[Other non-Fukuyama congenital muscular dystrophy].
Explore the source record for details and available documents.
Antigens, CD↗
SEARCH · Search PubMed
Results for “Integrin alpha Chains”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Expression of the myeloid-specific leukocyte integrin gene CD11d during macrophage foam cell differentiation and exposure to lipoproteins.
The leukocyte integrin gene CD11d is expressed predominantely on subsets of the myelomonocytic lineage (myeloid cells), particularly on macrophage foam cells and splenic red pulp macrophages. Its expression pattern clearly differs from myeloid-specific leukocyte integrins CD11b and CD11c and the leukocyte-specific integrin CD11a. Although the functions of CD11d have not been determined in any detail, its expression in these cell types suggests that it may play a role in the atherosclerotic process. To better understand how this gene is regulated, the steady-state level of CD11d mRNA in differentiating bone marrow CD34+CD38- cells, peripheral blood monocytes, and monocytic cell lines was assessed by Northern blot analysis and RT-PCR and compared with those of CD11a, CD11b, and CD11c. Expression of CD11d occurs early in CD34+CD38- cells, rises, and then decreases, in contrast to the expression of the other leukocyte integrins. Expression of CD11d reappears in peripheral blood monocytes differentiating to macrophage foam cells. Oxidized lipoproteins (OxLDL) and acetylated lipoproteins (AcLDL) failed to upregulate CD11d following differentiation of peripheral blood monocytes or the monocytic cell line HL60. However, when both OxLDL and AcLDL were present during differentiation, CD11d was further upregulated. This suggests that expression of CD11d is coordinately regulated with expression of LDL receptors and the development of the foam cell. Site-directed mutagenesis of the -100 to -20 region of the CD11d promoter revealed transcription factor binding sites essential for expression of this gene. Decoy oligonucleotides to the -100 to -20 region taken up by CD34+CD38- cells block their differentiation into myeloid colonies. This suggests that one or more transcription factors that regulate CD11d also are essential for myeloid differentiation, and that the CD11d promoter may be used as a model gene to identify transcription factors essential for myeloid cell differentiation.
CD11 Antigens↗
[Gene expression changes after heat shock by cDNA array analysis].
OBJECTIVE: To study gene expression changes of cells in response to heat stress, we isolated total RNA from Jurkat cells before and after heat shock treatment. METHODS: cDNA was labeled with alpha-32P-dATP during reverse transcription of RNA and then used as probe to cDNA expression array. Autoradiogram images were analyzed by ESTblot software. RESULTS: After heat shock, the expression level of some forty genes increased while that of sixteen genes decreased. In addition to the elevated expression of heat shock genes, expression of c-Jun and CLK-1 increased most remarkably. The genes with notably decreased expression were integrin alpha-4 and transforming growth factor beta. The elevated expression of c-Jun and hsp90 alpha was further confirmed by Northern blot analysis. CONCLUSIONS: The expression of some genes in Jurkat cells changes after heat shock treatment. Heat shock induces elevated expression of hsp, c-Jun, CLK-1 gene while decreases expression of integrin alpha-4 and transforming growth factor beta.
Blotting, Northern↗
Differential expression of homing receptor CD103 on lamina propria lymphocytes and association of CD103 with epithelial adhesion molecules in inflammatory bowel disease.
Intraepithelial lymphocytes play an important role in mucosal immunology, and are involved in the pathogenesis of inflammatory bowel disease. We studied expression of CD103 on mucosal lymphocytes with epithelial adhesion molecules in patients with inflammatory bowel disease. Surgical specimens of human colon were obtained from 12 patients with ulcerative colitis, 12 patients with Crohn's disease, and 5 controls. Frozen sections were cut and expression of CD103 on lymphocytes, E-cadherin, CD44V3, and CD44v6 on intestinal epithelium was studied. Frequency of CD103-positive intraepithelial lymphocytes did not differ among controls, patients with ulcerative colitis, and patients with Crohn's disease. The frequency of CD103-positive lamina propria lymphocytes was significantly higher in patients with Crohn's disease than in controls and patients with ulcerative colitis. The frequency of CD103-positive intraepithelial lymphocytes was significantly correlated with that of lamina propria lymphocytes in patients with ulcerative colitis. The frequency of CD103-positive intraepithelial lymphocytes was significantly correlated with epithelial E-cadherin expression but that of lamina propria lymphocytes was not. Differential up-regulation of CD103 expression on lamina propria lymphocytes in Crohn's disease may indicate differential humoral or cellular regulation in inducing CD103 molecules on lymphocytes in patients with this disease.
Antigens, CD↗
Phorbol esters alter alpha4 and alphad integrin usage during eosinophil adhesion to VCAM-1.
We examined the effect of the protein kinase C activator phorbol-12-myristate-13-acetate (PMA) on the human eosinophil adhesion molecule phenotype and attachment to VCAM-1 via alpha4 and alphad integrins under static and flow conditions. PMA increased surface expression of alphad integrins and decreased alpha4 integrin expression. Under static conditions, eosinophils bound well to VCAM-1, primarily via alpha4beta1 integrins, with a minor alphadbeta2 integrin component. Unexpectedly, PMA-stimulated eosinophils bound equally well to VCAM-1 and albumin in a temperature- and divalent cation-dependent manner, yet adhesion was independent of beta1 and beta2 integrins. Under flow conditions, eosinophils readily attached to VCAM-1, and adhesion was inhibited by both alpha4 and alphad mAbs (95 and 50% inhibition, respectively). Many fewer PMA-stimulated eosinophils bound to VCAM-1 under flow conditions, but both alpha4 and alphad mAbs inhibited adhesion equally. Thus, PMA alters eosinophil integrin expression and the relative contributions of alpha4 and alphad integrins during attachment to VCAM-1.
Carcinogens↗
The effect of extracellular substance components on the proliferation and expression of hormones in cultured cells of medullary thyroid carcinomas.
The effects were examined of selected extracellular medium (ECM) components on the proliferation of medullary thyroid carcinoma cells and on the production of calcitonin and CGRP. Human TT cells and rat rMTC cells were cultured for 24, 48 and 72 hours on glass coated with type I collagen, fibronectin or poly-D-lysine. More pronounced proliferation was demonstrated by TT cells grown on poly-Dlysine or collagen in comparison with the control and less pronounced proliferation was typical of cells grown on fibronectin. On the other hand, rMTC cells were more markedly manifest on any ECM substrates than that on glass. Alterations in the proliferation were paralleled by changes in the expression of CT and CGRP.
Animals↗
Hairy cell leukemia-variant--a case report.
Hairy-cell leukemia-variant (HCL-V) is a rare B-cell disorder which accountsfor 10% of HCL cases. The main features are splenomegaly, lymphocytosis and cytopenias without monocytopenia. The circulating cells have a morphology intermediate between prolymphocytes and hairy cells. The immunophenotype shows a mature B-cell phenotype with expression of B-cell antigens CD11c and CD103 but unlike typical hairy cell the cells are negative for CD25. The histology of bone marrow and spleen shows a pattern of infiltration similar to that in HCL. We present a case of HCL-V in a 66-year-old male. The bone marrow findings, immunophenotypic profile and electron microscopic features are described. The patient underwent splenectomy which also revealed infiltration by leukemia. Patients are resistant to alkylating agents and alpha-interferon (á-IFN). Splenectomy may be beneficial for long-lasting partial responses in some of the patients and is a good palliative treatment.
Aged↗
Great potential of a panel of multiple hMTH1, SPD, ITGA11 and COL11A1 markers for diagnosis of patients with non-small cell lung cancer.
Research on molecular mechanisms underlying the carcinogenesis of non-small cell lung cancer (NSCLC) may provide gene targets in critical pathways valuable for improving the efficacy of therapy and survival of patients with NSCLC. However, the molecular markers highly sensitive for the prognosis and treatment evaluation of NSCLC are not yet available. To explore candidates, we conducted an oligonucleotide microarray study with three pairs of NSCLC and normal lung tissue, and determined 8 differentially expressed genes including the Human MutT homologue (hMTH1), Surfactant protein D (SPD), Human hyaluronan binding protein 2 (HABP2), Crystalline-mu (CRYM), Ceruloplasmin (CP), Integrin alpha-11 subunit (ITGA11), Collagen type XI alpha I (COL11A1), and Lung-specific X protein (Lun X). Four lung cancer-related markers MUC-1, hTERT, hnRNP B1, and CK-19 were also incorporated for further analysis. The expression profiles of the twelve genes in seventy pairs of NSCLC tumor and normal lung tissue were then detected quantitatively by using membrane array and quantitative real-time PCR (qRT-PCR). The data of the membrane array and qRT-PCR were compared for consistency and the potential of these mRNA markers in clinical application. The results showed that membrane array and qRT-PCR obtained consistent data for the tested genes in both sensitivity and specificity (correlation coefficient 0.921, p<0.0001). For patients' clinicopathological characteristics, the overexpression of hMTH1, SPD, HABP 2, ITGA11, COL11A1, and CK-19 was significantly correlated with the pathological stage (p<0.05). In addition, the overexpression of hMTH1, SPD, ITGA11, and COL11A1 was correlated with lymph node metastasis and poor prognosis. This is the first report relating SPD to a prognosis marker for NSCLC. Moreover, the combined detection of these four mRNA markers by membrane array had a sensitivity of 89% and a specificity of 84% for NSCLC, significantly higher than these markers had achieved separately. In conclusion, we identified mRNA markers for NSCLC prognosis and therapy evaluation from differentially expressed genes determined by using micro-array. Further studies are needed to collect the data of the mRNA markers used in clinical practice.
Adult↗
A human monoclonal autoantibody to platelet glycoprotein IIb derived from normal human lymphocytes.
Tonsillar lymphocytes from an otherwise healthy nonthrombocytopenic male child were fused with the lymphoblastoid cell line GM 4672. Twenty of 472 (4%) hybridomas had antiplatelet reactivity detected using intact platelets in an enzyme-linked immunosorbent assay. One hybridoma (STO 171) reacted to platelet glycoprotein IIb (integrin alpha IIb) as determined by radioimmunoprecipitation and immunoblotting. Antibody specificity was confirmed using immunodepletion experiments with isotypic antibodies derived from a mutlitransfused Glanzmann's thrombasthenic patient. The antibody reactivity was restricted to platelets and did not react with other integrin alpha-chain proteins expressed on granulocytes or cultured human brain-derived microvascular endothelial cells. These studies indicate that lymphocytes of normal, nonthrombocytopenic individuals have the genetic potential to produce antiplatelet autoantibodies.
Antibodies, Monoclonal↗
Sickle reticulocytes adhere to VCAM-1.
Adherence of sickle (SS) erythrocytes to endothelial cells represents interactions between red blood cell (RBC) and endothelial cell surface molecules. To enhance our understanding of the ligands involved, we transfected COS cells with the cDNAs of two endothelial cell adhesion molecules, VCAM-1 and E-selectin, and measured the binding of normal and sickle RBCs after static incubation. The percentage of COS cells with rosettes (five or more adherent RBCs) was determined. Normal RBCs did not adhere to VCAM-1-transfected COS cells. Unfractionated SS RBCs formed rosettes on the VCAM-1-transfected COS cells (mean +/- SD, 5.85% +/- 4.98%). Low-density SS RBCs were more adherent than high-density SS RBCs (P < .005). The adherent SS RBCs were a young reticulocyte population, staining positively for transferrin receptor. Another measure of reticulocyte age, RNA content, also correlated with adherence. SS RBC binding was specific--inhibitable by antibodies to either VCAM-1 or the alpha 4 integrin chain of VLA-4. In contrast, there was no significant adherence of normal or SS RBCs to E-selectin-transfected COS cells. These results suggest that young reticulocytes bind to endothelial cell VCAM-1 via VLA-4 integrin.
Anemia, Sickle Cell↗
The Peyer's patch high endothelial receptor for lymphocytes, the mucosal vascular addressin, is induced on a murine endothelial cell line by tumor necrosis factor-alpha and IL-1.
The specificity of lymphocyte homing from the blood into a tissue is determined in part by complementary pairs of adhesion receptors on lymphocytes and endothelial cells termed homing receptors and vascular addressins, respectively. The mucosal vascular addressin involved in lymphocyte homing to Peyer's patches is a 66-kDa glycoprotein, MAdCAM-1. Investigation of the regulation and molecular genetics of MAdCAM-1 have been hampered by the lack of a murine cell line expressing this adhesion molecule. We show herein using indirect immunofluorescence studies that MAdCAM-1 can be induced on a murine endothelial cell line, bEnd.3, by cytokines and LPS. Western blot analysis of MAdCAM-1 purified by affinity column chromatography from TNF-alpha-treated bEnd.3 cells demonstrates a 66-kDa protein that comigrates in SDS-PAGE with the MAdCAM-1 constitutively found on high endothelial venules in murine mesenteric lymph nodes. Comparison of MAdCAM-1 expression on the bEnd.3 cells was made to the expression of adhesion molecules ICAM-1 and VCAM-1. MAdCAM-1 and VCAM-1 are not constitutively expressed on the bEND.3 surface but can be induced in a concentration-dependent manner by LPS, TNF-alpha, and IL-1. ICAM-1 is constitutively expressed on the endothelioma surface and expression is increased by TNF-alpha, IL-1, LPS, and IFN-gamma. Surface expression of MAdCAM-1 peaks 12 to 18 h after exposure to TNF-alpha and remains elevated at 48 h, whereas expression of VCAM-1 peaks at 4 h and inducible ICAM-1 peaks between 4 and 18 h. Interestingly, IFN-gamma has differential effects on expression of these three adhesion receptors. IFN-gamma alone induces VCAM-1 and enhances ICAM-1 expression, but does not induce MAdCAM-1. Furthermore, although, preincubation of bEND.3 cells with IFN-gamma modestly increases the induction of ICAM-1 and VCAM-1 in response to TNF-alpha and IL-1, it dramatically reduces the TNF-alpha, IL-1, and LPS-induced expression of MAdCAM-1. MAdCAM-1 on bEnd.3 cells is functional as the murine T lymphoma TK1, known to bind MAdCAM-1, also binds to TNF-alpha-stimulated endothelioma but not to unstimulated cells. This binding is blocked by the antibodies against MAdCAM-1 and against the alpha 4-chain of its integrin receptor, alpha 4 beta 7, on TK1 cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Alpha 4/180, a novel form of the integrin alpha 4 subunit.
The integrin alpha 4 beta 1 (VLA-4) is a versatile cell-cell and cell-extracellular matrix adhesion receptor. The alpha 4 subunit can be expressed on the cell surface in two forms: an intact form (alpha 4/150) and a cleaved form (alpha 4/80,70). Here we have characterized a third form of alpha 4, called alpha 4/180. Although alpha 4/180 (M(r) 180, nonreduced) is different in size than alpha 4/150 (M(r) 150, nonreduced), these two forms are clearly related, as they (i) shared the same amino-terminal sequence, (ii) were both recognized in Western blots by an anti-alpha 4 COOH-terminal antiserum, (iii) migrated with the same apparent size and charge when reduced, and (iv) were both immunoprecipitated using anti-VLA-4 reagents. In pulse-chase experiments, precursors to both forms appeared simultaneously and matured at the same rate, indicating that one is most likely not the biosynthetic precursor of the other. Although reduction of alpha 4/180 to yield alpha 4/150 suggested the release of a cysteine-linked 30-kDa fragment, seven different biochemical techniques failed to identify such a fragment. Also, alpha 4/180 was converted to alpha 4/150 by incubation at pH 11, by treatment with EDTA at 56 degrees C, or by heating in the presence of elevated SDS levels. Together our findings suggest that alpha 4/180 and alpha 4/150 represent different conformations of the same alpha 4 polypeptide, with the former having anomalous slower migration in SDS-polyacrylamide gel electrophoresis. This unusual biochemical feature of alpha 4 is not shared by other beta 1-associated integrin alpha subunits and suggests that VLA-4 has unique structural properties.
Alternative Splicing↗
Semen samples with teratozoospermia show a lower percentage of spermatozoa with detectable adhesion molecules (AM).
Adhesion molecules (AM) are cell surface proteins which interact with ligands and mediate cell-cell bindings. Possibly, the AM are involved in the spermatozoal adhesion to oocytes. Human spermatozoa showed several adhesion molecules on their surface: the alpha chains of the beta 1-integrins VLA alpha 4 (CDw 49d), VLA alpha 5 (CDw 49e) and VLA alpha 6 (CDw 49f), the beta-chain of beta 2-integrins (CD 18) and the matrix proteins laminin and fibronectin. Semen samples with severe teratozoospermia were characterized by a significantly lower percentage (P < 0.01) of spermatozoa with VLA alpha 4, VLA alpha 5 and laminin. VLA alpha 5 (the alpha-chain of the fibronectin receptor) showed the most significant difference between the "normal" and teratozoospermic semen sample groups. This phenomenon could contribute to the explanation of a lower fertilizing capacity of teratozoospermic semen samples.
Cell Adhesion Molecules↗
Upregulation of the surface expression of two integrins and induction of chemotactic activity in a human leukemic cell line by Oncoimmunin-M.
Previously, it was shown that Oncoimmunin-M (OI-M), a recently identified tumor cell-derived 36 kDa protein, is able both to inhibit the proliferation of the human promyelocytic leukemic cell line HL-60 while maintaining viability in culture and to induce a bimodal distribution of CD11b, the alpha chain of the integrin MAC-1, on the cell surface (Packard, B.Z. and Komoriya, A. (1993) J. Biol. Chem. 268, 6356-6363). Now, data which reveal that exposure of HL-60 cells to this factor also brings about an increase in the mean level of surface expression of CD11c, the alpha chain of another leukocyte integrin (p150,95), but leaves CD11a, the alpha chain of the third leukointegrin (LFA-1), virtually unchanged (< 10%) are presented. Comparison of motility studies of OI-M-treated HL-60 bulk populations with control bulk populations demonstrates coinduction of CD11b and CD11c surface upregulation with chemotactic responsiveness to a gradient of the chemoattractant human C5a. Separation of motile from nonmotile cell subpopulations after exposure to C5a further reveals that individual cells which respond to this chemoattractant express increased levels of both CD11b and CD11c relative to unresponsive cells. These data correlate the upregulation of leukointegrins MAC-1 and p150,95 by a tumor cell-derived protein on a preterminally differentiated myeloid cell with chemotactic responsiveness to human C5a.
Cell Line↗
Regulation of integrin alpha 5 beta 1 affinity during myogenic differentiation.
The antigen recognized by U1 alpha, a monoclonal antibody to the alpha chain of a chicken integrin fibronectin receptor, was identified as alpha 5. It identifies the same polypeptide as antisera raised to a sequence from the alpha 5 cytoplasmic domain. The U1 alpha antibody has the unusual functional property for alpha chain antibodies of enhancing the binding of alpha 5 beta 1 for its ligand fibronectin. U1 alpha was used to examine the function of alpha 5 beta 1 during myogenic differentiation. As myogenic cells differentiated from replicating myoblasts to bipolar myocytes there was a decrease in their adhesion to the substrate caused by inactivation of alpha 5 beta 1, which could be reversed by treatment of the cells with U1 alpha. The U1 alpha induced increased adhesion to fibronectin but did not inhibit the differentiation process as measured by formation of myotubes. However, U1 alpha did interfere with both cell migration and morphogenesis of myotubes. The resulting myotubes were smaller, more branched, and showed less regular alignment of nuclei. The results suggest that the ability of the cell to regulate alpha 5 beta 1 affinity is critical to myogenic morphogenesis.
Animals↗
An alternative processing of integrin alpha(v) subunit in tumor cells by membrane type-1 matrix metalloproteinase.
Membrane type-1 matrix metalloproteinase (MT1-MMP) and alpha(v)beta(3) integrin are both essential to cell invasion. Maturation of integrin pro-alpha(v)chain (pro-alpha(v)) involves its cleavage by proprotein convertases (PC) to form the disulfide-bonded 125-kDa heavy and 25-kDa light alpha chains. Our report presents evidence of an alternative pathway of pro-alpha(v) processing involving MT1-MMP. In breast carcinoma MCF7 cells deficient in MT1-MMP, pro-alpha(v) is processed by a conventional furin-like PC, and the mature alpha(v) integrin subunit is represented by the 125-kDa heavy chain and the 25-kDa light chain commencing from the N-terminal Asp(891). In contrast, in cells co-expressing alpha(v)beta(3) and MT1-MMP, MT1-MMP functions as an integrin convertase. MT1-MMP specifically cleaves pro-alpha(v), generating a 115-kDa heavy chain with the truncated C terminus and a 25-kDa light chain commencing from the N-terminal Leu(892). PC-cleavable alpha(3) and alpha(5) but not the PC-resistant alpha(2) integrin subunit are also susceptible to MT1-MMP cleavage. These novel mechanisms involved in the processing of integrin alpha subunits underscore the significance and complexity of interactions between MT1-MMP and adhesion receptors and suggest that regulation of integrin functionality may be an important role of MT1-MMP in migrating tumor cells.
Amino Acid Sequence↗
Identification of monoclonal antibodies with specificity to alpha- or beta-chains of beta 2-integrins using peripheral blood leucocytes of normal and bovine leucocyte adhesion deficient (BLAD) cattle.
The reactivity of monoclonal antibodies entered in the panels of the Third Workshop on Ruminant Leucocyte Antigens with lymphocytes and monocytes of normal and beta 2-integrin deficient (Bovine Leucocyte Adhesion Deficiency: BLAD) animals was determined by flow cytometry to investigate potential specificities to alpha- or beta-chains of beta 2-integrins. From the 13 monoclonal antibodies that were entered as having specificity for CD11/CD18 antigens, ten were confirmed correct, but three had reactivity with cells from BLAD animals. We conclude that our approach provides an easy way to reliably identify the majority of beta 2-integrin specific monoclonal antibodies.
Animals↗
The LIM-only proteins FHL2 and FHL3 interact with alpha- and beta-subunits of the muscle alpha7beta1 integrin receptor.
FHL1, FHL2, and FHL3 are members of the four and one-half LIM domain protein subclass that are expressed in striated muscles. Here we show that FHL2 and FHL3 are novel alpha(7)beta(1) integrin-interacting proteins. They bind both the alpha- and the beta-subunit as well as different splice isoforms. The minimal binding sites for FHL2 and FHL3 on beta(1A)-chain overlap, whereas on alpha(7A) and alpha(7B) subunits they are situated adjacent. Determining the binding sites for integrins on FHL2 or FHL3 revealed that the suprastructure of the whole molecule is important for these associations, rather than any single LIM domain. Immunofluorescence studies with cells expressing full-length FHL proteins or their deletion mutants showed that FHL2 and FHL3 but not FHL1 colocalize with integrins at cell adhesion sites. Further, their recruitment to the membrane results from binding to either the alpha- or the beta-chain of the integrin receptor. The association of FHL2 or FHL3 with integrin receptors neither influences attachment of cells to different substrates nor changes their migration capacity. However, in cardiac and skeletal muscles, FHL2 and FHL3, respectively, are colocalized with alpha(7)beta(1) integrin receptor at the periphery of Z-discs, suggesting a role in mechanical stabilization of muscle cells.
Actins↗