胞膜有连接结构。细胞外间质内可见胶原原纤维或团丝样纤维。结论 GIST免疫表型及超微结构特征与胃肠壁成熟卡哈尔间质细胞相似,提示GIST可能是起源于幼稚间充质细胞向卡哈尔间质细胞分化的肿瘤,并具有一定的肌性特征。     

大白鼠海马神经毯内神经胶质突起与神经元突起间关系的超微结构…

用电镜技术观察了大白鼠海马神经毯内的神经胶质突起与神经元突起的超微结构。本文论述了星状胶质细胞突起与神经元的树突、树突侧棘和轴突膜间联系的超微形态特点，发现星状胶质细胞突起广泛分布于神经毯内，与神经元突起间形成膜的紧密并列关系，但不形成突触，也未见二膜间并列处有膜的增厚和突触小泡聚集的现象。星状胶质细胞突起上的棘状突起的超微结构特征不同于树突的侧棘，无棘器的构造。产次发现有的神经胶质棘状突起上有小     

Muscarinic M(2) acetylcholine receptor distribution in the guinea-pig gastrointestinal tract

In the enteric nervous system, acetylcholine is the most common neurotransmitter to induce gastrointestinal smooth muscle contractions. Cholinergic signaling is mediated by muscarinic acetylcholine receptors on the surface of smooth muscle cells. Five different muscarinic receptor subtypes (M(1)-M(5)) have been identified and characterized, all of which belong to the superfamily of the G-protein-coupled receptor. The muscarinic M(2) acetylcholine receptor is the major muscarinic receptor subtype expressed by smooth muscle tissues in the gastrointestinal tract, where it is coexpressed with a smaller population of M(3) receptor. In this study, we examined the immunohistochemical distribution of the M(2) receptor using a specific antibody in the guinea-pig gastrointestinal tract. M(2) receptor-like immunoreactivity was mainly observed as associated with smooth muscle cells in the gastrointestinal tract. M(2) receptor-like immunoreactivity in smooth muscle cells was distributed throughout the cell membrane associated with caveolae. In the proximal colon, M(2) receptor-like immunoreactivity in the smooth muscle cells was weak. In the small intestine, interstitial cells of Cajal that possessed neurokinin 1 receptor-like immunoreactivity had intense M(2) receptor-like immunoreactivity. In the proximal colon, intramuscular and myenteric interstitial cells of Cajal exhibited M(2) receptor-like immunoreactivity. These findings indicate that, in the gastrointestinal musculature, M(2) receptors are distributed both in the smooth muscle cells and interstitial cells of Cajal, suggesting that the M(2) receptor elicits smooth muscle cell contraction and the interstitial cells of Cajal are the sites of innervation by enteric cholinergic neurons.     

Gastrointestinal pacemaker cell tumor: clinicopathological, immunohistochemical, and ultrastructural study with special reference to c-kit receptor antibody

Recent studies indicate that a subgroup of gastrointestinal stromal tumors, including gastrointestinal autonomic nerve tumors (GANTs), originate from stem cells that differentiate toward a pacemaker-cell phenotype. These pacemaker cells form a complex network intercalated between the autonomic nerves and the muscle walls of the gastrointestinal tract and are called interstitial cells of Cajal (ICC). The c-kit receptor (CD117) is a sensitive marker for ICC. The aim of our study was to support the hypothesis that GANTs show ICC differentiation. Seven GANTs without convincing smooth muscle or neural differentiation all showed homogeneous reactivity for the c-kit receptor. CD34 was positive in three cases. On electron microscopy, the typical features of GANT were present. Six tumors contained skeinoid fibers. Most tumors were related to the small bowel. They presented as single (two cases) or multiple (five cases) tumors. The presenting symptoms were abdominal bleeding (2), abdominal mass (2), anemia (1), and small-bowel perforation (1). In two cases, liver metastases developed. Because of the close immunohistochemical and electron microscopic similarities of these tumors to the interstitial cells of Cajal, the term gastrointestinal pacemaker cell tumor seems appropriate. Received: 31 May 1999 / Accepted: 19 October 1999     

消化道蠕动的起搏器与Cajal间质细胞

消化道蠕动是消化道平滑肌群的节律性收缩活动。越来越多的研究证据表明,这种活动是由一类叫做(pacem aker)起搏器的特殊细胞引起的。这些细胞可能就是分布在消化道平滑肌层间的(interstitialcells of Cajal)ICC。它们因分布的部位不同而形态各异。但它们都含有丰富的线粒体,呈c-K it免疫染色阳性,并伸出很多突起形成网络。他们相互之间及与周围的平滑肌细胞之间以缝隙结合相连接。这篇综述主要介绍此类细胞的形态结构及分布特点。     

Selective double staining of interstitial cells of Cajal and macrophage-like cells in small intestine by an improved supravital methylene blue technique combined with FITC-dextran uptake

Summary By a brief exposure of small intestine (mouse, rat, guinea pig) to lysolecithin prior to vital methylene blue staining we were able to demonstrate in a selective way the complete network of interstitial cells of Cajal, located in the space between the longitudinal and circular muscle layers. A combination with fluorescence labeling (FITC-dextran uptake) of macrophage-like cells, allowed us to demonstrate 1) the complete, regular distribution of both cell populations along the entire small intestine, and 2) the constant, intimate associations between interstitial cells of Cajal and macrophage-like cells.In relation to current hypotheses concerning a role of interstitial cells of Cajal in motility regulation, our results call attention to the possible involvement of another cell type, the macrophage-like cell.A preliminary account of this study was published in the proc. of The XIth Symp. Gastrointest. Motil., Oxford, 1987, in: Digest. Dis. Sci. 32:922     

Mesenchymal tumors of the gastrointestinal tract: a paradise for acronyms (STUMP, GIST, GANT, and now GIPACT), implication of c-kit in genesis, and yet another of the many emerging roles of the interstitial cell of Cajal in the pathogenesis of gastrointestinal diseases?

This commentary addresses the nature of interstitial cells of Cajal (which can now be conveniently demonstrated by immunostaining for c-kit) and their possible role in the genesis of various motility disorders of the gastrointestinal tract. The evolution of the concept on the nature of gastrointestinal stromal tumors is discussed, with emphasis on the recent finding of a very high frequency of c-kit immunoreactivity in these tumors, suggesting that they might exhibit differentiation toward interstitial cells of Cajal. The practical immunohistochemical applications of antibodies to c-kit in diagnostic pathology are also discussed.     

Clinicopathologic and immunohistochemical characteristics of upper gastrointestinal leiomyomas harboring interstitial cells of Cajal: A potential mimicker of gastrointestinal stromal tumor

ObjectiveTo analyze clinicopathologic characteristics of upper gastrointestinal leiomyomas and to determine the distribution and immunohistochemical features of interstitial cells of Cajal, in order to designate whether they can cause diagnostic challenges.Materials and methodsTwenty-four upper gastrointestinal leiomyomas (14 esophagus, 10 stomach) were retrieved. CD117, DOG-1 and muscle markers were performed. The staining was analyzed based on the distribution and percentage. Interstitial cells of Cajal were distinguished based on their positivity for both CD117 and DOG-1 immunohistochemistry, along with their morphological features.ResultsMean age of patients was 49 years, M/F ratio was 2.4. Patients with gastric leiomyomas were significantly younger than those with esophageal leiomyomas (41.5 vs. 54.3, p = 0.012). Histologically, leiomyomas were similar to their endometrial counterpart. Immunohistochemically, all tumors had strong/diffuse positivity for muscle markers. CD117 highlighted mast cells in all cases. Three cases had prominently increased mast cells. Both CD117 and DOG-1 also highlighted interstitial cells of Cajal in 24/24 (100%) of cases. Interstitial cells of Cajal were distributed in variable proportions, from focal to homogenous. In one case, they constituted 50% of tumor cells. In 16 cases, the distribution was homogenous. Superficial leiomyomas (n = 3) had only focal CD117 and DOG-1 positivity.ConclusionUpper gastrointestinal leiomyomas harbor expression of CD117 and DOG-1 in entrapped/colonized interstitial cells of Cajal, which can cause a potential pitfall in the differential diagnosis, especially in cases that show prominent immunohistochemical positivity. Evaluation of the immunohistochemistry can be exceptionally challenging in small biopsy/cytology specimens. Careful histologic evaluation of the tumor as well as the recognition of interstitial cells of Cajal will help the pathologist render the accurate diagnosis.     

Ultrastructural studies of gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract (GIT). Although interstitial cells of Cajal has been suggested as origin of this tumor, the cytological and ultrastructural features of GISTs are heterogeneous and unclear. A total 10 cases of normal gastrointestinal tissue (control), 13 GISTs of the stomach (8), small intestine (3), mesocolon (1) and liver (1), and 2 gastrointestinal autonomic nervous tumor (GANT) of small intestine were ultrastructurally studied. Normal interstitial cells of Cajal (ICC) were abundantly present around the myenteric plexuses or individually scattered through the wall of GIT. ICC was characterized by slender cytoplasmic processes, well-developed endoplasmic reticulum (ER), mitochondria, Golgi apparatus, caveolae and intermediate filaments. The GISTs and GANTs had overlapping ultrastructures. The most common and important ultrastructural features of GISTs were rich villous cytoplasmic processes, dispersed intermediate filaments and abundant SER, and those of GANTs were neurosecretory granules and skenoid fibers. Compared with ICC, the GISTs and GANTs had remarkably reduced caveolae and gap junctions. Our study suggested that ultrastructural analysis gives much information to investigate lineage differentiation of neoplastic cells and make a differential diagnosis of these tumors from other mesenchymal tumors and between GISTs and GANTs.     

长爪沙鼠胃肠道Cajal间质细胞的形态学

目的 探讨长爪沙鼠胃肠道Cajal间质细胞（ICCs）的形态和分布规律。 方法 采用10只成年长爪沙鼠,体重50~70g,取胃、小肠、结肠制作冷冻切片,结合全层铺片的c-Kit免疫荧光染色。结果 ICCs呈网络状分布于整个胃肠道,不同部位ICCs的分布及形态有所不同。在胃底部,仅见肌内ICCs(ICC-IM）,而在胃体和胃窦部除ICC-IM外,可见肌间ICCs(ICC-MY)分布在肌间神经丛周围;其细胞密度胃底ICC-IM最多,由胃底至胃窦逐渐减少,而ICC-MY由胃体至胃窦逐渐增多。在小肠可见ICC-IM, ICC-MY和深肌层ICCs(ICC-DMP)3个亚群,结肠管壁内也分布有ICC-IM、ICC-MY和黏膜下ICCs(ICC-SM)3个亚群。结论 沙鼠可用于有关ICCs正常形态、结构及功能的研究。     

Interstitial cells: involvement in rhythmicity and neural control of gut smooth muscle

Many smooth muscles display spontaneous electrical and mechanical activity, which persists in the absence of any stimulation. In the past this has been attributed largely to the properties of the smooth muscle cells. Now it appears that in several organs, particularly in the gastrointestinal tract, activity in smooth muscles arises from a separate group of cells, known as interstitial cells of Cajal (ICC), which are distributed amongst the smooth muscle cells. Thus in the gastrointestinal tract, a network of interstitial cells, usually located near the myenteric plexus, generates pacemaker potentials that are conducted passively into the adjacent muscle layers where they produce rhythmical membrane potential changes. The mechanical activity of most smooth muscle cells, can be altered by autonomic, or enteric, nerves innervating them. Previously it was thought that neuroeffector transmission occurred simply because neurally released transmitters acted on smooth muscle cells. However, in several, but not all, regions of the gastrointestinal tract, it appears that nerve terminals, rather than communicating directly with smooth muscle cells, preferentially form synapses with ICC and these relay information to neighbouring smooth muscle cells. Thus a set of ICC, which are distributed amongst the smooth muscle cells of the gut, are the targets of transmitters released by intrinsic enteric excitatory and inhibitory nerve terminals: in some regions of the gastrointestinal tract, the same set of ICC also augment the waves of depolarisation generated by pacemaker ICC. Similarly in the urethra, ICC, distributed amongst the smooth muscle cells, generate rhythmic activity and also appear to be the targets of autonomic nerve terminals.     

Intestitial cells of Cajal in the human small intestine: immunochemical and ultrastructural study

The stem cell kinase CD117 has recently been found to play an important role in the development of interstitial cells of Cajal (ICC), which are currently regarded as pacemaker cells of the gastrointestinal tract. CD117 is expressed in both gastrointestinal stromal tumors (GIST) and ICC, with the latter regarded by many as the progenitor cells of GIST. The authors investigated immunoreactivity of 25 normal surgically removed small intestinal tissues and correlated the findings with electron microscopy (EM) on 12 cases. In all cases CD117-positive cells were frequently seen around the myenteric plexi either singly or in groups. CD117-positive cells on immunostained sections corresponded to the cells appearing as fibroblast-like or undifferentiated primitive mesenchymal cells around the myenteric ganglia and interstitial spaces by EM. In contrast, S-100 stain revealed a fine network of positive staining throughout the muscularis. Branches of nonmyelinated axons and nerve endings were found regularly between myocytes with direct contact with muscle cells by EM. The cells that we could depict as ICC because of their distribution andstaining pattern of CD117 were limited to the nonmuscular mesenchymal cells. No muscle cell-like ICC were found. Instead, the muscle cells in direct contact with nerve endings were often disfigured and the cytoarchitectural contents for muscle cells became less distinct because of lighter staining and loss of definite focal densities among actin filaments. However, these latter cells did maintain most muscle cell features, such as continuous external lamina, caveolae, and some of the peripheral densities. These findings raise a possibility that previous investigators could have included these altered muscle cells into the ICC group. It was also found that intestinal muscularis not only was richly endowed with an elaborate neural network of delicate axonal extensions and dense-core granule containing nerve endings traversing through and between myocytes, but also showed frequent synapse-like direct contact between nerve endings and muscle cells. These findings indicate that enteric nerves may play a major role in the control of intestinal motility, while CD117-positive cells play an accessory role as cells of Cajal as originally speculated. Further studies are necessary to better define and characterize interstitial cells of Cajal, which will be useful in the correlation of the vast number of data concerning the possible role of CD117-positive ICC in the pacemaker function of the intestine and oncogenesis of GIST.