血管平滑肌细胞粘附分子的表达与心血管疾病的关系

粘附分子是指由细胞合成、存在于细胞膜或细胞外,介导细胞间、细胞与细胞基质粘附的一大类分子。与心血管疾病有关的粘附分子包括整合素家族、免疫球蛋白超家族和选择素家族。免疫球蛋白超家族成员细胞间粘附分子（intercellular adhesion molecule-1,ICAM-1）和血管细胞粘附分子（vascular cell adhesionmolecule-1,VCAM-1）在白细胞向激活的内皮细胞粘附过程中起重要作用。血管内皮细胞表达粘附分子的作用已比较清楚,但几年前有人发现在动脉粥样硬化血管壁的内膜平滑肌细胞也表达ICAM-1和VCAM-1,这就引起了与这些分子相关问题的探讨。本文就ICAM-1和VCAM-1在血管平滑肌细胞表达的调节及在动脉     

血管平滑肌细胞粘附分子的表达与心血管疾病的关系

粘附分子是指由细胞合成、存在于细胞膜或细胞外,介导细胞间、细胞与细胞基质粘附的一大类分子.与心血管疾病有关的粘附分子包括整合素家族、免疫球蛋白超家族和选择素家族.免疫球蛋白超家族成员细胞间粘附分子(intercellular adhesion molecule-1,ICAM-1)和血管细胞粘附分子(vascular cell adhesion molecule-1,VCAM-1)在白细胞向激活的内皮细胞粘附过程中起重要作用.血管内皮细胞表达粘附分子的作用已比较清楚,但几年前有人发现在动脉粥样硬化血管壁的内膜平滑肌细胞也表达ICAM-1和VCAM-1,这就引起了与这些分子相关问题的探讨.本文就ICAM-1和VCAM-1在血管平滑肌细胞表达的调节及在动脉粥样硬化(AS)和血管再狭窄发生、发展中的作用作一综述.     

粘附分子与急性肺损伤

1粘附分子概述细胞粘附分子是一类介导细胞与细胞、细胞与细胞外基质间相互结合的重要活性物质,它在维护正常组织的稳定、介导炎症细胞的迁移、血栓的形成以及肿瘤转移等过程中起重要的作用。它主要包括选择素家族、整合素家族、免疫球蛋白超家族。2细胞粘附分子在急性肺损伤中的作用急性肺损伤(AcuteLungInjury,ALI)是一种失控的炎症反应,以肺血管内皮细胞及肺泡上皮细胞广泛损伤为其病理特征。多形核白细胞于肺内大量“扣押”及其释放各种蛋白酶、氧自由基以及促炎症细胞因子引起组织损伤是导致上述损伤的关键,而粘附分子在此过程中发…     

L-选择素与动脉粥样硬化相关性的研究进展

细胞黏附分子（CAMs）是泛指一类介导细胞与细胞或细胞与细胞基质间相互结合,起黏附作用的糖蛋白,主要位于血管内皮细胞和白细胞表面。黏附分子的种类很多,根据其化学结构和功能特点分为五大类：（1）选择素家族;（2）整合素家族;（3）免疫球蛋白超家族;（4）钙黏附素家族;（5）尚未被归类的细胞黏附分子,如：CD33、CD36等。1983年,     

循环的粘附分子在疾病中

细胞粘附分子是位于细胞膜表面的一类大分子糖蛋白 ,表达于循环白细胞和组织固有细胞表面 ,通过介导细胞与细胞间、细胞与细胞外基质相互粘连 ,从而促使白细胞贴壁、外渗、游走、聚集、抗原表达和淋巴细胞激活 ,细胞粘附分子 -1 (ICAM -1 )、E -选择素分别属于免疫球蛋白基因超家族和选择素家族的一员。一些疾病如糖尿病、AIDS、炎症疾病等可促进I CAM -1和E -选择素在内皮细胞的表达 ,它的表达与随后增强的粘附力功能有关。本文主要通过研究采用ELISA方法检测各种疾病中CAM在血清中的不同水平。迄今已发现的粘附分子有 5类 ,包括…     

粘附分子的研究概况

异物或病原体进入人体，机体免疫细胞通过血管壁移行到周围组织，对外界抗原进行了清除，并对损伤的组织进行修复是生物体维持正常生理平衡的重要功能。粘附分子是介导细胞与细胞之间以臃怀胞外基质间相互结合的细胞表面受体，根据结构和生化性质分为三个超家族，即整合素家族，免疫球蛋白家话和选择素家族。     

粘附分子在炎症疾病中的作用

细胞粘附分子(CAM)在炎症反应中起着关键的作用。选择素(selectins)、整合蛋白(integrins)和免疫球蛋白(Ig)基因超家族粘附受体介导着白细胞自血流向炎症聚集处迁移的不同阶段。激活的内皮细胞可促使细胞粘附分子的表达并触发内皮细胞与白细胞的反应。选择素在白细胞与活性内皮细胞最初的相互作用阶段起效(缠绕或滚动),而整合蛋白和Ig超家族的CAM则使这些细胞的粘附牢固并促使其渗出。在滚动过程中,白细胞则被CAM和化学促活受体产生的细胞内信号激活。因此,阻断CAM的功能或其表达已成为治疗炎症疾病的一个新途径。有多种药物(如阿司     

细胞间粘附分子—1与冠心病

细胞间粘附分子-1(intercellular adhesion molecule-1,ICAM-1)是Rothlein等于1986年在研究淋巴细胞粘附中发现的一种LFA-1的配体,克隆号CD_(54),它是一种单链糖蛋白,属于粘附分子免疫球蛋白基因超家族类。胞外有5个串联的单链免疫球蛋白样结构域,可作为配基与白细胞表面表达的LFA-1(CD_(11a)/CD_(18))和Mac-1(CD_(11b)/CD_(18))分子结合,介导白细胞与血管内皮细胞粘附及白细胞穿出血管壁。     

细胞粘附分子研究和开发的新进展

多种生理过程包括细胞的激活、迁移、增殖、分化以及其它的过程需要细胞之间、细胞与细胞外基质之间的直接接触。细胞与细胞和细胞与细胞外基质之间的相互作用是通过几种不同家族的细胞粘附分子所介导的，它们包括整合素、选择素、钙粘着蛋白和免疫球蛋白。细胞粘附分子的商业和治疗潜力在不断提高，新发现的细胞粘附分子以及某些疾病状态下整合素、选择素、免疫球蛋白新作用的发现为诊断性和治疗性药物的研究和开发提供了很好的机会     

西洛他唑对磷脂多糖诱导的粘附及粘附分子释放的影响

目的　研究磷酸二酯酶 3型抑制剂西洛他唑对磷脂多糖 (LPS)诱导的粘附及血管内皮细胞 (ECs)释放可溶性细胞粘附分子 (sCAMs)的影响。方法　体外培养第 4～ 6代人脐静脉血管内皮细胞 (HUVECs) ,以LPS(5mg·L- 1)刺激 ,并与西洛他唑 (1～ 10 μmol·L- 1)共培养 2 4h ,观察西洛他唑对由LPS诱导的HUVECs与中性粒细胞之间的粘附的影响 ;另取培养上清 ,以ELISA法测定HUVECs释放可溶性血管细胞粘附分子 1(sVCAM 1)、细胞间粘附分子 1(sICAM 1)以及E 选择素 (sE selectin ,sELAM 1)。结果　西洛他唑抑制由LPS诱导的HUVECs与中性粒细胞之间的粘附以及HUVECs释放sVCAM 1,而对sICAM 1和sE 选择素无影响。并且 ,该药对于sVCAM 1的抑制作用被蛋白激酶A(PKA)抑制剂H 89所阻断。结论　西洛他唑对由细胞因子LPS诱导的粘附反应以及ECs释放sVCAM 1有抑制作用 ,后者可能与PKA依赖性通路相关     

Endothelial cell adhesion molecules and cancer progression

The role of cell adhesion molecules (CAMs), such as intercellular cell adhesion molecule-1 (ICAM-1), vascular endothelial cell adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin, has been studied extensively in the process of inflammation. These molecules are responsible for recruiting leukocytes onto the vascular endothelium before extravasation to the injured tissues. Some circulating cancer cells have been shown to extravasate to a secondary site using a process similar to inflammatory cells. The most studied ligands for CAMs expressed on cancer cells, sialyl Lewis (a/x) antigens, are shown to be involved in adhesion to endothelial cells by binding to E-selectin. This process, shared by inflammatory cells and cancer cells, may partially explain the link between inflammation and tumorigenesis. Furthermore, this process may elucidate the therapeutic benefit of anti-inflammatory drugs in cancer treatment. The complexity of the tumor microenvironment has been revealed in the past decade. Currently, intense investigation is aimed at various aspects of the tumor microenvironment in addition to the tumor cells themselves. Here, we review the role of CAMs in extravasation of circulating cancer cells, a key step in metastasis.     

Review. Leukocyte and endothelial cell adhesion molecules in inflammation focusing on inflammatory heart disease

In multicellular organisms the development of adhesion bonds, either among cells or among cells and components of the extracellular matrix, is a crucial process. These interactions are mediated by molecules which are named adhesion molecules and play a main role both at the early stages of the development of tissue integrity and later. Cell adhesion molecules (CAMs) have a key role in several pathologies such as cancer and inflammatory diseases. Selectins, integrins and immunoglobulin gene superfamily of adhesion receptors mediate different steps of leukocyte migration from the bloodstream towards the inflammatory foci. Leukocyte interactions with the vascular endothelium are highly orchestrated processes that include the capture of free-flowing leukocytes from the blood with subsequent leukocyte rolling, arrest, firm adhesion and ensuing diapedesis. These interactions occur under high shear stresses within venules and depend on multiple families of adhesion molecules. As a response to infection mediators, leukocyte gathering is considered to be crucial for the adequate defence of the organism to any kind of injury or infection. Endothelial activation contributes significantly to the systemic inflammatory response to bacteraemia and increased expression. Release of soluble endothelial markers into the circulation has been demonstrated together with elevated plasma levels of CAMs and has been reported in bacteraemic patients. It has been proposed that infection of endothelial cells with Staphylococcus aureus, Streptococcus sanguis, or Staphylococcus epidermidis induces surface expression of ICAM-1 and VCAM-1 and monocyte adhesion. In general, leukocyte/endothelial cell interactions such as capture, rolling, and firm adhesion can no longer be viewed as occurring in discrete steps mediated by individual families of adhesion molecules but rather as a series of overlapping synergistic interactions among adhesion molecules resulting in an adhesion cascade. These cascades thereby direct leukocyte migration, which is essential for the generation of effective inflammatory responses and the development of rapid immune responses.     

NADPH oxidase and lipid raft-associated redox signaling are required for PCB153-induced upregulation of cell adhesion molecules in human brain endothelial cells

Exposure to persistent organic pollutants, such as polychlorinated biphenyls (PCBs), can lead to chronic inflammation and the development of vascular diseases. Because cell adhesion molecules (CAMs) of the cerebrovascular endothelium regulate infiltration of inflammatory cells into the brain, we have explored the molecular mechanisms by which ortho-substituted polychlorinated biphenyls (PCBs), such as PCB153, can upregulate CAMs in brain endothelial cells. Exposure to PCB153 increased expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), as well as elevated adhesion of leukocytes to brain endothelial cells. These effects were impeded by inhibitors of EGFR, JAKs, or Src activity. In addition, pharmacological inhibition of NADPH oxidase or disruption of lipid rafts by cholesterol depleting agents blocked PCB153-induced phosphorylation of JAK and Src kinases and upregulation of CAMs. In contrast, silencing of caveolin-1 by siRNA interference did not affect upregulation of ICAM-1 and VCAM-1 in brain endothelial cells stimulated by PCB153. Results of the present study indicate that lipid raft-dependent NADPH oxidase/JAK/EGFR signaling mechanisms regulate the expression of CAMs in brain endothelial cells and adhesion of leukocytes to endothelial monolayers. Due to its role in leukocyte infiltration, induction of CAMs may contribute to PCB-induced cerebrovascular disorders and neurotoxic effects in the CNS.     

ANTI-ADHESION evolves to a promising therapeutic concept in oncology

Adhesion is a hallmark of haematological and solid cancer cells. All five classes of cell adhesion molecules (CAM) - integrins, cadherins, immunoglobulin-like CAMs, selectins and CD44s - are characteristically dysregulated in human cancer. Adhesion enables and promotes cancer-defining biological processes like growth, survival, migration, extravasation, homing, and metastasis. Furthermore, cell adhesion mediates drug resistance (CAM-DR) in multiple myeloma, malignant lymphoma, acute and chronic leukaemias, as well as in pancreatic cancer, neuroblastoma, small cell and non-small cell lung cancer, mesothelioma, colorectal carcinoma, and breast cancer. Cell adhesion protects from death by radiation, genotoxic chemotherapy, or targeted pathway inhibitors. Adhesion molecules are overexpressed on drug resistant cells (e.g. multiple myeloma or prostate cancer). Very recently, several cell adhesion mediated survival pathways have been elucidated, with key mediators being LFA-1, VLA-4, FAK, ILK, Src, PI3K, Akt, Ras, MEK, Erk, HMG-CoA reductase, Rho, Rho kinase, PKC, and NFkB. Because the surface and the intracellular targets are now known and because specific compounds are becoming increasingly available, first clinical trials regarding ANTI-ADHESION therapies are ongoing. However, in comparison to the comprehensive preclinical and clinical knowledge about CAMs, the number of drugs developed thusfar is quite low. ANTI-ADHESION strategies include targeting of surface antigens, inhibition of cell adhesion associated pathways, inhibition of CAM-DR, and targeted drug delivery. As ANTI-ADHESION is based on general characteristics of cancer cells independent of specific disease entities or treatment modalities, it may become a successful, low-toxic and broadly applicable concept in cancer treatment.     

Integrin alpha v beta 3 antagonists for anti-angiogenic cancer treatment

Direct contact between cellular and extracellular matrix (ECM) proteins is necessary for a diverse array of physiologic processes including cellular activation, migration, proliferation, and differentiation. These direct interactions are modulated by cell adhesion molecules (CAMs) such as integrins, selectins, cadherins, and immunoglobulins. Integrin signaling also plays a key role in tumor growth, angiogenesis, and metastasis. Recent advances in the discovery and characterization of CAMs and their receptors, most notably integrin alpha(v)beta(3), and the clarification of their roles in disease states have laid the groundwork for the development and clinical implementation of novel anti-cancer treatments. Integrin alpha (v)beta(3) is a glycoprotein membrane receptor which recognizes ECM proteins expressing an arginine-glycine-aspartic acid (RGD) peptide sequence. The receptor is highly expressed on activated tumor endothelial cells, but not resting endothelial cells and normal organ systems, thus making alpha(v)beta(3) an appropriate target for anti-angiogenic therapeutics. In addition, alpha(v)beta(3) is also expressed on tumor cells, allowing for both tumor cell and tumor vasculature targeting of anti-integrin therapy. Throughout the past decade, numerous patents have been published and issued using alpha(v)beta(3) antagonists for the prevention and/or treatment of cancer, with many antagonists demonstrating positive pre-clinical anti-angiogenic and anti-tumor results. This review will focus on the key points and distinguishing factors for patents which use antibodies, RGD peptides, non-RGD peptides, peptidomimetics, and amine salts as alpha(v)beta(3) antagonists.     

Biomechanics of cell interactions in shear fields

Cellular interactions play a key role in diverse biological processes within the cardiovascular system. Targeting of leukocytes to sites of inflammation is viewed as a multistage process of sequential involvement of distinct adhesion molecules on the leukocyte and endothelial cell (EC) surface that is dictated by the local fluid dynamic environment. For neutrophils, the initial contact and rolling along the vessel wall are mediated primarily by selecting. Subsequent firm adhesion requires activation of neutrophil P, integrins and binding to their ligand ICAM-1 on the EC surface. The final step of this cascade of events includes neutrophil transmigration to extravascular tissue space. The neutrophil model of emigration in inflammation has been extended and refined to account for monocyte and T cell interactions with ECs. Platelet adhesion to thrombogenic surfaces (i.e. immobilized von Willebrand factor) under flow follows the general principles of leukocyte extravasation. More specifically, platelet glycoprotein (GP) Ib alpha appears to mediate an initial selectin-like tethering platelet-vWf interaction, followed by alpha II beta beta 3 integrin activation and firm adhesion. Some of the signaling mechanisms associated with cellular interactions in inflammatory and thrombotic processes are discussed. These basic principles are also discussed in the context of tissue engineering research.     

植物多糖干预细胞黏附研究进展

黏附分子介导的细胞黏附是最基本的生命现象,也是炎症、免疫、感染、血栓形成、肿瘤转移、伤口愈合等生理病理过程的细胞学基础,干预黏附已成为疾病防治的重要策略。植物多糖特别是中草药中的多糖具有抗炎、抗肿瘤、抗感染、调节免疫、保护心血管等多样的药理作用,本文综述了植物多糖对疾病过程中细胞黏附的干预作用。     

Therapeutic strategies in autoimmune diseases by interfering with leukocyte endothelium interaction

The interaction of leukocytes with the vessel endothelium to facilitate the extravasation into the tissue represents a key process of the body's defense mechanisms. Excessive recruitment of leukocytes into the inflamed tissue in chronic diseases like autoimmune disorders could be prevented by interfering with the mechanisms of leukocyte extravasation. Significant progress in elucidating the molecular basis of the trafficking of leukocytes from the blood stream to the extravascular tissue has been achieved that enables new strategies for therapeutic approaches. The multistep process of leukocyte rolling, firm adhesion and transmigration through the endothelial wall is facilitated by a dynamic interplay of adhesion receptors on both leukocytes and endothelial cells as well as chemokines. In preclinical studies using various animal models, promising results have been received demonstrating that blocking of adhesion receptors of the selectin and integrin families improved the inflammation process in models of ulcerative colitis, autoimmune encephalomyelitis or contact hypersensitivity. In addition to the targeting of adhesion receptors by antibodies, small molecules that mimic epitopes of adhesion receptor ligands have been developed and successfully applied in animal models. Clinical studies revealed a limited response using antibodies to selectins or LFA-1 integrins compared with animal models. However, using humanized antibodies to the alpha4- integrin subunit significant efficacy has been demonstrated in autoimmune diseases like psoriasis, multiple sclerosis and inflammatory bowel disease.     

Cell adhesion molecules as pharmaceutical target in atherosclerosis

Cell adhesion molecules (CAMs) are transmembrane proteins that mediate adhesion and interactions between cells or cell and extra-cellular matrix. Increased expression and activation of CAMs in vascular endothelial cells and circulating leukocytes, as occurring in the settings of inflammation, hypercholesterolemia, hypertension and diabetes, stimulates leukocyte recruitment into the vascular endothelium, an important step in the pathogenesis of atherosclerosis. CAMs are a potential therapeutic target in clinical practice and in recent years pharmaceutical agents with specific effects on the production and function of these molecules have been studied and developed. This article reviews recent progress regarding pathophysiology of CAMs in atherogenesis and pharmaceutical products or chemicals that are active against CAMs, and assesses the possibilities for clinical developments in this area that might enhance the prevention, monitoring and treatment of atherosclerotic cardiovascular diseases.