Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accumulating evidence supports the importance of leukocyte-endothelial cell adhesion molecule (CAM) expression as an initiating process in tissue inflammation. To investigate the relevance of CAM expression to allergic airways inflammation, nasal biopsies from patients with perennial allergic rhinitis (n = 8) and from nonatopic healthy volunteers (n = 8) were immunostained with monoclonal antibodies directed against the CAMs, intercellular adhesion molecule-1 (ICAM-1), endothelial cell adhesion molecule-1 (ELAM-1), and vascular cell adhesion molecule-1 (VCAM-1). The endothelial staining of these CAMs was related to the number of vessels within each biopsy, delineated by a monoclonal antibody against Ulex europaeus-1 lectin bound to endothelial cells, and to the number of tissue leukocytes staining for one of the ligands of ICAM-1, the beta 2 integrin, lymphocyte function-associated antigen (LFA-1). Expression of CAMs was related to the number of infiltrating neutrophils, eosinophils, and lymphocytes identified immunohistochemically within the biopsies. ICAM-1 was the most prominent CAM present on the endothelium of the normal nasal mucosa, with less expression of ELAM-1 and only minimal or absent expression of VCAM-1. In perennial rhinitis, both ICAM-1 (P less than 0.05) and VCAM-1 (P less than 0.01) expression on endothelial cells were increased and were positively correlated in their level of expression (P less than 0.002). The number of tissue LFA-1-positive cells was significantly greater (P less than 0.05) in the biopsies from the perennial rhinitics (median, 27.3/mm2) than from the healthy controls (median, 5.3 cells/mm2). LFA-1 expression significantly correlated with the number of ICAM-1-positive vessels (P less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 Oct
PMID:The expression of leukocyte-endothelial adhesion molecules is increased in perennial allergic rhinitis. 138 78

Cultured human umbilical vein endothelial cell (EC) monolayers stimulated with 10 ng/ml tumor necrosis factor demonstrate a time-dependent increase in the expression of the vascular cell adhesion molecule-1 (VCAM-1) with maintained maximal expression at 24 h following EC activation. A monoclonal antibody (mAb) directed against VCAM-1 (1G11) significantly inhibited the adhesion of eosinophils, but not neutrophils, to EC, which had been activated by tumor necrosis factor-alpha for 24 h, but only when eosinophils had been pretreated with an mAb directed against the common beta chain of the CD11/CD18 complex. In the absence of pretreatment with anti-CD18, mAb 1G11 had no significant effect on eosinophil adhesion. These results suggest that eosinophils bind to VCAM-1. However, the functional capacity in this model of the eosinophil receptor for VCAM-1 is likely to be minor compared with the activity of the CD11/CD18 leukocyte adhesion molecules.
Am J Respir Cell Mol Biol 1991 Nov
PMID:Vascular cell adhesion molecule-1 and eosinophil adhesion to cultured human umbilical vein endothelial cells in vitro. 171 36

This review will discuss a number of specific cell adhesion molecules present on the surface of endothelial and epithelial cells in the lung. Molecules such as integrins, proteoglycans, and the hyaluronic acid receptor, CD44, are found on the abluminal or basement membrane side of the cell and function as cell-substratum receptors. Cadherins, integrins, and platelet-endothelial cell adhesion molecule-1 (PECAM-1) are present at the cell-cell borders of adjacent endothelial and/or epithelial cells and function to initiate or maintain cell-cell adhesion. Finally, a number of inducible cell adhesion molecules such as endothelial-leukocyte adhesion molecule-1 (ELAM-1), granule-associated membrane protein 140 (GMP140), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) are expressed on the luminal surfaces of these cells during inflammation and function as cell-cell adhesion molecules important in white blood cell, platelet, or tumor cell adhesion. These adhesion molecules likely play important roles in maintaining the normal structure and function of the lung, as well as participating in pulmonary processes such as inflammation, wound healing, and the development and spread of malignant disease.
Am J Respir Cell Mol Biol 1991 Mar
PMID:Endothelial and epithelial cell adhesion molecules. 200 Dec 88

Epithelial damage in the airways is a feature often observed in patients with asthma and is probably caused by the interaction of epithelial cells with leukocytes. As adhesion molecules are thought to be important in this interaction, we analyzed the expression and modulation of adhesion molecules on primary cultured human bronchial epithelial cells and the bronchial epithelial cell lines BEAS-2B and NCI-H292. E-selectin, P-selectin, and VCAM-1 were absent under basal and stimulated conditions. The adhesion molecules ICAM-1 (CD54), LFA-3 (CD58), and CD44 (H-CAM) were expressed basally on primary cultured human bronchial epithelial cells and the BEAS-2B and NCI-H292 cell lines. CD44 and LFA-3 expression did not change after stimulation with IFN-gamma or TNF-alpha. In contrast, ICAM-1 expression on human bronchial epithelial cells and BEAS-2B cells could be increased by incubation with PMA, IFN-gamma, TNF-alpha, and especially with the combination of IFN-gamma and TNF-alpha. The maximal ICAM-1 expression on both epithelial cell types was obtained with the combination of TNF-alpha and IFN-gamma after 48 h of incubation. The NCI-H292 cell line was different in that it only showed increased ICAM-1 expression after stimulation with PMA and IFN-gamma and not by the combination of IFN-gamma and TNF-alpha or with TNF-alpha alone. In conclusion, the bronchial epithelial cells tested express several adhesion molecules, but only ICAM-1 expression was influenced by inflammatory cytokines.
Am J Respir Cell Mol Biol 1993 Dec
PMID:Expression and modulation of adhesion molecules on human bronchial epithelial cells. 750 27

We examined whether antirheumatic drugs alter cytokine- or lipopolysaccharide-induced expression of adhesion molecules on vascular endothelial cells. Human umbilical cord vein endothelial cells were co-cultured with various antirheumatic drugs in the presence of inflammatory cytokines, and adhesion molecule expression was measured by cell enzyme-linked immunosorbent assay and Northern blot analysis. Among these antirheumatic drugs, gold sodium thiomalate significantly inhibited intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression on vascular endothelial cells and suppressed cellular binding between human monocytic cell lines, including U937 and HL-60 cells, and interleukin-1 beta-stimulated vascular endothelial cells. It is speculated that down-regulation of adhesion molecules might be one of the novel mechanisms of action of gold sodium thiomalate.
Mol Pharmacol 1994 Oct
PMID:Gold sodium thiomalate down-regulates intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression on vascular endothelial cells. 752 48

Eosinophils play a critical role in the pathogenesis of bronchial asthma by releasing various mediators. To understand the mechanisms of eosinophil migration to the site of inflammation, we examined the expression of adhesion molecules in the bronchial tissues of asthmatic subjects with air flow limitation. By immunohistochemical analysis, Mac-1, LFA-1, and VLA-4 were strongly positive in eosinophils and mononuclear cells infiltrated in the bronchial mucosa and submucosa. Their number was significantly increased compared with those in control tissue. Immunolocalization for ICAM-1, the ligand of Mac-1 and LFA-1, was detected in the endothelial cells of capillaries and venules, in the mononuclear cells in submucosa, and in the basal layer of the epithelium. Endothelial cells in capillaries and venules were also strongly positive for VCAM-1, the ligand of VLA-4. Immunolocalization for E-selectin was detected in some endothelial cells in capillaries and venules in bronchial submucosa, whereas there were very few positive cells in the bronchial tissues from control subjects. In situ hybridization demonstrated ICAM-1 mRNA expression in the endothelial cells and mononuclear cells in bronchial submucosa. Immunoelectron microscopy for ICAM-1, VCAM-1, and E-selectin demonstrated de novo synthesis of these molecules and their expression along the luminal cell membrane of endothelial cells. These results suggested that ICAM-1, VCAM-1, and E-selectin were newly synthesized prior to spontaneous asthma attacks, and that their expression, particularly that of VCAM-1, may play a key role in eosinophil infiltration into the airway.
Am J Respir Cell Mol Biol 1995 Jan
PMID:In situ expression of the cell adhesion molecules in bronchial tissues from asthmatics with air flow limitation: in vivo evidence of VCAM-1/VLA-4 interaction in selective eosinophil infiltration. 752 29

Endothelial adhesion molecules are important in the recruitment of leukocytes to inflammatory sites. Nasal polyps characteristically contain a leukocyte infiltrate in which eosinophils often are remarkably prominent. We have studied whether this feature is related to a particular profile of adhesion molecules on the local microvascular endothelium. Nasal polyps were obtained from 15 patients. Mucosal biopsy specimens of the lower and the middle turbinate from the same patients as well as from three control subjects served as reference tissue. Expression of endothelial adhesion molecules and the relative numbers of eosinophils and neutrophils were examined by two- and three-color immunofluorescence staining. Both the number of eosinophils and the proportion of vessels positive for vascular cell adhesion molecule-1 (VCAM-1) were significantly increased in nasal polyps compared with the turbinate mucosa of the same patients (P = 0.008 and P = 0.001, respectively). By contrast, the number of neutrophils and the relative expression of E-selectin and intercellular adhesion molecule-1 were similar at both tissue sites. Furthermore, the relative number of eosinophils in nasal polyps was well correlated (rs = 0.73, P = 0.006) with the percentage of vessels positive for VCAM-1, but this was not true for neutrophils. Taken together, this direct in situ observation strongly supports the crucial role suggested for VCAM-1 in human eosinophil extravasation at inflammatory sites.
Am J Respir Cell Mol Biol 1995 Jun
PMID:Eosinophil infiltration is related to increased expression of vascular cell adhesion molecule-1 in nasal polyps. 753 73

Several studies have demonstrated that bronchial epithelial cells are capable of synthesizing proinflammatory cytokines that may influence eosinophil and neutrophil activity. We have cultured human bronchial epithelial cells to confluence, as explant cultures, and investigated the effect of conditioned medium from these cells on (1) the chemotaxis of eosinophils and neutrophils and (2) the adherence of these cells to cultured human endothelial cells. Analysis of cytokines, namely interleukin-1 beta (IL-1 beta), interleukin-8 (IL-8), tumor necrosis factor alpha (TNF alpha), granulocyte/macrophage colony-stimulating factor (GM-CSF), and RANTES, which are thought to be involved in these processes, demonstrated that all these cytokines were synthesized and released constitutively from the bronchial epithelial cell cultures. Conditioned medium obtained after 24 h of incubation significantly increased the chemotaxis of eosinophils and neutrophils, from median values of 4.0 cells/per high power field (hpf) (range, 3.0 to 7.0) and 17 cells/hpf (range, 13.0 to 25.0), respectively, for medium 199, to median values of 11.0 cells/hpf (range, 9 to 12; P = 0.005) and 30 cells/hpf (range, 19 to 33; p = 0.01). Whereas anti-GM-CSF and anti-IL-8 neutralizing monoclonal antibodies significantly attenuated the conditioned medium-induced chemotaxis of eosinophils and neutrophils, anti-RANTES neutralizing antibody significantly attenuated the chemotaxis of only eosinophils. Conditioned medium also significantly increased the percentage of eosinophils and neutrophils adhering to endothelial cells in a dose-dependent manner. Both anti-human TNF alpha and anti-human IL-1 beta neutralizing antibodies significantly attenuated the conditioned medium-induced adherence of eosinophils and neutrophils to the endothelial cells and were found to have an additive effect when studied together. Similarly, treatment of endothelial cells with either anti-ICAM-1 or anti-E-selectin, for 1 h before co-culture with eosinophils and neutrophils, significantly attenuated the conditioned medium-induced adherence of both eosinophils and neutrophils to endothelial cells. Treatment of endothelial cells with anti-VCAM-1 attenuated the adherence of eosinophils but not neutrophils. These results suggest that human bronchial epithelial cells, through their ability to generate proinflammatory mediators, are likely to play a role in the pathogenesis of airway disease by influencing chemotaxis and adherence of eosinophils and neutrophils.
Am J Respir Cell Mol Biol 1995 Dec
PMID:The effect of conditioned medium from cultured human bronchial epithelial cells on eosinophil and neutrophil chemotaxis and adherence in vitro. 757 11

For functional studies of the integrin alpha 4 cytoplasmic domain, we have expressed the following in K562 and Chinese hamster ovary (CHO) cells: 1) wild-type alpha 4 (called X4C4), 2) two chimeric forms of alpha 4 (called X4C2 and X4C5) that contain the cytoplasmic domains of alpha 2 and alpha 5, respectively, and 3) alpha 4 with no cytoplasmic domain (X4C0). Cytoplasmic domain exchange had no effect on VLA-4-dependent static cell adhesion or tethering to VCAM-1 in conditions of shear flow. However, the presence of the alpha 2 or alpha 5 tails markedly enhanced VLA-4-dependent K562 cells spreading (X4C2 > X4C5 > X4C4 > X4C0), increased localization of VLA-4 into focal adhesion-like complexes in CHO cells (X4C2 > X4C5 > X4C4), and strengthened CHO and K562 cell resistance to detachment from VCAM-1 in conditions of shear flow (X4C2 > X4C5 > X4C4 > X4C0). Conversely, the alpha 4 tail supported greater VLA-4-dependent haptotactic and chemotactic cell migration. In the absence of any alpha tail (i.e., X4C0), robust focal adhesions were observed, even though cell spreading and adhesion strengthening were minimal. Thus, such focal adhesions may have relatively little functional importance, and should not be compared with focal adhesions formed when alpha tails are present. Together, these results indicate that all three alpha-chain tails exert defined positive effects (compared with no tail at all), but suggest that the alpha 4 cytoplasmic domain may be specialized to engage in weaker cytoskeletal interactions, leading to diminished focal adhesion formation, cell spreading, and adhesion strengthening, while augmenting cell migration and facilitating rolling under shear flow. These properties of the alpha 4 tail are consistent with the role of alpha 4 integrins on highly motile lymphocytes, monocytes, and eosinophils.
Mol Biol Cell 1995 Jun
PMID:Specialized functional properties of the integrin alpha 4 cytoplasmic domain. 757 86

Programmed cell death (PCD) or apoptosis is a naturally occurring cell suicide pathway induced in a variety of cell types. In many cases, PCD is induced by the withdrawal of specific hormones or growth factors that function as survival factors. In this study, we have investigated the potential role of the extracellular matrix (ECM) as a cell survival factor. Our results indicate that in the absence of any ECM interactions, human endothelial cells rapidly undergo PCD, as determined by cell morphology, nuclei fragmentation, DNA degradation, protein cross-linking, and the expression of the PCD-specific gene TRPM-2. PCD was blocked by plating cells on an immobilized integrin beta 1 antibody but not by antibodies to either the class I histocompatibility antigen (HLA) or vascular cell adhesion molecule-1 (VCAM-1), suggesting that integrin-mediated signals were required for maintaining cell viability. Treatment of the cells in suspension with the tyrosine phosphatase inhibitor sodium orthovanadate also blocked PCD. When other cell types were examined, some, but not all, underwent rapid cell death when deprived of adhesion to the ECM. These results suggest that in addition to regulating cell growth and differentiation, the ECM also functions as a survival factor for many cell types.
Mol Biol Cell 1993 Sep
PMID:The extracellular matrix as a cell survival factor. 825 97


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