可溶性血管细胞黏附分子-1对过敏性紫癜早期病情判断的观察

血管细胞黏附分子-1(vascular cell adhesion molecule,VCAM-1)是一种重要的细胞黏附分子,主要表达于血管内皮细胞上,与淋巴细胞、单核细胞、嗜酸性粒细胞等上迟现抗原-4(VLA-4)结合,参与了过敏性疾病、全身性小血管炎的发病过程。本研究旨在通过血清中SVCAM-1的检测,以探讨其在过敏性紫癜(HSP)早期诊断中的价值。     

血管内皮祖细胞的研究进展

骨髓含有一群能够迁移到外周血并分化为成熟内皮细胞的祖细胞，这些细胞被称为血管内皮祖细胞（Endothelial progenitor cell，EPC）。越来越多的证据显示，EPC参与生理性及病理性血管形成。临床前研究也证明EPC在缺血肢体或心肌中向血管新生部位迁移，并参与肿瘤血管发生。因此，EPC可能是一种很有前景的血管性及肿瘤性疾病的治疗靶点。     

人脂联素基因重组腺病毒对内皮细胞MCP-1和ICAM-1表达的影响

脂联素（adiponectin,ADPN）是脂肪细胞分泌的一种特异性蛋白质,具有改善胰岛素抵抗、抗炎、抗动脉粥样硬化、降血糖、保护血管内皮等作用[1],生理浓度范围内的脂联素通过抑制NF-κB信号传导通路能够剂量依赖性地抑制肿瘤坏死因子（TNF-α）诱导的血管内皮细胞黏附分子的表达。本研究通过将人脂联素基因重组腺病毒感染人脐静脉内皮细胞（human umbilical veins endothelial cells,HUVECs）,研究其对人脐静脉内皮细胞分泌单核细胞超化因子1（MCP-1）和细胞间粘附分子（intercellular adhesion molecule,ICAM-1）和mRNA表达的影响。     

血管细胞粘附分子-1与骨髓基质细胞

血管细胞粘附分子-1(vascular cell adhesion molecule 1,VCAM-1)是一种重要的细胞粘附分子,VCAM-1与VLA-4结合后导致构型改变,都成为高亲和力的粘附分子,处于活化状态,能使造血干细胞在骨髓基质细胞上形成聚集体,并参与造血干细胞的迁移、归巢、定居和分化等功能。在病理条件或受辐射时的VCAM-1无论是表达还是功能都有很大的变化。     

内皮祖细胞移植研究进展

内皮祖细胞（endothelial progenitor cell，EPC）是一类能增殖并分化为血管内皮细胞，但尚未表达成熟血管内皮细胞表型，也未形成血管的前体细胞。研究发现，EPC不仅参与人胚胎血管生成，同时也参与出生后血管新生和内皮损伤后的修复过程。因而，近年来一些国内外学者在探索通过EPC移植来促进血管新生和维持内皮功能完整，希望为一些临床疾病的治疗提供新的策略。作者就这方面的研究进展作一综述。     

全反式维甲酸对外周血干细胞移植患者骨髓基质细胞黏附分子表达及黏附力的影响

本研究探讨全反式维甲酸（all—transretinoic acid，ATRA）能否促进外周血造血干细胞移植（peripheral blood stem cell transplantation，PBSCT）预处理致伤的骨髓基质细胞（bonemarrow stromal cells，BMSC）功能的恢复。用流式细胞术检测27例造血干细胞移植患者预处理前后BMSC表面细胞间黏附分子-1（intercellular adhesion molecule—1，ICAM-1）和血管黏附分子-1（vascular adhesion molecule-1，VCAM-1）表达，用放射免疫法测定BMSC培养上清液中可溶性ICAM—1（sICAM-1）水平以及BMSC对CD34^＋细胞的黏附率，并检测浓度分别为0、01、0．1、1μmol/L的ATRA作用后上述指标的动态变化。结果显示：PBSCT预处理后，BMSC表面ICAM-1和VCAM-1的表达以及BMSC培养上清液中sICAM-1的表达水平降低，BMSC对CD34^＋细胞黏附率降低，而在ATRA作用后，BMSC表面ICAM—1表达增加，培养上清液中sICAM-1水平升高，BMSC对CD34^＋细胞的黏附率增加．但VCAM-1表达变化不明显。结论：全反式维甲酸可部分修复受损的BMSC的黏附功能，有助于促进骨髓造血重建。     

骨髓基质细胞迁移机制研究进展

骨髓基质细胞（BMSC）是骨髓细胞中除去造血干细胞（非黏附细胞）之外的黏附细胞部分，也称为塑料黏附细胞、克隆形成单位成纤维细胞或骨髓间充质干细胞（MSC）。BMSC向组织迁移及穿过内皮的机制还不清楚，很可能通过损伤组织表达特殊的受体或配体促进BMSC向其迁移。趋化因子受体及其配体是影响白细胞向炎症区迁移过程中的重要成分。最近的研究表明，BMSC也表达趋化因子受体及配体。另外，一些在白细胞迁移、穿过内皮细胞过程起重要作用的黏附分子在BMSC中也有表达。     

脑梗死患者血清可溶性细胞间黏附分子-1和P-选择素水平变化的临床意义

黏附分子在脑梗死后再灌注损伤的炎症反应中起重要作用。可溶性细胞间黏附分子-1（sICAM-1）主要由活化的血管内皮细胞表达,P-选择素在血小板和血管内皮细胞均有显著表达,他们介导了白细胞紧密黏附至血管内皮,进而迁移至内皮下空隙,加重了内皮损伤,参与缺血脑组织的炎性反应,加重脑组织损伤。我们检测了急性脑梗死患者sICAM-1和P-选择素水平变化,探讨其在脑梗死中的意义。     

内皮微粒在肾移植急性排斥反应中的诊断作用

背景：血管内皮细胞的变化与移植排斥反应的关系极为密切,内皮微粒脱落于激活或凋亡的内皮细胞,能直接而特异地反映血管内皮细胞的变化,检测血浆中内皮微粒对肾移植排斥反应的诊断监测具有一定的理论和实际意义。目的：探讨肾移植急性排斥反应时循环内皮微粒的数量和表型的变化及与急性排斥反应之间的关系。方法：建立同基因和同种异基因大鼠腹腔原位肾移植模型;移植后5d苏木精-伊红染色观察肾组织的病理学改变,并进行Banff评分;采用免疫组化法检测肾组织中细胞间黏附分子1表达;采用流式细胞术检测血浆中CD144＋内皮微粒数量及细胞间黏附分子1＋/CD144＋内皮微粒的数量;分析内皮微粒的数量和表型与肾组织病理变化的关系。结果与结论：与同基因移植组比较,异基因移植组Bnaff评分明显增加（P〈0.01）,肾组织中细胞间黏附分子1表达明显增强（P〈0.01）;与同基因移植组比较,异基因移植组CD144＋内皮微粒的数量和携带细胞间黏附分子1的内皮微粒的水平明显增加（P〈0.01）。内皮微粒的数量与移植肾急性排斥反应的程度呈正相关（P〈0.01）,携带细胞间黏附分子1内皮微粒的水平与移植肾脏中细胞间黏附分子1的表达呈正相关（P〈0.01）。提示肾移植后对内皮微粒数量和表型进行检测对诊断急性排斥反应的发生有一定意义。     

心血管支架置入后血管内皮损伤的修复与再内皮化

心血管支架置入后常发生冠状动脉无再流、急性和亚急性血栓形成、栓塞等心血管事件.在血管内皮损伤后,内皮祖细胞能归巢至损伤血管内皮局部,加快损伤血管再内皮化,抑制病理性新生内膜形成,在血管内皮损伤修复中起着重要作用.通过内皮细胞种植、内皮祖细胞动员分化、加速宿主内皮细胞的增殖迁移等途径可实现血管支架再内皮化.血管内皮生长因子、成纤维细胞生长因子、粒细胞集落刺激因子以及相关化学药物、抗体等均可加速血管支架再内皮化.同时,黏附蛋白、黏附多肽等能够促进内皮的黏附.支架内皮化的效果,取决于种植的内皮细胞数、细胞黏附率,贴壁细胞暴露于血流后的保留率,其中如何提高内皮细胞的黏附率,是目前最需要解决的问题.     

Adhesion of human B cells to follicular dendritic cells involves both the lymphocyte function-associated antigen 1/intercellular adhesion molecule 1 and very late antigen 4/vascular cell adhesion molecule 1 pathways

Presentation of antigen in the form of immune complexes to B lymphocytes by follicular dendritic cells (FDC) is considered to be a central step in the generation of memory B cells. During this process, which takes place in the microenvironment of the germinal center, B cells and FDC are in close physical contact. In the present study, we have explored the molecular basis of FDC-B cell interaction by using FDC and B cells derived from human tonsils. We found that FDC express high levels of the adhesion receptors intercellular adhesion molecule 1 (ICAM-1 [CD54]) and vascular cell adhesion molecule 1 (VCAM-1), while the B lymphocytes express lymphocyte function-associated antigen 1 (LFA-1 [CD11a/18]), very late antigen 4 (VLA-4 [CD49d], and CD44. Furthermore, we established that both the LFA-1/ICAM-1 and VLA-4/VCAM-1 adhesion pathways are involved in FDC-B lymphocyte binding, and therefore, these pathways might be essential in affinity selection of B cells and in the formation of B memory cells.     

Analysis of T cell stimulation by superantigen plus major histocompatibility complex class II molecules or by CD3 monoclonal antibody: costimulation by purified adhesion ligands VCAM-1, ICAM-1, but not ELAM-1.

Many ligands of adhesion molecules mediate costimulation of T cell activation. The generality of this emerging concept is best determined by using model systems which exploit physiologically relevant ligands. We developed such an "antigen-specific" model system for stimulation of resting CD4+ human T cells using the following purified ligands: (a) major histocompatibility complex class II plus the superantigen Staphylococcus enterotoxin A, to engage the T cell receptor (TCR); (b) adhesion proteins vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and endothelial leukocyte adhesion molecule 1 (ELAM-1), to provide potential cell surface costimulatory signals; and (c) recombinant interleukin 1 beta (rIL-1 beta)/rIL-6 as costimulatory cytokines. In this biochemically defined system, we find that resting CD4+ T cells require costimulation in order to respond to TCR engagement. This costimulation can be provided by VCAM-1 or ICAM-1; however adhesion alone is not sufficient since ELAM-1 mediates adhesion but not costimulation. The cytokines IL-1 beta and IL-6 by themselves cannot mediate costimulation, but augment the adhesion ligand-mediated costimulation. Direct comparison with the model of TCR/CD3 engagement by CD3 monoclonal antibody demonstrated comparable costimulatory requirements in both systems, thereby authenticating the commonly used CD3 model. The costimulation mediated by the activation-dependent interaction of the VLA-4 and LFA-1 integrins with their respective ligands VCAM-1 and ICAM-1 leads to increased IL-2R alpha (CD25) expression and proliferation in both CD45RA+ CD4+ and CD45RO+ CD4+ T cells. The integrins also regulate the secretion of IL-2, IL-4, and granulocyte/macrophage colony-stimulating factor. In contrast the activation-independent adhesion of CD4+ T cell to ELAM-1 molecules does not lead to T cell stimulation as measured by proliferation, IL-2R alpha expression, or cytokine release. These findings imply that adhesion per se is not sufficient for costimulation, but rather that the costimulation conferred by the VLA-4/VCAM-1 and LFA-1/ICAM-1 interactions reflects specialized accessory functions of these integrin pathways. The new finding that VLA-4/VCAM-1 mediates costimulation adds significance to observations that VCAM-1 is expressed on a unique set of potential antigen-presenting cells in vivo.     

Role of beta 1 and beta 2 integrins in the adhesion of human CD34hi stem cells to bone marrow stroma.

Hematopoietic stem cell interaction with elements of the underlying stroma is essential for sustained normal hematopoiesis. Here we have determined that adhesion receptors in the integrin family play a role in promoting adhesion of human hematopoietic stem cells to cultured human marrow stromal cells. Enriched CD34hi progenitor cells expressed VLA-4, VLA-5, and at least one or more beta 2 integrins. Homogeneous marrow stromal cell monolayers capable of supporting proliferation of cocultivated CD34hi cells expressed VCAM-1 and fibronectin (ligands for VLA-4 and VLA-5) as well as ICAM-1 (ligand for LFA-1 and Mac-1). Adhesion-blocking experiments indicated that VLA-4/VCAM-1, VLA-5/fibronectin, and beta 2-integrin/ICAM-1 pathways all are important for CD34hi cell attachment to stromal cells. Consistent with this suggestion, IL-1 stimulation of stromal cells caused both increased VCAM-1 and ICAM-1 expression and increased attachment by CD34hi bone marrow cells. In addition, CD34hi cells utilized VLA-4 to adhere to purified VCAM-1 and employed VLA-5 (and to a lesser extent VLA-4) to adhere to purified fibronectin. Together these results suggest that CD34hi stem cells may utilize multiple integrin-mediated adhesion pathways to localize within specialized microenvironmental niches created by marrow stromal cells.     

Integrin mediated adhesion of mononuclear cells from patients with familial hypercholesterolemia

BACKGROUND: Low-density lipoproteins (LDL) can induce the adhesion of monocytes to endothelial cells. Monocytes of patients with familial hypercholesterolemia (FH) are exposed to high concentrations of LDL, and it has been reported that adhesiveness of these cells in hypercholesterolemic patients is enhanced. We investigated whether LFA-1 or VLA-4 mediated adhesion is altered in FH patients and whether HMG-CoA reductase inhibitors influence this adhesion. PATIENTS AND METHODS: LFA-1 and VLA-4 mediated adhesion to ICAM-1 and VCAM-1 coated beads was investigated using freshly isolated monocytes and T-lymphocytes from patients with homozygous FH, heterozygous FH (before and after cholesterol lowering treatment), and from controls. In addition, the expression of beta1- and beta2-integrins on these cells was determined. RESULTS: Both LFA-1 and VLA-4 mediated adhesion and integrin expression of monocytes and CD3+ cells from patients with homozygous FH and heterozygous FH was similar to that of monocytes from a control population. Treatment with HMG-CoA reductase inhibitors did not affect the adherence to ICAM-1 or VCAM-1, and did not influence the expression of integrins. CONCLUSIONS: In contrast to studies by others, we demonstrated in the present study that the actual LFA-1 and VLA-4 mediated adhesion of T-lymphocytes and monocytes is not altered in patients with FH.     

Role of vascular cell adhesion molecule 1/very late activation antigen 4 and intercellular adhesion molecule 1/lymphocyte function-associated antigen 1 interactions in antigen-induced eosinophil and T cell recruitment into the tissue

To determine the role of vascular cell adhesion molecule 1 (VCAM- 1)/very late activation antigen 4 (VLA-4) and intercellular adhesion molecule 1 (ICAM-1)/lymphocyte function-associated antigen 1 (LFA-1) interactions in causing antigen-induced eosinophil and T cell recruitment into the tissue, we studied the effect of the in vivo blocking of VCAM-1, ICAM-1, VLA-4, and LFA-1 by pretreatment with monoclonal antibodies (mAb) to these four adhesion molecules on the eosinophil and T cell infiltration of the trachea induced by antigen inhalation in mice. The in vivo blocking of VCAM-1 and VLA-4, but not of ICAM-1 and LFA-1, prevented antigen-induced eosinophil infiltration into the mouse trachea. On the contrary, the in vivo blocking of VCAM-1 and VLA-4, but not of ICAM-1 and LFA-1, increased blood eosinophil counts after antigen challenge, but did not affect blood eosinophil counts without antigen challenge in sensitized mice. Furthermore, the expression of VCAM-1 but not ICAM-1 was strongly induced on the endothelium of the trachea after antigen challenge. In addition, pretreatment with anti-IL-4 mAb decreased the antigen-induced VCAM-1 expression only by 27% and had no significant effect on antigen-induced eosinophil infiltration into the trachea. The in vivo blocking of VCAM- 1 and VLA-4 inhibited antigen-induced CD4+ and CD8+ T cell infiltration into the trachea more potently than that of ICAM-1 and LFA-1. In contrast, regardless of antigen challenge, the in vivo blocking of LFA- 1, but not of ICAM-1, increased blood lymphocyte counts more than that of VCAM-1 and VLA-4. These results indicate that VCAM-1/VLA-4 interaction plays a predominant role in controlling antigen-induced eosinophil and T cell recruitment into the tissue and that the induction of VCAM-1 expression on the endothelium at the site of allergic inflammation regulates this eosinophil and T cell recruitment.     

Inhibition of LFA-1/ICAM-1 and VLA-4/VCAM-1 as a therapeutic approach to inflammation and autoimmune diseases

This review focuses on providing insights into the structural basis and clinical relevance of LFA-1 and VLA-4 inhibition by peptides and small molecules as adhesion-based therapeutic strategies for inflammation and autoimmune diseases. Interactions of cell adhesion molecules (CAM) play central roles in mediating immune and inflammatory responses. Leukocyte function-associated antigen (LFA-1, alpha(L)beta(2), and CD11a/CD18) and very late antigen (VLA-4, alpha(4)beta(1), and CD49d/CD29) are members of integrin-type CAM that are predominantly involved in leukocyte trafficking and extravasation. LFA-1 is exclusively expressed on leukocytes and interacts with its ligands ICAM-1, -2, and -3 to promote a variety of homotypic and heterotypic cell adhesion events required for normal and pathologic functions of the immune systems. VLA-4 is expressed mainly on lymphocyte, monocytes, and eosinophils, but is not found on neutrophils. VLA-4 interacts with its ligands VCAM-1 and fibronectin (FN) CS1 during chronic inflammatory diseases, such as rheumatoid arthritis, asthma, psoriasis, transplant-rejection, and allergy. Blockade of LFA-1 and VLA-4 interactions with their ligands is a potential target for immunosuppression. LFA-1 and VLA-4 antagonists (antibodies, peptides, and small molecules) are being developed for controlling inflammation and autoimmune diseases. The therapeutic intervention of mostly mAb-based has been extensively studied. However, due to the challenging relative efficacy/safety ratio of mAb-based therapy application, especially in terms of systemic administration and immunogenic potential, strategic alternatives in the forms of peptide, peptide mimetic inhibitors, and small molecule non-peptide antagonists are being sought. Linear and cyclic peptides derived from the sequences of LFA-1, ICAM-1, ICAM-2, VCAM-1, and FN C1 have been shown to have inhibitory effects in vitro and in vivo. Finally, understanding the mechanism of LFA-1 and VLA-4 binding to their ligands has become a fundamental basis in developing therapeutic agents for inflammation and autoimmune diseases.     

Lymphocyte function-associated antigen 1 dominates very late antigen 4 in binding of activated T cells to endothelium

Lymphocyte function-associated antigen 1/intercellular adhesion molecule 1 (LFA-1/ICAM-1)-and very late antigen 4/vascular cell adhesion molecule 1 (VLA-4/VCAM-1)-mediated adhesion of T lymphocytes to endothelial cells (EC) can be regulated by increased expression of ICAM-1 and VCAM-1 upon cytokine treatment of EC, or by activation of the integrin molecules LFA-1 and VLA-4 on T cells. Here, we provide evidence that preferential usage of LFA-1 over VLA-4 is yet another mechanism to control T cell adhesion. We observed that binding of activated T lymphocytes, as opposed to resting T cells, to EC is essentially mediated through LFA-1 and not through VLA-4. VLA-4- mediated adhesion of T cells to EC is only found when LFA-1 is not expressed or not functional, as observed for several T cell leukemia cell lines. These results suggest that LFA-1-mediated adhesion dominates and may downregulate VLA-4-mediated adhesion through an unidentified mechanism.     

The CD44-initiated pathway of T-cell extravasation uses VLA-4 but not LFA-1 for firm adhesion

Leukocytes extravasate from the blood in response to physiologic or pathologic demands by means of complementary ligand interactions between leukocytes and endothelial cells. The multistep model of leukocyte extravasation involves an initial transient interaction ("rolling" adhesion), followed by secondary (firm) adhesion. We recently showed that binding of CD44 on activated T lymphocytes to endothelial hyaluronan (HA) mediates a primary adhesive interaction under shear stress, permitting extravasation at sites of inflammation. The mechanism for subsequent firm adhesion has not been elucidated. Here we demonstrate that the integrin VLA-4 is used in secondary adhesion after CD44-mediated primary adhesion of human and mouse T cells in vitro, and by mouse T cells in an in vivo model. We show that clonal cell lines and polyclonally activated normal T cells roll under physiologic shear forces on hyaluronate and require VCAM-1, but not ICAM-1, as ligand for subsequent firm adhesion. This firm adhesion is also VLA-4 dependent, as shown by antibody inhibition. Moreover, in vivo short-term homing experiments in a model dependent on CD44 and HA demonstrate that superantigen-activated T cells require VLA-4, but not LFA-1, for entry into an inflamed peritoneal site. Thus, extravasation of activated T cells initiated by CD44 binding to HA depends upon VLA-4-mediated firm adhesion, which may explain the frequent association of these adhesion receptors with diverse chronic inflammatory processes.     

急性髓系白血病细胞侵袭能力与粘附分子表达产在系探讨

探讨白血病的细胞浸润及转移与粘附分子表达的关系。胜免疫组织化学ＡＰＡＡＰ、免疫印迹方法研究５０例急性髓系白血病骨髓和外周血白血病细胞粘附分子ＶＬＡ４（ＣＤ４９ｄ）、ＬＦＡ１（ＣＤＤ１１ａ）的表表达。结果发现ＡＭＬ浸润组ＣＤ４９ｄ、ＣＤ１１ａ表达较非浸润组显著增高。