Elastin peptides induced oxidation of LDL by phagocytic cells

The degradation products of one of the major component of vascular wall, elastin, have several important biological activities. Elastin peptides (KE) are mostly generated during vascular aging and the atherosclerotic process. They induce free radical and proteases production from cells, which are the major components of the atherosclerotic process. In the present study, we investigated whether the interaction between elastin peptides and neutrophils as well as monocytes contributes to low density lipoproteins (LDL) oxidation, being one of the most important initiator of the chronic inflammatory process contributing to the development of atherosclerosis. Here, we present data on the link between the elastin degradation products and LDL oxidation by the chemotactically attracted neutrophils and monocytes. The KE as well as the active epitope, the hexapeptide VGVAPG is able, in a differential concentration and time dependence, to induce the oxidation of LDL. KE is able to induce via the production of free radicals by neutrophils the oxidation of LDL very rapidly and in higher concentration compared to monocytes. These effects of KE are occurring through the stimulation of the 67 kDa elastin-laminin receptor (ELR), as demonstrated by the uncoupling effect of lactose. In our present study, the HDL was able to decrease the LDL oxidation by KE. This is a new mechanism by which elastin peptides might participate in the initiation and progression of the atherosclerotic process.     

Morphine attenuates endothelial cell adhesion molecules induced by the supernatant of LPS-stimulated colon cancer cells

A large reservoir of bacterial lipopolysaccharide (LPS) is available in the colon and this could promote colon cancer metastasis by enhancing tumor cell adhesion, intravasation, and extravasation. Furthermore, adhesion molecules like ICAM-1, VCAM-1, and E-selectin play important roles in the adhesion of tumor cells to endothelium. This study was designed to determine whether morphine can attenuate the expressions of adhesion molecules up-regulated by the supernatant of LPS-stimulated HCT 116 colon cancer cells (LPS-Sup). In this study, we divided to three groups by cell-growth medium of human umbilical vascular endothelial cells (HUVECs): the control group was incubated in growth factor-free endothelial medium, the Sup group was incubated in the supernatant of HCT 116 cells (Sup), and the LPS-Sup group was incubated in LPS-Sup. To observe effect of morphine to the adhesion molecules expressions in the LPS-Sup group, we co-treated morphine with LPS or added it to LPS-Sup. Adhesion molecule expressions on HUVECs in all three groups were measured during incubation period. Consquentially, ICAM-1, VCAM-1, and E-selectin expressions on HUVECs were significantly lower when morphine was co-treated with LPS than not co-treated. Thus, we suggest that morphine affects the expressions of adhesion molecules primarily by attenuating LPS stimuli on tumor cells.     

Mycobacterium tuberculosis alters expression of adhesion molecules on monocytic cells.

The host response to Mycobacterium tuberculosis is characterized by interactions between mononuclear cells, with recruitment and fusion of these cells culminating in granuloma formation. In addition, the host response to M. tuberculosis requires CD4+ T-cell reactivity, mediated by antigen-independent as well as antigen-dependent mechanisms. Thus, we hypothesized that cell adhesion molecules such as intercellular adhesion molecule 1 (ICAM-1; CD54) would participate in the response to infection with M. tuberculosis. Exposure of THP-1 cells derived from a monocyte/macrophage cell line to M. tuberculosis (1:1 bacterium/cell ratio) elicited a sustained increase (660% +/- 49% above resting level) in the expression of ICAM-1 that continued for at least 72 h. Neither the expression of vascular cell adhesion molecule 1 (VCAM-1; CD106) nor that of the integrins lymphocyte function-associated antigen 1 (LFA-1; CD11a/CD18) or CR3 (CD11b/CD18) was increased to a similar extent at corresponding time points. The increase in ICAM-1 protein expression was accompanied by an increase in steady-state mRNA (Northern [RNA] analysis). Neutralizing monoclonal antibodies directed against tumor necrosis factor alpha but not interleukin 1 alpha or interleukin 1 beta substantially abrogated the response to M. tuberculosis consistent with a paracrine or autocrine response. Continuous upregulation of the expression of ICAM-1 on mononuclear phagocytes induced by M. tuberculosis may mediate the recruitment of monocytes and enhance the antigen presentation of M. tuberculosis, thus permitting the generation and maintenance of the host response.     

Upregulation of costimulatory molecules induced by lipopolysaccharide and double-stranded RNA occurs by Trif-dependent and Trif-independent pathways

Both lipopolysaccharide (LPS) and double-stranded RNA (dsRNA) are adjuvants for the adaptive immune response, inducing upregulation of costimulatory molecules (UCM) on antigen-presenting cells. Trif, an adapter protein that transduces signals from Toll-like receptor 4 (TLR4) and TLR3, permits the induction of many cytokines, including interferon-beta, which signals through the type I interferon receptor. We show here that LPS-induced UCM was strictly dependent on the TLR4-->Trif axis, whereas dsRNA-induced UCM was only partly dependent on the TLR3-->Trif axis. But both LPS- and dsRNA-induced UCM were entirely dependent on type I interferon receptor signaling. These findings show that UCM involves an autocrine or paracrine loop, and indicate that an alternative TLR3-independent, Trif-independent pathway contributes to dsRNA-induced UCM.     

Hodgkin''s cells express a novel pattern of adhesion molecules.

Adhesion molecules play an important role in the functioning of the immune system, particularly with regard to cell-cell interactions and antigen presentation. Several adhesion molecules are expressed on Hodgkin's disease-derived cell lines and these are important in their molecular interactions as antigen presenting cells (APC). There are no data regarding the expression of many of these adhesion molecules on Reed-Sternberg cells and its mononuclear variant (Hodgkin's cells (HC)) present in pathological material. To obtain this information we undertook an immunohistological study on material from 18 cases of Hodgkin's disease using a panel of MoAbs to examine the expression of adhesion molecules on HC. The HC were shown to express the integrin beta 1 subfamily molecules, LFA-1 (CD11a) and p150,95 (CD11c) in high density but lacked CR3 (CD11b). All of the immunoglobulin gene superfamily adhesion molecules studied were present to some degree on HC, with ICAM-2, in particular, showing moderate to strong expression in most cases. The Hermes antigen CD44 was present in high density but leukosialin (CD43), another molecule present on diverse leucocyte types, was, in general, not detected on HC. These new data showing that ICAM-1, ICAM-2 and LFA-3 are, like LFA-1, expressed on HC emphasize the ability of HC to act as APC. The known adhesion molecule phenotype of the recently defined haematopoietic lineage of human dendritic cells (DC) is broadly similar to that of HC, perhaps supporting the hypothesis that some HC represent a malignancy of an APC (DC) lineage.     

Upregulation and co-localization of connexin43 and cellular adhesion molecules in inflammatory renal disease

Connexin43 (Cx43) is a major component of gap junctions. These are widely distributed in the human kidney and are thought to be involved in the inflammatory response and in the regulation of cell growth. Cellular adhesion molecules (CAMs) are also thought to be important in these processes, where they possibly facilitate gap junction formation. The aims of the current study were to define for the first time the expression of Cx43 in inflammatory glomerulonephritis and to compare the localization of this connexin with that of the intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Human renal biopsies and control sections of normal human kidney were stained using the alkaline phosphatase/anti-alkaline phosphatase immunohistochemical technique, demonstrating that Cx43 was strongly expressed on inflammatory cells, on damaged tubular cells, and on interstitial cells. This pattern of expression was paralleled closely by that of ICAM-1 and, to a lesser extent, by that of VCAM-1. Cx43 is therefore primarily implicated in tubulointerstitial inflammation.© 1997 John Wiley & Sons, Ltd.     

Expression of adhesion molecules by endothelial cells of early human decidua

The expression of adhesion molecules by endothelial cells (EC) of early human decidua was studied with monoclonal antibodies and the immunoperoxidase technique. Although E-selectin, INCAM-110 and VCAM-1 were poorly detected on decidual EC, ICAM-1, P-selectin and DR antigens were highly expressed by these cells, some of which showed high endothelial venule-like morphology. Our results suggest that decidual EC are activated, and are probably involved in the active recruitment of leucocytes.     

Expression of leukocyte adhesion molecules by endothelial cells seeded on various polymer surfaces

Although endothelial cell seeding in small-diameter vascular prostheses significantly improves graft survival, the detachment of adherent endothelial cells after the restoration of circulation remains one of the major obstacles. Because in vivo experiments indicate that leukocyte infiltration is involved in endothelial cell loss, we hypothesize that seeded endothelial cells become activated and express leukocyte adhesion molecules and cytokines because of an interaction with the underlying polymer surface. The aim of this study was to investigate the expression of the leukocyte adhesion molecules ICAM-1, VCAM-1, PECAM-1, and E-selectin by cultured human umbilical vein endothelial cells (HUVECs) and human adipose microvascular endothelial cells (HAMVECs). The cells were seeded on tissue culture poly(styrene) and the vascular graft materials Dacron and Teflon. The results of this study indicate that the expression of leukocyte adhesion molecules by cultured endothelial cells is mainly affected by the endothelial cell origin, that is, umbilical vein or adipose tissue. Expressions of both ICAM-1 and E-selectin by HUVECs and HAMVECs are characterized by the presence of two cell populations with distinct levels of expression. With respect to endothelial cell seeding in vascular prostheses, the increased expression of E-selectin by microvascular endothelial cells deserves further attention.     

Pokeweed-mitogen induced lymphocyte proliferation: the effect of stimulation on mononuclear phagocytic cells.

Human peripheral blood mononuclear cells were stimulated with pokeweed mitogen (PWM) to study the role of mononuclear phagocytic cells (MNP) in lymphocyte proliferation. MNP were identified by cytoplasmic alpha-naphthyl acetate esterase, by the capacity of phagocytosis and by lysozyme synthesis. It appeared that after 3 days of stimulation with PWM all MNP disappeared from the cultures and remained absent during prolonged culture in mitogen-free medium. In non-stimulated cultures MNP remained. The disappearance of MNP from cell cultures was caused by a lymphocyte-derived factor, which was transferable by cell-free supernatants of stimulated mononuclear cells. From experiments in which cultures were treated with different concentations of PWM and from pre-culture experiments, it could be shown that in vitro lymphocyte proliferation required both non-stimulated lymphocytes and freshly prepared MNP. In addition, the decreasing concentration of PWM as stimulating agent, resulted in a decreasing proliferation of lymphocytes, which was inversely proportional to the presence of MNP.     

Heterogeneous expression of cell adhesion molecules by endothelial cells in ARDS

ARDS (acute respiratory distress syndrome) can be associated with septic shock and multiple organ failure caused by an uncontrolled systemic inflammatory response to Gram-negative bacterial infection. While in animal models the key role of the endothelial adhesion molecules ICAM-1, E-selectin, and VCAM in ARDS has been extensively studied, there are scarcely any corresponding pathomorphological studies of human lung tissue. Hence, little is known about whether there is a comparable, or even heterogeneous, expression pattern of these molecules in the human pulmonary vasculature. This study was therefore undertaken to investigate the immunohistochemical expression of the constitutively expressed PECAM (CD31) and the inducible molecules ICAM-1, E-selectin, and VCAM in ARDS lungs from patients who had died in septic shock induced by Gram-negative bacteria. While in all specimens (ARDS and normal lungs) there was homogeneous strong expression of PECAM in all vessels, ICAM-1 was clearly up-regulated in ARDS lungs. E-selectin and VCAM were not expressed by endothelial cells (ECs) in normal lungs, but in ARDS lungs there was strong expression of both molecules in larger vessels, while in the capillaries there was only mosaic-like weak expression of a few ECs. This immunohistochemical investigation demonstrates the induction and up-regulation of adhesion molecules in human ARDS lungs, comparable to that described in animal models. There is also markedly heterogeneous expression of E-selectin and VCAM, indicating toporegional differences in the function of pulmonary ECs.     

Adhesion molecules on intermediate TCR cells. I. Unique expression of adhesion molecules, CD44+ L-selectin-, on intermediate TCR cells in the liver and the modulation of their adhesion by hyaluronic acid.

In addition to thymus-derived T cells, it was demonstrated recently that extrathymically differentiated T cells exist in the liver and other immune organs of mice. Since such extrathymic T cells have T-cell receptors (TCR) of intermediate intensity (i.e. intermediate TCR cells) and constitutively express IL-2 receptor beta-chain (IL-2R beta) similar to natural killer (NK) cells, they are easily distinguished from thymus-derived T cells with a TCR-bright+ IL-2R beta- phenotype (i.e. bright TCR cells). In the present study, the expression of adhesion molecules CD44 and L-selectin was compared between these T-cell subsets. Intermediate TCR cells in the liver and other organs were found to be CD44+ L-selectin- and, inversely, bright TCR cells were CD44- L-selectin+. CD3- IL-2R beta+ NK cells were also estimated to be CD44+ L-selectin-. Hyaluronic acid, which is known to adhere to a CD44 ligand, bound to intermediate TCR cells, but not to bright TCR cells. Among many extracellular matrices, hyaluronic acid induced a prominent decrease in the numbers and proportions of intermediate TCR cells and NK cells in the liver from 6 to 24 hr after in vivo administration. The half-life span of injected hyaluronic acid was approximately 7 hr in the plasma. These results suggest that the CD44 molecule, which is uniquely expressed on intermediate TCR cells and NK cells, is eventually associated with their adhesion to the sinusoidal walls in the liver.     

黏附分子整合素CD11c对细胞因子诱导的杀伤细胞治疗胃癌疗效的影响

探讨胃癌组织中黏附分子CD11c的表达与患者预后的关系,并分析CD11c的表达对细胞因子诱导的杀伤细胞(CIK)治疗胃癌患者复发和死亡风险的影响。采用免疫组织化学染色法确定CD11c表达;应用COX多因素模型分析化疗联合CIK治疗组(下称联合组)与CD11c表达状态联合影响胃癌复发和死亡的风险。单因素统计学分析显示:联合组+CD11c高表达、联合组+CD11c低表达、化疗组+CD11c高表达和化疗组+CD11c低表达患者的中位无瘤生存时间及中位生存时间差异有统计学意义(均P<0.01)。在调整了性别、年龄、胃癌部位、肿瘤大小、分期、转移和治疗方式等混杂因素后,与联合组+CD11c高表达组相比,化疗组+CD11c低表达组复发和死亡风险显著增加(HR=5.76,95%CI=2.42~13.70;HR=5.00,95%CI=2.22~11.12),且联合组+CD11c高表达、联合组+CD11c低表达、化疗组+CD11c高表达和化疗组+CD11c低表达患者复发和死亡的HR呈上升趋势(趋势检验,均P<0.01)。肿瘤组织中CD11c高表达的胃癌患者采用化疗联合CIK细胞治疗可显著延长患者的生存时间,CD11c高表达可作为CIK细胞治疗的纳入标准。     

钙离子载体上调K562细胞B7分子表达

目的：探讨钙离子载体（Calcium ionorphore,CI）对慢性髓系白血病细胞株K562细胞表面B7分子表达的上调作用.方法：将生长状态良好的K562细胞在含CI（375 ng/ml）的培养基中培养,以不含CI培养的K562细胞作对照组.培养0、48和96小时后台盼蓝拒染法检测细胞数和细胞存活率,流式细胞仪检测培养前及培养96小时后细胞表面B7分子的表达情况,MTT比色法检测其刺激同种异体T细胞增殖的作用.结果：K562细胞表面B7分子缺如或低表达;用含CI的培养基培养96小时后,可显著上调B7分子的表达,且能明显激活同种异体T细胞.培养前后细胞形态无明显变化,加CI培养的K562细胞较不加CI培养的细胞生长缓慢.结论：慢性髓系白血病细胞株K562细胞表面存在B7分子表达缺陷,CI可上调其B7分子.CI可能有抑制K562细胞生长的作用.     

T-T cell interactions are mediated by adhesion molecules.

The mechanism by which T cells signal other T cells is not well defined. This was investigated by studying the ability of circulating T cells to induce the proliferation of autologous T cell clones. Peripheral blood T cells activated by cross-linking of the CD3/T cell receptor complex, which increased the expression of cell adhesion molecules LFA-1, LFA-3 and ICAM-1, induced the proliferation of autologous T cell clones. Irradiated antigen-activated peripheral blood T cells could also induce the proliferation of T cell clones which could not recognize that antigen. T-T cell activation required cell contact, was not major histocompatibility complex (MHC) restricted and was blocked by monoclonal antibodies directed against adhesion molecules CD2 and LFA-3 but was not blocked by antibody to class II MHC determinants. As CD2 is the natural ligand for LFA-3, increased expression of T cell surface adhesion molecules LFA-1, ICAM-1 and particularly LFA-3 during an inflammatory response may rapidly recruit T cells that are activated through the CD2 pathway. These results allow a simplified model to explain how relatively few antigen/MHC-specific T cells can recruit large numbers of non-antigen-specific T cells in the generation of an inflammatory response and postulates a novel role of the CD2 molecule in T cell immune function.     

Demystified ... adhesion molecules.

The cell adhesion molecules are ubiquitous recognition molecules that allow cells to communicate with one another and their environment. Through these molecules, complex alterations in the cytoplasmic messenger pathways and the microfilamentous cytoskeleton can lead to profound alterations in cell division, differentiation, behaviour, and function (fig 9). It is difficult to conceive of a group of molecules that could be more important to pathologists and to their understanding of disease processes.     

Embryonic neural cell adhesion molecules on human natural killer cells

The neural cell adhesion molecules (NCAM) are surface glycoproteins that were first described in brain tissue. NCAM mediate adhesion in a variety of cell-cell interactions. In the present study we show that the so-called "embryonic" NCAM, i.e., the highly polysialylated forms of these proteins, are expressed on natural killer cells and some CD3+ cells in man. Homotypic binding of NCAM, believed to be of importance for cell-cell adhesion in neural tissues, appears not to be essential for NK cell-mediated killing. Yet, NCAM might be involved in NK cell migration, homing or related functions.     

Circulating adhesion molecules in sarcoidosis.

Sarcoidosis is a disease of unknown etiology characterized by non-caseating granulomata together with a number of systemic abnormalities. We have recently shown these include increased expression of the integrins CD11/CD18 on peripheral blood leucocytes. Here we have measured serum levels of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) in 23 patients and 14 normal controls using antigen capture sandwich ELISAs. Median circulating E-selectin levels in the patients were nearly three times those of the controls (P < 0.0001, Mann-Whitney U-test), whilst ICAM-1 but not VCAM-1 levels were only slightly elevated. These results show that endothelial cell activation and shedding of E-selectin into the circulation are additional features of the pathology of sarcoidosis.