PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Cell Adhesion Molecules”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed1998

Rat neutrophils express alpha4 and beta1 integrins and bind to vascular cell adhesion molecule-1 (VCAM-1) and mucosal addressin cell adhesion molecule-1 (MAdCAM-1).

The alpha4 integrins, which are constitutively expressed on all human leukocyte subtypes except neutrophils, interact with vascular cell adhesion molecule-1 (VCAM-1) and mucosal addressin cell adhesion molecule (MAdCAM-1) on endothelium to mediate selective recruitment of leukocyte subpopulations, other than neutrophils, to sites of inflammation. However, here we report that a different paradigm of leukocyte recruitment may exist in the rat. Flow cytometric analysis of rat neutrophils using a panel of monoclonal antibodies which recognize rat alpha4 and beta1 integrins showed consistent, low levels of expression. Although alpha4 was expressed at lower levels on neutrophils than all other rat leukocytes, this level of expression was sufficient to mediate significant levels of alpha4- and beta1-dependent neutrophil adhesion to rat and human VCAM-1, and alpha4-dependent, but beta1-independent, adhesion to human MAdCAM-1. These data suggest that rat neutrophils, unlike other species, may use alpha4 integrins to traffic to sites of inflammation in vivo.

Animals↗
PubMed1999

Early up-regulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression in rats with hemorrhagic shock and resuscitation.

This study evaluated the effect of resuscitation fluids on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Sprague-Dawley rats (n = 36) were subjected to a 27 mL/kg hemorrhage over 5 min followed by a 1 h shock and 1 h resuscitation. Animals groups included: 1) cannulation only (Sham); 2) hemorrhage only (NR); 3) resuscitation with 1:1 shed blood (Blood); 4) resuscitation with 3:1 lactated Ringer's (81 mL/kg, 3LR+); 5) no hemorrhage but infusion with 3:1 lactated Ringer's (3LR); and 6) resuscitation with .36:1 hypertonic saline (7.5%, 9.7 mL/kg, HTS). At the end of resuscitation, the spleen and lung were harvested for detection of adhesion molecule mRNA and protein by RT-PCR and immunostaining. ICAM-1 and VCAM-1 expression exhibited the following pattern: 3LR+ > HTS approximate to 3LR > Blood approximate to NR approximate to Sham. VCAM-1 mRNA in the lung of the 3LR+ group was 2 or more times more than the groups of Sham, NR, Blood, and 3LR (p < .05). ICAM-1 and VCAM-1 mRNA in the spleen was significantly increased in the 3LR+ group compared with the groups of Sham, NR, and Blood (p < .05). Animals in the 3LR+ group showed enhanced staining for ICAM-1 in the pulmonary microvessels and in the marginal and trabecular areas of the spleen. Pulmonary edema and inflammatory cell infiltration were observed only in the 3LR+ group. In summary, resuscitation with LR following hemorrhagic shock induced immediate up-regulation of ICAM-1 and VCAM-1, which was associated with tissue injury. Thus, the type of resuscitation fluid used affected resuscitation injury.

Animals↗
PubMed2000

mRNA expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in acute renal allograft rejection.

BACKGROUND: The intercellular adhesion molecule-1 (ICAM-1) and the vascular cell adhesion molecule-1 (VCAM-1) show a form of complementary distribution in normal and grafted kidneys. The molecular mechanism by which ICAM-1 and VCAM-1 are increased or induced on vascular cells during acute renal allograft rejection has not been clearly defined. METHODS: We examined ICAM-1 and VCAM-1 mRNA expression in 17 renal allograft biopsies with (n=12) and without (n=5) features of acute rejection, and four control renal biopsies with no detectable abnormalities by RNA in situ hybridization. The expression of ICAM-1 and VCAM-1 protein was also assessed by immunohistochemical staining of frozen sections. RESULTS: In controls and nonrejecting graft biopsies, the signals of the ICAM-1 and VCAM-1 transcripts in vascular cells were almost negligible. Specific signals of ICAM-1 and VCAM-1 mRNAs were detected on the endothelial cells of small muscular arteries in most cases with acute renal allograft rejection. The messages for ICAM-1 and VCAM-1 were also detected on arterial smooth muscle cells in all the five cases with severe type III rejection. CONCLUSIONS: These results suggest that the induced appearance of ICAM-1 and VCAM-1 on the vascular cells of acutely rejecting renal transplants was related to actual cellular synthesis and that both adhesion molecules could act together in the rejection process. They also suggest that the expression of ICAM-1 and VCAM-1 genes by arterial smooth muscle cells may be an important cause of transmural arteritis in severe acute renal allograft rejection.

Acute Disease↗
PubMed1995

Modulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 on human coronary smooth muscle cells by cytokines.

Adhesion molecules have been demonstrated immunohistochemically on smooth muscle cells in atherosclerotic plaques. In endothelial cells cytokines are potent modulators of adhesion molecule expression. We therefore investigated the effects of cytokines on adhesion molecule expression on cultured human coronary and pulmonary smooth muscle cells by cell ELISA and confocal microscopy. Human coronary and pulmonary smooth muscle cells expressed ICAM-1 and VCAM-1 but not E-selectin. ICAM-1 expression was upregulated by TNF alpha, Il-1 beta and IFN-gamma. VCAM-1 expression was increased by TNF alpha and weakly by Il-1 beta, IFN-gamma had no effect on VCAM-1 expression. Cytokine effects on ICAM-1 and VCAM-1 were based on de novo synthesis. These results demonstrate that cytokines regulate ICAM-1 and VCAM-1 expression on human coronary and pulmonary smooth muscle cells. These effects may play an important role in the immune mechanisms in atherosclerosis.

Cells, Cultured↗
PubMed2002

Circulating E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in men with coronary artery disease assessed by angiography and disturbances of carbohydrate metabolism.

It is hypothesized that adhesion molecules could be an early predictor of coronary artery disease. Therefore we investigated the relationship between the concentrations of soluble forms of adhesion molecules and disturbances of glucose metabolism in 78 men referred for coronary angiography but with no previous history of diabetes. The group consisted of 78 men (mean age, 47.6 +/- 7.0 years; mean body mass index [BMI], 28.4 +/- 3.24 with the symptoms of angina pectoris and positive exercise test. All subjects were given a standard oral glucose tolerance test (OGTT) with glucose and insulin estimations. Fasting plasma concentrations of the soluble (s) forms of E-selectin, intercellular adhesion cell molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and HbA(1c) were also measured. According to the OGTT, 10.2% of the patients (n = 8) fulfilled the criteria for type 2 diabetes mellitus and 44.9% (n = 35) for impaired glucose tolerance (IGT). The highest concentrations of sE-selectin were observed in patients with type 2 diabetes mellitus and were significantly higher in comparison to the group with normal glucose tolerance and IGT. The concentration of sVCAM-1 increased with the progression of disturbances of glucose metabolism and remained the highest in type 2 diabetic patients. sICAM-1 concentration was not significantly different. sE-selectin concentration correlated significantly with fasting glucose (r = 0.23, P =.041), postload glucose (r = 0.39, P =.001), and postload insulin (r = 0.28, P =.023). sVCAM-1 was significantly related to the postload glucose concentration (r = 0.30, P =.009). A significant correlation between sICAM-1 concentration and postload insulin was also observed (r = 0.27, P =.025). This would suggest that hyperglycemia increases sE-selectin and sVCAM-1 in plasma, which reflects excessive formation of atherosclerotic plaques in patients with disturbances of glucose metabolism.

Biomarkers↗
PubMed1996

Expression of E-selectin, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 in non-small-cell lung carcinoma.

Vascular cell adhesion molecules (VCAM) play an important part in the regulation of inflammation and are considered to be important in the process of malignant tumour growth. The present study describes the immunohistochemical staining patterns of E-selectin, intercellular adhesion molecule (ICAM)-1 and VCAM-1 on endothelial cells of the vessels in tumour stroma and other cell types in non-small-cell lung carcinoma (NSCLC; n = 43) in association with inflammatory cells. Expression of E-selectin was dominant on endothelial cells in the stromal areas of the tumour, especially at the borders, and was confined to endothelial cells. Moderate to strong staining for ICAM-1 was demonstrated on endothelial cell irrespective of size or localization of the vessels. Compared with ICAM-1, fewer vessels were positive for VCAM-1, and stained with lesser intensity. ICAM-1 expression was demonstrated on NSCLC cells, the basal cells of bronchial epithelium, type II pneumocytes, lymphocytes and fibroblasts. VCAM-1 was clearly expressed on NSCLC cells in 4 of the 43 cases and on lymphocytes and fibroblasts. The staining patterns observed on endothelial cells support the idea of an active status of NSCLC vessels. This phenotypic pattern looks similar to the vascular component of inflammation. The presence of ICAM-1 and VCAM-1 on NSCLC cells suggests a functional role in the process of chemotaxis for tumour cells.

Aged↗
PubMed1995

Porcine vascular cell adhesion molecule (VCAM) mediates endothelial cell adhesion to human T cells. Development of blocking antibodies specific for porcine VCAM.

Vascular cell adhesion molecule (VCAM) is expressed on activated endothelial cells and binds to the alpha 4 beta 1 integrin receptor, very late antigen-4 (VLA-4), expressed on human lymphoid cells. Anti-VCAM mAbs have been shown to prolong allograft survival. To explore the role of porcine VCAM (pVCAM) in xenotransplantation, a recombinant secreted form of pVCAM (spVCAM) was expressed in 293-EBNA cells and purified by metal affinity chromatography. A human lymphoid cell line bound to spVCAM in a VLA-4-dependent manner. Using spVCAM as an immunogen, we developed three anti-pVCAM mAbs that reacted with cell surface pVCAM on porcine aortic endothelial cells (PAEC) but not to human VCAM on human umbilical vein endothelial cells. Pairwise interaction analysis indicated that these mAbs recognized distinct epitopes on pVCAM. Two anti-pVCAM mAbs, 2A2 and 3F4, inhibited the binding of Ramos cells to spVCAM, while the third, 5D11, did not. Similarly, mAbs 2A2 and 3F4 inhibited binding of Ramos cells or human peripheral blood T cells to activated PAEC. The extent of inhibition with mAbs 2A2 and 3F4 was comparable to the inhibition obtained with a blocking mAb to human VLA-4. These anti-pVCAM mAbs will provide a means to specifically block pVCAM in a xenograft setting and allow the determination of the role of pVCAM in a primary xenogeneic immune response.

Amino Acid Sequence↗
PubMed1992

Platelet endothelial cell adhesion molecule, PECAM-1, modulates cell migration.

Cell migration is an important process in such phenomena as growth, development, and wound healing. The control of cell migration is orchestrated in part by cell surface adhesion molecules. These molecules fall into two major categories: those that bind to extracellular matrix and those that bind to adjacent cells. Here, we report on the role of a cell-cell adhesion molecule, platelet-endothelial cell adhesion molecule-1, (PECAM-1), a member of the lg superfamily, in the modulation of cell migration and cell-cell adhesion. PECAM-1 is a 120-130 kDa integral membrane protein that resides on endothelial cells and localizes at sites of cell-cell contact. Since endothelial cells express PECAM-1 constitutively, we studied the effects of PECAM-1 on cell-cell adhesion and migration in a null-cell population. Specifically, we transfected NIH/3T3 cells with the full length PECAM-1 molecule (two independent clones). Transfected cells containing only the neomycin resistance gene, cells expressing a construct coding for the extracellular domain of the molecule, and cells expressing the neu oncogene were used as controls. The PECAM-1 transfectants appeared smaller and more polygonal and tended to grow in clusters. Indirect immunofluorescence of PECAM-1 transfectants showed peripheral staining at sites of cell-cell contact, while the extracellular domain transfectants and the control cells did not. In two quantitative migration assays, the full-length PECAM-1 transfectants migrated more slowly than control cells. Thus, PECAM-1 transfected into a null cell appears to localize to sites of cell-cell contact, promote cell-cell adhesion, and diminish the rate of migration. These findings suggest a role for this cell-cell adhesion molecule in the process of endothelial cell migration.

Animals↗
PubMed1997

Advanced glycosylated end products activate the functions of cell adhesion molecules on lymphoid cells.

It has been proposed that advanced glycosylated end products (AGEs) are involved in the pathogenesis of vascular damages in both type 1 and type 2 diabetes. Furthermore, it has been assumed that AGEs cause an alteration of both expression and activity of cell adhesion molecules which are responsible for migration of circulating cells through the endothelial layer of the vessels. The effect of AGEs on the activity of cell adhesion molecules was studied in our experiments using the homotypic adhesion assay, specific monoclonal antibodies and lymphoid cell lines. It was shown that proteins glycosylated in vitro seemed to increase the percentage of homotypic aggregation of lymphoid cells. This effect was mediated via the interaction between LFA-1 and ICAM-1 which was demonstrated by the fact that specific monoclonal antibodies against these cell adhesion molecules could block the effect of the AGEs. The results obtained reveal that the advanced glycosylated end products activate the function of cell adhesion molecules on lymphoid cells. It can be speculated that the activation of cell adhesion molecules might enhance the direct cellular contacts between the lymphoid cells in the immune response. Moreover, the effect of AGEs might be responsible for an enhanced adhesion of monocytes to endothelial cells and their migration through the vessel wall.

Antibodies, Monoclonal↗
PubMed2002

p38 kinase and c-Jun N-terminal kinase oppositely regulates tumor necrosis factor alpha-induced vascular cell adhesion molecule-1 expression and cell adhesion in chondrosarcoma cells.

We investigated signaling pathways leading to tumor necrosis factor (TNF) alpha-induced intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 expression in chondrosarcoma cells, and determined the functional significance of their expression by examining Jurkat T cell adhesion. TNFalpha induced VCAM-1 and ICAM-1 expression and Jurkat T cell binding. Antibody blocking assay indicated that VCAM-1 mediates TNFalpha-induced Jurkat T cell adhesion. TNFalpha caused activation of mitogen-activated protein (MAP) kinase subtypes, extracellular signal-regulated protein kinase, p38 kinase, and c-jun N-terminal kinase (JNK). ICAM-1 expression was not altered by the inhibition of MAP kinases. However, VCAM-1 expression and Jurkat T cell adhesion was blocked by the inhibition of p38 kinase, whereas inhibition of JNK enhanced VCAM-1 expression and cell adhesion without any modulation of NFkappaB activation. Our results, therefore, indicate that p38 kinase mediates TNFalpha-induced VCAM-1 expression and cell adhesion, whereas JNK suppresses VCAM-1 expression that is independent to NFkappaB activation.

Blotting, Western↗
PubMed1992

Cell adhesion molecules as targets for Hox genes: neural cell adhesion molecule promoter activity is modulated by cotransfection with Hox-2.5 and -2.4.

In an effort to determine whether homeobox genes modulate the activity of the promoter of the mouse neural cell adhesion molecule (N-CAM) gene, we have carried out a series of cotransfection experiments using NIH 3T3 cells. Plasmids were constructed containing Xenopus laevis Hox-2.5 and -2.4 coding sequences linked to a human cytomegalovirus promoter (CMV-Hox-2.5 and CMV-Hox-2.4). A 4.9-kilobase DNA fragment containing 5' flanking and first exon sequences of the mouse N-CAM gene was linked to a chloramphenicol acetyltransferase (CAT) reporter gene (N-CAM-Pro-CAT). Cotransfection with CMV-Hox-2.5 and N-CAM-Pro-CAT resulted in a strong induction of CAT activity. The N-CAM promoter contained two potential homeodomain binding sites (sites I and II) within a 47-base-pair segment (512-559 base pairs upstream of the ATG codon in the first exon of the N-CAM gene). This segment was linked to a minimal promoter (simian virus 40 early) and a downstream CAT gene. Although this construct was transcriptionally active at a low level in NIH 3T3 cells, cotransfection of CMV-Hox-2.5 resulted in CAT activity that was greatly elevated. Mutational studies revealed that it was the homeodomain binding site II sequence that was required for this regulation. In contrast, cotransfection with CMV-Hox-2.4 eliminated the CAT activity that was driven by the CMV-Hox-2.5 construct. Thus, the products of two related Hox genes, which are located adjacent to each other in the Hox-2 complex, can differentially modulate transcription from the promoter of a cell adhesion molecule gene. The results suggest that the N-CAM gene is likely to be a target for regulation by Hox gene products.

3T3 Cells↗
PubMed1993

The epidermal growth factor/cAMP-inducible ectoCa(2+)-ATPase of human hepatoma Li-7A cells is similar to rat liver ectoATPase/hepatocyte cell adhesion molecule (cell-CAM 105).

Human hepatoma Li-7A cells exhibit two cell surface ATPase (ectoATPase) activities distinguishable by their different biochemical properties. The activity of the minor ectoATPase, ectoCa(2+)-ATPase, is enhanced severalfold when Li-7A cells are treated simultaneously by epidermal growth factor (EGF) and cAMP elevating agents (Knowles, A. F., 1990, Arch. Biochem. Biophys. 283, 114-119). Here we report that the human ectoCa(2+)-ATPase is biochemically similar to the major rat hepatocyte ectoATPase/cell adhesion molecule (cell-CAM 105) with respect to response to divalent ions and sulfhydryl reagents. Furthermore, the binding of rat liver ectoATPase antibody increased markedly in EGF/cholera toxin/hydrocortisone-treated Li-7A cells compared to untreated cells. Western blot analysis revealed cross-reactivity of the antibody with a 125-kDa protein. Partial purification of ectoCa(2+)-ATPase from EGF/cholera toxin/hydrocortisone-treated Li-7A cells confirmed that enrichment of the 125-kDa protein correlated with an increase in ATPase activity. We conclude that EGF and increased levels of cAMP lead to increased synthesis of the ectoCa(2+)-ATPase in Li-7A cells. The present demonstration of similarity between the ectoCa(2+)-ATPase and a rat liver cell adhesion molecule, cell-CAM 105, contributes significantly to an understanding of the implication of down-regulation of ectoCa(2+)-ATPase during hepatocyte-hepatoma transformation.

Adenosine Triphosphatases↗
PubMed2000

Interferon-gamma up-regulates intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 and recruits lymphocytes into the vagina of immune mice challenged with herpes simplex virus-2.

Lymphocyte recruitment into tissues involves interactions between adhesion molecules on vascular endothelial cells and corresponding ligands on the lymphocyte surface. In the present study we investigated the expression of four endothelial addressins in the vagina and their possible up-regulation by interferon-gamma (IFN-gamma) in immune mice after vaginal challenge with herpes simplex virus type 2. The adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were minimally expressed in the vagina of non-immune mice with or without vaginal challenge and in immune mice before challenge, but both were up-regulated by IFN-gamma, directly or indirectly, in immune mice after challenge. Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) was detected in most vaginas but was not up-regulated by IFN-gamma in immune mice after virus challenge. E-selectin was not detected in any vaginas. The results suggest that ICAM-1 and VCAM-1 may be involved in rapid, IFN-gamma-mediated recruitment of lymphocytes to the vaginal mucosal of immune mice after local virus challenge.

Animals↗
PubMed2000

Effects of UVB radiation on cytokine generation, cell adhesion molecules, and cell activation markers in T-lymphocytes and peripheral blood HPCs.

BACKGROUND: Immunomodulatory effects of UV light have increasingly become a focus in transfusion medicine, BMT and transplantation immunology. In the transplant setting, the use of UVB radiation may reduce or abolish T-cell activation without compromising either bone marrow (BM) engraftment or graft-versus-leukemia effect. In this study, BM and apheresis-derived peripheral blood HPCs were used to investigate the effects of UVB on colony-forming ability, CD34+ cell viability, and growth potential, as well as on the secretion of MNC cytokines and the expression of cell surface markers and adhesion molecules. STUDY DESIGN AND METHODS: After UVB radiation, enriched populations of T cells and antigen-presenting cells (APCs) were treated with PHA, and the MNC response was measured, as was colony-forming ability. CD34+ cells were quantified and their growth potential was determined in culture. Next, T-cell activation status, cell adhesion molecule and cell surface activation marker expression, and cytokine profiles were evaluated, and cytokine mRNA was quantitated. Parallel studies were done in unirradiated control cell populations. RESULTS: Low-dose (10 mJ/cm(2)) UVB mitigates MNC proliferative responses by 94 percent while maintaining 60 and 80 percent of colony-forming ability in peripheral blood HPC and BM preparations, respectively, and >50 percent of colony-forming ability in CD34+ cell-enriched samples. Low-dose UVB radiation also significantly reduces T-cell production of TNFalpha, TNFalpha mRNA, TNFbeta, IL-2, and IL-6 and downregulates T-cell expression of CD28, CD25, CD69, and intercellular adhesion molecule 1. CONCLUSION: These findings have shown that a "window" of low-dose UVB radiation (10 mJ/cm(2)) exists, at which BM- and peripheral blood-derived MNC proliferation is inactivated, while the HPCs are relatively spared. UVB light selectively affects T cells, while APCs are resistant to low doses of UVB. UVB radiation also alters the expression of some cell surface markers and cytokines that are important in T-cell activation pathways. Reduction of T-cell activation without cytocidal effect may allow UVB radiation to become an immunomodulating agent in BM or HPC transplantation.

Antigen-Presenting Cells↗
PubMed2004

[Expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in the pig coronary artery injury model: comparison of plain old balloon angioplasty and stent implantation].

OBJECTIVES: Restenosis after coronary intervention usually occurs due to coronary remodeling or neointimal formation, but inflammation is also important especially after stent implantation. Adhesion molecules are important in the recruitment of inflammatory cells into the neointima and in the phenotypical changes of vascular smooth muscle cells. To examine the role of adhesion molecules in the pathogenesis of restenosis, immunohistochemical expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was investigated in the pig coronary injury model. METHODS: Left anterior descending coronary arteries of pigs were injured using a balloon. Two weeks after the injury, balloon injury was performed again in the balloon group and a Palmaz-Schatz stent was implanted in the stent group. Pigs were sacrificed at 1, 2 and 4 weeks. Immunohistochemical analysis was performed using ICAM-1, VCAM-1, macrophage and alpha-smooth muscle actin antibodies. RESULTS: In non-injured vessels, weak immunoreactivities of ICAM-1 and VCAM-1 were observed in the endothelium and media. In injured sites, ICAM-1 and VCAM-1 were found in the inflammatory cells and smooth muscle cells in the neointima from 1 week, and strong immunoreactivities were seen around the strut in the stent group. Although the immunoreactivities peaked at 2 weeks in the balloon group, strong immunoreactivities were still seen at 4 weeks in the stent group. Regenerated endothelial cells were positive for both antibodies from 2 weeks. CONCLUSIONS: The expression of ICAM-1 and VCAM-1 lasted longer in the stent group than in the balloon group, suggesting the occurrence of late restenosis after stent implantation. Control of the inflammatory response including adhesion molecules is essential for further reduction of restenosis after stent implantation.

Angioplasty, Balloon, Coronary↗
PubMed1999

Interleukin-8, interleukin-10, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression levels are higher in synovial tissue from patients with rheumatoid arthritis than in osteoarthritis.

The aim of this work was to determine differences in pro- and anti-inflammatory cytokine and adhesion molecule expression in synovial tissue from patients with rheumatoid arthritis (RA) or osteoarthritis (OA). Synovial tissue samples were obtained from patients with RA and OA, and from healthy individuals. The expression of mRNA of interleukin (IL)-1beta, IL-4, IL-6, IL-8, IL-10, IL-13, tumour necrosis factor-alpha (TNF-alpha) and transforming growth-factor-beta1 (TGF-beta1) was evaluated by the polymerase chain reaction (PCR). In addition, IL-8 and IL-10 transcripts were measured by quantitative PCR. The expression of IL-8 and IL-10 proteins was determined by immunoperoxidase staining. To evaluate the inflammatory stage of synovial tissue, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) protein expression was also determined. RA patients were found to display higher levels of adhesion molecules than patients with OA. PCR analysis showed a similar profile of cytokine transcripts between the OA and RA groups. Gene expression of IL-4 and IL-13 in synovium was undetectable. In contrast, IL-1beta, IL-6, IL-8, IL-10, TNF-alpha and TGF-beta1 transcripts were expressed by both groups. Increased levels of IL-8 and IL-10 transcripts and their proteins were observed in synovium from RA patients when compared to patients with OA and healthy controls. Thus, our data show that IL-8, IL-10, ICAM-1 and VCAM-1 expression levels are higher in synovial tissue from patients with RA than in similar tissue from patients with OA.

Adult↗
PubMed1993

Nickel chloride and cobalt chloride, two common contact sensitizers, directly induce expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule (ELAM-1) by endothelial cells.

Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1, E-selectin) are endothelial surface molecules that play a role for leukocyte recruitment to sites of inflammation, e.g., during contact hypersensitivity. We studied the effects of sensitizing agents (2,4-dinitro-benzenesulfonic acid, metal salt haptens) and chemically related substances on endothelial adhesion molecule expression. Using flow cytometry and an enzyme-linked immunosorbent assay, NiCl2 and, to a lesser extent, CoCl2 were found to up-regulate ICAM-1, VCAM-1, and ELAM-1 expression on cultured human umbilical vein endothelium whereas the other substances tested showed no effects. Induction of adhesion molecules by NiCl2 required de novo mRNA and protein synthesis. Up-regulation could be blocked by kinase inhibitor H-7 but not staurosporine, suggesting involvement of phosphorylation events independent of protein kinase C activation. Concomitant application of NiCl2 and neutralizing antibodies to IL-1 did not block up-regulation by the hapten demonstrating that the latter did not act via an IL-1-dependent autocrine mechanism. Regarding ELAM-1 induction, pre-treatment for 24 h with NiCl2 produced hyporesponsiveness to IL-1 and TNF-alpha upon restimulation, suggesting that NiCl2 and these cytokines may partially share a common pathway of activation. In addition, analysis of cultured foreskin specimens revealed that NiCl2 may induce up-regulation of ELAM-1 on microvascular endothelium in vivo. Our data demonstrate that both Ni++ and Co++ to which simultaneous contact sensitivity is frequently observed have the ability to directly up-regulate endothelial adhesion molecules. This shared property may represent an adjuvant mechanism that promotes sensitization and elicitation events in contact hypersensitivity to these haptens.

Capillaries↗