CD133与实体肿瘤预后的研究进展

CD133是一种公认的肿瘤干细胞新型标记物,在多种肿瘤组织中表达.不同类型肿瘤中,CD133的表达对于预后的影响不同,在直肠癌、脑肿瘤和乳腺癌中CD133的表达与预后差相关,而在肺癌、肝癌、胰腺癌和黑色素瘤中CD133的表达与预后的关系尚存在争议.扩大样本量、准确评估CD133的表达与肿瘤预后的关系,将为肿瘤患者治疗的选择和疗效评估提供帮助,CD133有望成为多种肿瘤预后评估的广谱有效标记物.     

单核细胞CD36表达与强直性脊柱炎

背景：强直性脊柱炎是一种涉及到慢性全身炎症的自身免疫性疾病,肿瘤坏死因子和白细胞介素6在强直性脊柱炎患者中升高,而肿瘤坏死因子和白细胞介素6等炎症因子可以抑制CD36在单核细胞的表达。 目的：分析单核细胞CD36的表达与强直性脊柱炎的关系。 方法：纳入84例初诊为强直性脊柱炎的患者和111例健康对照人群,应用流式细胞学技术检测强直性脊柱炎患者和健康人群单核细胞CD36的表达情况,同时,检测两组的生物化学、免疫学、血液常规以及相关炎症因子等指标。 结果与结论：两组受试者基本资料比较结果显示,强直性脊柱炎患者单核细胞CD36荧光强度低于健康对照人群(P < 0.01)。单核细胞CD36荧光强度水平与C-反应蛋白、血沉、白细胞介素6以及肿瘤坏死因子负相关。另外,单核细胞CD36荧光强度水平与BASDAI评分呈负相关。Logistic回归分析结果显示,血沉、肿瘤坏死因子、白细胞介素6以及单核细胞CD36荧光强度与强直性脊柱炎相关,为强直性脊柱炎患者的危险因素(P < 0.05)。结果提示,强直性脊柱炎释放的炎症因子可以下调单核细胞CD36的表达,单核细胞CD36低表达与在强直性脊柱炎存在联系。在临床上,检测单核细胞CD36的表达可能可以作为判断强直性脊柱炎患者机体炎症反应程度和疾病活动性有效的指标。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

CD69与免疫功能的调节

CD69是一种Ⅱ型跨膜糖蛋白,属于C-型凝集素受体家族,也是NK细胞信号传导基因复合体家族的一员.CD69最早是在激活的淋巴细胞上被发现并加以描述,后来发现经诱导后它几乎可在所有的血细胞上表达.虽然CD69的生理性配体还未明确,但与CD69交联可产生细胞内信号传导及多种免疫反应,并对造血细胞的生物学功能有广泛的作用.而且研究发现CD69与血液系统疾病及免疫相关性疾病的发病机理有关.本文就CD69的结构、基因定位与调节,在不同细胞上的表达与功能以及CD69与疾病的关系作一综述.     

应用PCR-SBT方法检测CD36相关基因变异的研究

CD36为一种血小板上的特异性抗原，又称glycoprotein Ⅳ(GPⅣ)，是血小板反应(thrombospondin)受体[1]。CD36基因变异会导致CD36抗原的缺失，此类人群若有输血、怀孕、造血干细胞移植等免疫因素就可能产生anti-CD36抗体[2-3]，导致血小板输注无效，输血后紫斑，各种免疫性血小板减少等临床症状；另外也有研究指出CD36基因变异与高血脂症、感染疟疾及胰岛素耐受性有关联[4]；近来在CD36基因剔除的小鼠中研究发现，血小板可经由CD36接受微颗粒(microparticles)的刺激而活化，CD36缺乏血小板被微颗粒活化的能力会降低，因而使止血时间延长[5]。     

CD69与免疫功能的调节

CD69是一种Ⅱ型跨膜糖蛋白。属于G型凝集素受体家族，也是NK细胞信号传导基因复合体家族的一员。CD69最早是在激活的淋巴细胞上被发现并加以描述，后来发现经诱导后它几乎可在所有的血细胞上表达。虽然CD69的生理性配体还未明确，但与CD69交联可产生细胞内信号传导及多种免疫反应，并对造血细胞的生物学功能有广泛的作用。而且研究发现CD69与血液系统疾病及免疫相关性疾病的发病机理有关。本文就CD69的结构、基因定位与调节，在不同细胞上的表达与功能以及CD69与疾病的关系作一综述。     

单核细胞与内皮细胞的相互作用对单核细胞CD36表达的影响

目的:研究单核细胞、内皮细胞的相互作用对单核细胞清道夫受体CD36抗原表达的影响并在此基础上观察细胞因子在其中的介导作用。方法:使用单核细胞、内皮细胞单独培养及混合培养的方法形成不同的培养条件,通过ABC-ELISA法检测培养液中巨噬细胞集落刺激因子(M-CSF)的含量,使用流式细胞术检测单核细胞表面CD36抗原的表达程度。结果:单核细胞单独培养条件下CD36的表达量较低,在和内皮细胞混合培养后CD36表达量显著升高(P＜0.05),M-CSF和血小板源性生长因子(PDGF-BB)在单核细胞CD36表达增高的调节中起着一定的介导作用,但不占主要地位。结论:单核细胞与内皮细胞的相互作用可通过多种环节上调单核细胞CD36的表达,从而参与动脉粥样硬化的发展。     

广州地区无偿献血者CD36基因突变的频率调查

目的:本研究旨在调查广州地区无偿献血者中CD36基因的突变频率,填补国内CD36抗原缺失相关的基因突变空白。方法:收集200份健康无偿献血员的血液标本,通过PCR-SSP的方法检测广州地区CD36抗原缺失相关的基因突变频率,统计分析并对比国外报道。结果:在200份血液标本中,一共检测出10个样本产生CD36的基因突变,突变类型、例数和频率分别为:C268T,1例,0.5%;329-330delAC,6例,3.0%;A1237C,3例,1.5%。结论:本课题首次利用PCR-SSP方法检测广州地区无偿献血者CD36基因的突变频率,发现主要突变类型为329-330delAC,其次是A1237C,这与国外报道的主要突变类型,C268T,329-330delAC和949insA有所不同。     

表达人CD36基因的293T细胞株的建立

目的 建立一种表达人类CD36基因的293T细胞株,用于CD36抗原的研究及CD36抗体检测.方法 采用RT-PCR技术,从人血小板中获取CD36基因的cDNA,克隆至表达载体pEGFP-C1中,对重组质粒测序鉴定后将质粒转染至293T细胞,该转基因的产物在293T细胞中的表达被观察超过1年.与CD36单克隆抗体及CD36阳性血清反应的流式细胞术试验评估这个细胞株的敏感性和特异性.结果 重组表达载体pEGFP-C1-CD36被成功构建,流式细胞术验证其转染效率达90％以上,实时荧光定量PCR和Western blot证明CD36基因在293T细胞中过表达.流式细胞试验结果为CD36单克隆抗体及CD36阳性血清为阳性,而其他所有的血清样本,包括CD36抗体阴性血清、含有HLA或HPA-3a抗体血清均为阴性.结论 建立的pEGFP-C1-CD36-293T细胞株能成功高效表达CD36抗原,并能特异快速、成功地检测CD36抗体,并且不受其他血型抗体的干扰,有一定的运用前景.     

重视CD30在淋巴瘤病理诊断中的检测与评估

CD30是肿瘤坏死因子受体家族中的一种跨膜糖蛋白, 在多种淋巴瘤中具有不同程度的表达, 对肿瘤细胞增殖和功能有特异性影响。然而, 临床和病理医师尚未充分认识其表达意义, 且CD30的检测与评估也未形成规范。因此, 本文就CD30在淋巴瘤诊断中的作用、检测方法与报告标准等方面进行概述, 以提高对CD30的认识。     

单核细胞表面CD86分子的研究进展

共刺激分子在抗原递呈中起着重要的作用,CD86则是非常重要的共刺激分子,它与配体CD28和CTLA-4相结合后,能够产生重要的免疫学效应.CD86的升高和降低受多种因素影响.CD86的升高与降低在临床上也具有重要的意义,并且和疾病的预后相关.对于自身免疫性疾病而言,对CD86信号的调节,也提供了合理的有效的调节免疫系统的途径.     

CD36, a class B scavenger receptor, is expressed on microglia in Alzheimer's disease brains and can mediate production of reactive oxygen species in response to beta-amyloid fibrils.

A pathological hallmark of Alzheimer's disease is the senile plaque, composed of beta-amyloid fibrils, microglia, astrocytes, and dystrophic neurites. We reported previously that class A scavenger receptors mediate adhesion of microglia and macrophages to beta-amyloid fibrils and oxidized low-density lipoprotein (oxLDL)-coated surfaces. We also showed that CD36, a class B scavenger receptor and an oxLDL receptor, promotes H(2)O(2) secretion by macrophages adherent to oxLDL-coated surfaces. Whether CD36 is expressed on microglia, and whether it plays a role in secretion of H(2)O(2) by microglia interacting with fibrillar beta-amyloid is not known. Using fluorescence-activated cell sorting analysis and immunohistochemistry, we found that CD36 is expressed on human fetal microglia, and N9-immortalized mouse microglia. We also found that CD36 is expressed on microglia and on vascular endothelial cells in the brains of Alzheimer's disease patients. Bowes human melanoma cells, which normally do not express CD36, gained the ability to specifically bind to surfaces coated with fibrillar beta-amyloid when transfected with a cDNA encoding human CD36, suggesting that CD36 is a receptor for fibrillar beta-amyloid. Furthermore, two different monoclonal antibodies to CD36 inhibited H(2)O(2) production by N9 microglia and human macrophages adherent to fibrillar beta-amyloid by approximately 50%. Our data identify a role for CD36 in fibrillar beta-amyloid-induced H(2)O(2) production by microglia, and imply that CD36 can mediate binding to fibrillar beta-amyloid. We propose that similar to their role in the interaction of macrophages with oxLDL, class A scavenger receptors and CD36 play complimentary roles in the interactions of microglia with fibrillar beta-amyloid.     

CD36 as a lipid sensor

CD36 is a multifunctional protein homologous to the class B scavenger receptor SR-B1 mainly found in tissues with a sustained lipid metabolism and in several hematopoieic cells. CD36 is thought to be involved in various physiological and pathological processes like angiogenesis, thrombosis, atherogenesis, Alzheimer's disease or malaria. An additive emerging function for CD36 is a role as a lipid sensor. Location of CD36 and orthologue molecules in plasma membrane of cells in contact with the external environment (e.g. gustatory, intestinal or olfactory epithelia) allows the binding of exogenous-derived ligands including dietary lipids, diglycerides from bacterial wall in mammals and even a lipid-like pheromone in insects. Similar function might also exist in the brain in which a CD36-dependent sensing of fatty acids has been reported in ventromedial hypothalamic neurons in rodents. Specific recognition of lipid-related molecules by a receptor-like protein highly conserved throughout the evolution strongly suggests that lipid-sensing by CD36 is responsible for basic physiological functions in relation with behavior, energy balance and innate immunity.     

OxLDL or TLR2-induced cytokine response is enhanced by oxLDL-independent novel domain on mouse CD36

OxLDL binding to CD36 is shown to result in macrophage activation and foam cell formation that have been implicated in atherosclerosis. However, CD36 has also been shown to induce inflammatory response to other ligands besides oxLDL. During the course of blocking CD36 oxLDL binding function using anti CD36 antibodies, we have identified a novel domain of CD36 that triggers inflammatory response-independent of oxLDL binding. OxLDL bound to the mouse reporter cell line RAW-Blue induced TNF-α and RANTES mRNA and protein expression. Pretreatment of RAW-Blue cells with an anti-mCD36 mAb, JC63.1, an activating mCD36 mAb, surprisingly did not inhibit oxLDL-induced response. Further, binding of this antibody to CD36 alone induced a pro-inflammatory cytokine response in RAW-Blue cells as well as primary mouse macrophages. The induction of cytokine response was specific only to this antibody and was CD36-dependent, since CD36(-/-) macrophages failed to induce a similar response. The interaction of the antibody to CD36 led to activation of NF-κB and MAP kinase. Notably, a CD36 peptide blocked oxLDL-induced foam cell formation and macrophage activation. However, the activating mCD36 mAb induced macrophage activation was not inhibited by CD36 peptide. Further, activating mCD36 mAb enhanced oxLDL- or TLR2- or TLR4-mediated inflammatory responses. Collectively, our data provide evidence that activating mCD36 mAb binds to a domain different from the oxLDL-binding domain on mouse CD36, and suggest that interaction at this domain may contribute to oxLDL-independent macrophage inflammatory responses that lead to chronic inflammatory diseases.     

beta-Amyloid promotes accumulation of lipid peroxides by inhibiting CD36-mediated clearance of oxidized lipoproteins

BACKGROUND: Recent studies suggest that hypercholesterolemia, an established risk factor for atherosclerosis, is also a risk factor for Alzheimer's disease. The myeloid scavenger receptor CD36 binds oxidized lipoproteins that accumulate with hypercholesterolemia and mediates their clearance from the circulation and peripheral tissues. Recently, we demonstrated that CD36 also binds fibrillar beta-amyloid and initiates a signaling cascade that regulates microglial recruitment and activation. As increased lipoprotein oxidation and accumulation of lipid peroxidation products have been reported in Alzheimer's disease, we investigated whether beta-amyloid altered oxidized lipoprotein clearance via CD36. METHODS: The availability of mice genetically deficient in class A (SRAI & II) and class B (CD36) scavenger receptors has facilitated studies to discriminate their individual actions. Using primary microglia and macrophages, we assessed the impact of Abeta on: (a) cholesterol ester accumulation by GC-MS and neutral lipid staining, (b) binding, uptake and degradation of 125I-labeled oxidized lipoproteins via CD36, SR-A and CD36/SR-A-independent pathways, (c) expression of SR-A and CD36. In addition, using mice with targeted deletions in essential kinases in the CD36-signaling cascade, we investigated whether Abeta-CD36 signaling altered metabolism of oxidized lipoproteins. RESULTS: In primary microglia and macrophages, Abeta inhibited binding, uptake and degradation of oxidized low density lipoprotein (oxLDL) in a dose-dependent manner. While untreated cells accumulated abundant cholesterol ester in the presence of oxLDL, cells treated with Abeta were devoid of cholesterol ester. Pretreatment of cells with Abeta did not affect subsequent degradation of oxidized lipoproteins, indicating that lysosomal accumulation of Abeta did not disrupt this degradation pathway. Using mice with targeted deletions of the scavenger receptors, we demonstrated that Abeta inhibited oxidized lipoprotein binding and its subsequent degradation via CD36, but not SRA, and this was independent of Abeta-CD36-signaling. Furthermore, Abeta treatment decreased CD36, but not SRA, mRNA and protein, thereby reducing cell surface expression of this oxLDL receptor. CONCLUSIONS: Together, these data demonstrate that in the presence of beta-amyloid, CD36-mediated clearance of oxidized lipoproteins is abrogated, which would promote the extracellular accumulation of these pro-inflammatory lipids and perpetuate lipid peroxidation.     

CD36-mediated nonopsonic phagocytosis of erythrocytes infected with stage I and IIA gametocytes of Plasmodium falciparum

Gametocytes, the sexual stages of malaria parasites (Plasmodium spp.) that are transmissible to mosquitoes, have been the focus of much recent research as potential targets for novel drug and vaccine therapies. However, little is known about the host clearance of gametocyte-infected erythrocytes (GEs). Using a number of experimental strategies, we found that the scavenger receptor CD36 mediates the uptake of nonopsonized erythrocytes infected with stage I and IIA gametocytes of Plasmodium falciparum by monocytes and culture-derived macrophages (Mphis). Light microscopy and immunofluorescence assays revealed that stage I and IIA gametocytes were readily internalized by monocytes and Mphis. Pretreating monocytes and Mphis with a monoclonal antibody that blocked CD36 resulted in a significant reduction in phagocytosis, as did treating GEs with low concentrations of trypsin to remove P. falciparum erythrocyte membrane protein 1 (PfEMP-1), a parasite ligand for CD36. Pretreating monocytes and Mphis with peroxisome proliferator-activated receptor gamma-retinoid X receptor agonists, which specifically upregulate CD36, resulted in a significant increase in the phagocytosis of GEs. Murine CD36 on mouse Mphis also mediated the phagocytosis of P. falciparum stage I and IIA gametocytes, as determined by receptor blockade with anti-murine CD36 monoclonal antibodies and the lack of uptake by CD36-null Mphis. These results indicate that phagocytosis of stage I and IIA gametocytes by monocytes and Mphis appears to be mediated to a large extent by the interaction of PfEMP-1 and CD36, suggesting that CD36 may play a role in innate clearance of these early sexual stages.     

Apical CD36 immunolocalization in human and porcine taste buds from circumvallate and foliate papillae

CD36 is the receptor for long chain fatty acids (LCFA), and is expressed in lingual taste cells from rodents. In these animals, CD36 has been proposed to play an important role in oral detection of LCFA, and subsequently, determines their dietary fat preference. Humans also seem to detect LCFA in the oral cavity, however, information on the molecular mechanism of this human orosensory LCFA recognition is currently lacking. The aim of our study was to investigate whether CD36 is also expressed in lingual human and porcine taste buds cells. Using fluorescence immunohistochemistry, apical CD36 expression was revealed in human and porcine taste bud cells from circumvallate and foliate papillae. These data suggest CD36 as the putative orosensory receptor for dietary LCFA in human, and, therefore, may be involved in our preference for fatty foods.     

IL-13 induces expression of CD36 in human monocytes through PPARgamma activation

The class B scavenger receptor CD36 is a component of the pattern recognition receptors on monocytes that recognizes a variety of molecules. CD36 expression in monocytes depends on exposure to soluble mediators. We demonstrate here that CD36 expression is induced in human monocytes following exposure to IL-13, a Th2 cytokine, via the peroxisome proliferator-activated receptor (PPAR)gamma pathway. Induction of CD36 protein was paralleled by an increase in CD36 mRNA. The PPARgamma pathway was demonstrated using transfection of a PPARgamma expression plasmid into the murine macrophage cell line RAW264.7, expressing very low levels of PPARgamma, and in peritoneal macrophages from PPARgamma-conditional null mice. We also show that CD36 induction by IL-13 via PPARgamma is dependent on phospholipase A2 activation and that IL-13 induces the production of endogenous 15-deoxy-Delta12,14-prostaglandin J2, an endogenous PPARgamma ligand, and its nuclear localization in human monocytes. Finally, we demonstrate that CD36 and PPARgamma are involved in IL-13-mediated phagocytosis of Plasmodium falciparum-parasitized erythrocytes. These results reveal a novel role for PPARgamma in the alternative activation of monocytes by IL-13, suggesting that endogenous PPARgamma ligands, produced by phospholipase A2 activation, could contribute to the biochemical and cellular functions of CD36.     

Activation of Rat Alveolar Macrophage-Derived Latent Transforming Growth Factor β-1 by Plasmin Requires Interaction with Thrombospondin-1 and its Cell Surface Receptor, CD36

Transforming growth factor-beta-1 (TGF-beta1) is secreted by cells in a latent form (L-TGF-beta1) noncovalently bound to a latency-associated peptide. Activated alveolar macrophages obtained from rat lungs after bleomycin-induced pulmonary injury released increased amounts of active TGF-beta1 as well as plasmin, a protease, and thrombospondin-1 (TSP-1), a trimeric glycoprotein. Previously we had demonstrated that plasmin was critical to the activation of L-TGF- beta1. In the present study we demonstrated that TSP-1 is also important for the activation of L-TGF- beta1 because the activation can be inhibited by anti-TSP-1 monoclonal antibody. Proteins obtained from alveolar macrophage cell lysates immunoprecipitated with antibodies specific for TSP-1 were identified on immunoblots as LAP and TGF-beta1, indicating that TSP-1/L-TGF-beta1 complexes are present on alveolar macrophages. However, in the presence of plasmin both latency-associated peptide and TGF-beta1 were decreased in the same cell lysates, indicating that L-TGF-beta1 associated with TSP-1 is released by plasmin. Using immunofluorescence and antibodies to TGF-beta1 and CD36, a receptor for TSP-1, there was colocalization of TGF-beta1 with CD36. Because TSP-1 but not TGF-beta1 is a natural ligand for CD36, these findings suggest that the L-TGF-beta1 in a complex with TSP-1 localizes to the macrophage cell surface when TSP-1 interacts with its receptor, CD36. Furthermore, the association of TSP-1/L-TGF-beta1 complex with CD36 is necessary to the activation of L-TGF-beta1 because antibodies to CD36 prevent the colocalization of TGF-beta1 with CD36 as observed by immunofluorescence and inhibit activation of the L-TGF-beta1 by explanted alveolar macrophages. These findings suggest that activation of L-TGF-beta1 by plasmin occurs at the cell surface of activated alveolar macrophages and requires a TSP-1/CD36 interaction.