Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In chronic inflammatory conditions, mononuclear cells infiltrate the involved connective tissue and may persist, perhaps because of binding to adhesion molecules on connective tissue cells, as well as extracellular matrix. Here we investigated whether vascular cell adhesion molecule-1 (VCAM-1) may be induced on human dermal fibroblasts by proinflammatory cytokines. Expression of VCAM-1 was determined by Northern blotting, cell enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Only trace amounts of VCAM-1 mRNA or protein were constitutively expressed on dermal fibroblasts but both were rapidly (within 4 hr) upregulated by tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha) and somewhat slower (20 hr) by interferon-gamma (IFN-gamma). The combination of TNF-alpha and IFN-gamma had at least an additive effect. The adhesion function of the expressed VCAM-1 was examined by studying the adhesion of the Jurkat T lymphocytes to fibroblasts. Adhesion of Jurkat cells to dermal fibroblasts was markedly increased by stimulation of fibroblasts with TNF-alpha and IFN-gamma (22% of cells adhered versus 9% on unstimulated fibroblasts). The increased adhesion was inhibited to that on unstimulated fibroblasts by monoclonal antibody (mAb) to domain 1 of VCAM-1, but not by mAb to domain 4. MAb to very late antigen-4 (VLA-4), the integrin counter-receptor on lymphocytes for VCAM-1, completely inhibited the increase in Jurkat cell adhesion to activated fibroblasts and partly also inhibited basal adhesion to unstimulated fibroblasts. These results suggest that VCAM-1 expression by dermal fibroblasts is inducible at the mRNA, protein and functional levels by proinflammatory cytokines. The VLA-4/VCAM-1 pathway maybe involved in adhesive interactions between T lymphocytes and activated fibroblasts in the skin during chronic dermal inflammatory conditions.
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PMID:Expression of VCAM-1 and VLA-4 dependent T-lymphocyte adhesion to dermal fibroblasts stimulated with proinflammatory cytokines. 895 50

Coal workers' pneumoconiosis (CWP) is characterized by a chronic inflammatory lung reaction associated with macrophage accumulation in alveolar spaces. In this study, we investigated in CWP the implication of adhesion molecules such as E-selectin, ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1) and the role of TNF-alpha which is one of the cytokines inducing their expression. Adhesion molecule expression was analysed by immunohistochemistry on lung biopsies from patients with CWP and from healthy subjects. In parallel, soluble adhesion molecules were detected in bronchoalveolar lavage fluids (BALF) from patients by specific ELISA. The involvement of TNF in the induction of these adhesion molecules was measured (i) by immunohistochemistry on sections from lung fragments, and (ii) by evaluating in vitro the expression of adhesion molecules on endothelial cells and on alveolar epithelial cells in the presence of alveolar macrophage supernatants. In control subjects, a weak staining of ICAM-1 was detected only in alveolar walls, while E-selectin and VCAM-1 were undetectable. In pneumoconiotic patients, ICAM-1 was expressed at a high level by endothelium, by alveolar and bronchial epithelial cells and by alveolar macrophages. E-selectin and VCAM-1 expression remained undetectable. Measurement of soluble adhesion molecule showed that only the concentration of sICAM-1 was significantly increased in BALF from patients with CWP compared with controls. The involvement of TNF in this ICAM-1 expression was shown by the in vitro effect of alveolar macrophage supernatants on adhesion molecule expression by endothelial cells and epithelial cells (this effect was neutralized by anti-TNF antibodies) and by the increased production of TNF in the lung of pneumoconiotic patients. These data provide evidence for the involvement of ICAM-1, induced at least in part by alveolar macrophage-derived TNF, in the development of the inflammatory reaction in CWP.
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PMID:Expression of leucocyte-endothelial adhesion molecules is limited to intercellular adhesion molecule-1 (ICAM-1) in the lung of pneumoconiotic patients: role of tumour necrosis factor-alpha (TNF-alpha). 897 25

All trans-retinoic acid (ATRA) induces complete remission in acute-promyelocytic-leukemia (APL) patients. This study investigated the adhesive properties of APL cells for the endothelium and the extracellular matrix, their motility and the effect of ATRA on these functions. Blasts from 7 APL patients adhered to resting and IL-1-activated endothelium, to the same degree as normal PMN. Adhesion was partially mediated by ICAM-1 and, for IL-1-activated endothelium, by VCAM-1 and E-selectin. These cells showed less adhesiveness for the matrix than PMN, although they maintained the same substrate preference: they adhered to fibronectin and thrombospondin, but not to laminin and type-IV collagen. Exposure to ATRA in vitro (1 microM for 48 to 96 hr) increased the adhesiveness of APL cells; this effect was particularly evident in the case of sub-endothelial matrix and fibronectin. A similar increment in adhesiveness was observed when comparing cells from 2 patients before and after treatment with ATRA. APL cells migrated in response to fMLP and motility was increased by ATRA. In conclusion, APL cells were less adhesive to the matrix than PMN, but treatment with ATRA considerably enhanced their adhesive properties. This could be important in determining the efflux of leukemic cells from the bone marrow and their tissue infiltration during ATRA therapy.
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PMID:Effect of all trans-retinoic acid (ATRA) on the adhesive and motility properties of acute promyelocytic leukemia cells. 898 93

This study examined the adhesive interactions of peripheral blood B cells with TNF-alpha-activated endothelial monolayers, and analyzed the roles of E-selectin, P-selectin, or VCAM-1 molecules expressed on activated HUVEC. B cell interaction occurred on activated HUVEC, but not on resting HUVEC under flow conditions. The majority of peripheral blood B cells expressed P-selectin glycoprotein ligand-1 and alpha4 integrin. However, the expression of cutaneous lymphocyte Ag on B cells was low. Under flow conditions, B cells could bind to P-selectin-coated tubes and VCAM-1-transfected Chinese hamster ovary cells. In contrast, B cells could not bind to E-selectin-coated tubes. Adhesion activity of B cells to P-selectin-coated tubes was weaker than that of T cells. Furthermore, adhesion activity of B cells to VCAM-1-transfected Chinese hamster ovary cells was similar to that of T cells. Treatment of activated HUVEC with anti-VCAM-1 mAb reduced interaction of B cells under flow conditions. However, the treatment of activated HUVEC with anti-P-selectin mAb did not reduce interaction. These data indicated that the interaction of VCAM-1 with alpha4 integrin plays a major role in an initial attachment of B cells to endothelial monolayers under flow conditions.
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PMID:Analysis of initial attachment of B cells to endothelial cells under flow conditions. 899 86

Adhesion molecule expression may become useful in monitoring cardiac graft rejection, but first the question of whether expression is upregulated by cytomegalovirus (CMV), a common post-transplant infection, must be answered. To study this, all cardiac biopsies (n = 201) on 12 cardiac transplant recipients were examined for rejection grade and VCAM-1, ICAM-1, and E-selectin expression over the first 6-15 months post-transplant. Adhesion molecule expression in biopsies taken during documented CMV infections were compared to those taken in the absence of infection, both overall and sorted as to rejection grade. There were 17 CMV infections in this patient group. VCAM-1 was expressed in 82% of biopsies coincident with CMV infections, compared to 43% of biopsies unrelated to CMV infection, a significant difference (p < 0.01). E-selectin was expressed in 65% of biopsies with CMV infection, compared to 30% of biopsies unrelated to CMV infection, also statistically significant (p = 0.01). Both VCAM-1 and E-selectin were expressed in 80% of biopsies without rejection taken during CMV infections, significantly greater than the 24% incidence of VCAM-1 and 14% incidence of E-selectin expression in biopsies without rejection that were not concomitant with CMV infection. In the absence of CMV infection, both VCAM-1 and E-selectin expression correlated significantly with rejection grade, but this relationship became invalid in the presence of CMV infection. ICAM-1 expression bore no relation to CMV infection. VCAM-1 and E-selectin expression in cardiac biopsies can be upregulated with CMV infection in the absence of graft rejection.
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PMID:VCAM-1 and E-selectin expression during cytomegalovirus infection in post-transplant myocardial biopsies. 899 74

Bacterial heat shock proteins (HSPs) from Escherichia coli (GroES, GroEL, and DNAk) were tested for their ability to induce by themselves the expression and release of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and granulocyte-monocyte colony-stimulating factor (GM-CSF) by human monocytes and GM-CSF, IL-6, E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) by human umbilical vein endothelial cells (HUVEC). Our study demonstrated that treatment of monocytes with DNAk increased IL-6, TNF-alpha, and GM-CSF release in a dose-dependent manner. The same effect was elicited by GroEL but at a lower rate. Treatment of HUVEC cultures with DNAk and GroEL also increased GM-CSF, IL-6, E-selectin, ICAM-1, and VCAM-1 release in a dose-dependent fashion. In any case, the greatest release was obtained by using DNAk and GroEL at a concentration of 1 microg/ml. DNAk and GroEL were also able to up-regulate the surface expression of E-selectin, ICAM-1, and VCAM-1. As detected by reverse transcription-PCR analysis, DNAk and GroEL also increased the steady-state levels of cytokines and adhesion molecules in human monocytes and endothelial cells. In our study GroES showed a significant activity only on the release, surface expression, and mRNA transcription of E-selectin. Adhesion molecule expression seems to be a direct effect of HSPs and not via cytokines. Furthermore, these effects are due to HSPs properties because they are inhibited by specific monoclonal antibodies. These findings support the potential role of HSPs in modulating cell interactions during immunological and inflammatory responses.
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PMID:Cytokine and adhesion molecule expression in human monocytes and endothelial cells stimulated with bacterial heat shock proteins. 900 33

Human acute myeloid leukemia (AML) cells adhere to bone marrow fibroblasts (BMF) and extracellular matrix proteins including fibronectin. Adhesion is increased when fibroblast monolayers are exposed to tumor necrosis factor-alpha (TNF) alone and in combination with interferon-gamma (IFN) or interleukin-4 (IL-4). The combination of TNF and IFN caused enhanced AML cell adhesion to treated BMFs, from a mean of 25.0 +/- 4.1% to 36.3 +/- 5.4% (p = 0.0007). Enhanced binding was partially a result of upregulated vascular cell adhesion molecule-1 expression on BMFs. Intercellular adhesion molecule-1 was also upregulated, but did not appear to play a role in the increased binding to cytokine-stimulated BMFs. In contrast to observed adhesion to resting BMFs, AML cells binding to TNF/IFN-stimulated BMFs rely more heavily on the VLA-4 alpha chain (CD49d). In some cases, alpha4 integrin chain antibody was more effective than beta1 antibody in blocking binding, suggesting that a non-beta1 alpha4 integrin, possibly alpha4 beta7, on AML cells may act as a stromal ligand. The addition of alpha4 antibody to beta1 and beta2 antibodies significantly increased the inhibition of AML cells to stimulated BMFs. The myeloid cytokines granulocyte colony stimulating factor, granulocyte-monocyte colony stimulating factor, interleukin-3 and stem cell factor enhanced the adhesion of AML blast cells to BMFs in some cases. The phorbol ester PMA, however, consistently upregulated AML cell-binding to BMFs, the increase being mediated entirely via beta1 and beta2 integrins without altering AML cell integrin expression. Binding of AML cells to marrow stroma can be enhanced by influences on leukemic cell or stroma. Enhanced binding under these conditions occurs via different pathways, illustrating the heterogeneity of mechanisms underlying leukemic cell retention within the bone marrow stroma.
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PMID:Bone marrow fibroblast exposure to the inflammatory cytokines tumor necrosis factor-alpha and interferon-gamma increases adhesion of acute myeloid leukemia cells and alters the adhesive mechanism. 901 13

Rats receiving a single dose (10 mg/l00 g body wt) of PAN develop severe proteinuria and acute interstitial nephritis. To investigate the mechanisms involved in interstitial leucocyte accumulation, we examined the expression of adhesion molecules on kidney tissue sections as well as on endothelial cell cultures. We also performed in vivo treatments with antibodies against adhesion molecules. Enhanced expression of intercellular adhesion molecule-1 (ICAM-1) was found on day 7 of the disease, when interstitial nephritis was first detected. Also, rat endothelial cells in culture showed maximal expression of ICAM-1 in the presence of 10(-9) - 10(-11) M PAN. Adhesion of peripheral blood mononuclear cells (PBMC) on kidney sections from PAN-treated rats was highest on day 7 (3.05 +/- 0.7 (mean +/- s.e.m.); controls 0.75 +/- 0.5). Such increased adhesion was notably blocked after PAN-treated rat kidney sections were incubated with anti-ICAM-1 MoAb (0.9 +/- 0.4). In addition, adhesiveness of PBMC to PAN-stimulated endothelial cells in culture was enhanced (25 +/- 2.5%; non-stimulated cells 13 +/- 3.1%). The addition of specific MoAbs against ICAM-1 and lymphocyte function-associated antigen-1 (LFA-1) produced a high blockage of adhesiveness induced by exposure to PAN (inhibition 58 +/- 3%; non-stimulated cells 40 +/- 7%). Simultaneous administration to PAN-treated rats of anti-LFA-1 and anti-ICAM-1 MoAbs reduced the number of interstitial cells by 70% compared with the 30% of reduction obtained when anti-very late antigen-4 (VLA-4) MoAb and anti-vascular cell adhesion molecule-1 (VCAM-1) antibodies were used. Our results suggest that the LFA-1/ICAM-1 pathway plays a principal role in the interstitial nephritis occurring in rats with PAN-nephrosis.
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PMID:Role of leucocyte adhesion molecules in aminonucleoside of puromycin (PAN)-associated interstitial nephritis. 909 15

This study examines the molecular mechanisms that underlie the observed preferential interactions of memory vs naive T cells with activated vascular endothelium. Many more CD4+ CD45RO+ (memory) cells adhered to 6-h TNF-alpha-activated human umbilical vein endothelium under flow than CD4+CD45RA+ (naive) cells. Adhesion studies were performed using Chinese hamster ovary (CHO) cell monolayers expressing human E- or P-selectin (CHO-E and CHO-P, respectively) or with soluble vascular cell adhesion molecule-1 (VCAM-1)-coated glass surfaces. Under flow at 1.8 dynes/cm2, RO+ T cells rolled extensively at low velocity on both CHO-P and CHO-E monolayers and VCAM-1, whereas very few RA+ T cells interacted with these surfaces. VCAM-1-dependent rolling was blocked completely by anti-very late Ag-4 (VLA-4) Abs. Purified CD4+RA+ T cells could be converted to RO+ cells by mitogen stimulation and 7-day culture in vitro, and this correlated with the acquisition of the ability to roll on E- or P-selectin, but not on VCAM-1 under flow. In summary, these data indicate that CD45RO+ cells interact with E- and P-selectins and VCAM-1 much more effectively than do CD45RA+ cells under flow conditions, and these adhesion pathways may contribute, either individually or in combination, to the preferential recruitment of memory T cells to peripheral sites of inflammation.
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PMID:CD45RA-RO+ (memory) but not CD45RA+RO- (naive) T cells roll efficiently on E- and P-selectin and vascular cell adhesion molecule-1 under flow. 910 26

These experiments were designed to study the increased sensitivity of pregnant rats to endotoxin. Pregnant (Pr), cyclic (C), and progesterone (P)-treated pseudopregnant rats with or without a decidualized uterus (PSP and DEC rats, respectively) received infusions of an ultra-low dose of endotoxin (1.0 microg/kg BW) and were killed 3 days later. Pr, PSP, and DEC rats were infused on Day 14, C rats on diestrus. Endotoxin-infused rats were compared with saline-infused rats in the same reproductive conditions. The inflammatory reaction of the glomeruli of the kidneys was studied by immunohistochemical methods using 4-microm cryostat sections stained with specific monoclonal antibodies against neutrophils (polymorphonuclear cells, PMNs) and monocytes (MOs), and against the adhesion molecules ICAM-1 and VCAM-1 on the endothelium, and LFA-1, MAC-1, and VLA-4 on the leukocytes. Endotoxin infusion increased glomerular PMN and MO number in Pr, PSP, and DEC rats, all of which have elevated P levels, but not in C rats, which do not. The endotoxin-induced expression of adhesion molecules, associated with this influx of inflammatory cells, varied with the reproductive condition. In C rats there was no increased adhesion molecule expression after endotoxin treatment, in Pr rats there was increased expression of both the combinations ICAM-1/LFA-1 and VCAM-1/VLA-4. DEC rats did not express either of these combinations (although there was expression of ICAM-1); PSP rats expressed the combination ICAM-1/MAC-1. Adhesion molecule expression thus seems to be regulated by ovarian (e.g., P) and placental factors (e.g., of trophoblastic and decidual origin). Because the different combinations of adhesion molecules in the various reproductive conditions after exposure to endotoxin led to more or less the same leukocyte influx under these conditions, the increased sensitivity to endotoxin of pregnant individuals cannot be reduced to differences in leukocyte influx into the glomeruli.
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PMID:Reproductive condition and the low-dose endotoxin-induced inflammatory response in rats. Glomerular influx of inflammatory cells and expression of adhesion molecules. 916 91


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