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Results for “Integrin beta1”

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At least 1,729 records · Page 96Linked to original sources
PubMed1993

Beta 1 integrin-mediated T cell adhesion is regulated by calcium ionophores and endoplasmic reticulum Ca(2+)-ATPase inhibitors.

Treatment of T lymphoblasts with stimuli that mobilize [Ca2+]i, such as ionophores (ionomycin and A23187) and endoplasmic reticulum Ca(2+)-ATPase inhibitors (thapsigargin, 2,5-di-(tert.-butyl)-hydroquinone and cyclopiazonic acid), activated T cell binding to extracellular matrix (ECM) proteins. T lymphoblast adhesion to ECM proteins stimulated by ionomycin, thapsigargin, or PMA was inhibited by an anti-beta 1 integrin mAb (4B4), confirming the role of beta 1 integrins in regulated T cell-ECM interactions. Study of the alpha integrin subunit specificity of activated lymphoblast-fibronectin interactions demonstrated that alpha 5 beta 1 was the major integrin receptor regulating binding to fibronectin. These results indicate that intracellular Ca2+ mobilization plays a major contributory role in the activation of T cell beta 1 integrins.

Antibodies, Monoclonal↗
PubMed1995

Jararhagin and jaracetin: novel snake venom inhibitors of the integrin collagen receptor, alpha 2 beta 1.

Two novel proteins, jararhagin and jaracetin, were purified from Bothrops jararaca viper venom. Jararhagin is a 55-kDa member of the metalloprotease-disintegrin family. Jaracetin is a 60-kDa dimer representing a differently processed form of jararhagin. Like botrocetin, a previously described viper venom protein, jararhagin and jaracetin modulated binding of von Willebrand Factor to the glycoprotein Ib-IX complex on platelets through a specific interaction with the von Willebrand Factor A1 domain. Both jararhagin and jaracetin, but not botrocetin, also blocked alpha 2 beta 1-dependent platelet adhesion to collagen, a receptor interaction mediated through a homologous A domain on the integrin alpha 2 subunit.

Animals↗
PubMed1995

Integrin-linked tyrosine phosphorylation increases membrane association of protein kinase C alpha in pancreatic acinar cells.

Ligation of beta 1 integrin receptors resulted in increased tyrosine phosphorylation of at least five proteins (Mrest = 110, 85, 55, 30 and 24 kD) from rat pancreatic acinar cells. Increased protein kinase C (PKC) activity and elevated amounts of immunoreactive PKC alpha were demonstrated in membrane fractions from integrin-ligated acinar cells. Membrane translocation of PKC alpha was confirmed using scanning confocal laser microscopy in immunocytochemical preparations of acinar cells following beta 1 integrin ligation. These studies establish the presence of a beta 1 integrin-linked protein tyrosine phosphorylation system in exocrine pancreatic cells and provide evidence for integrative activity of this system with PKC, a primary signalling pathway of central importance in these cells.

Animals↗
PubMed1995

Novel isoform of beta 1 integrin expressed in skeletal and cardiac muscle.

We describe a novel isoform of the beta 1 integrin subunit called beta 1D, which contains a unique cytoplasmic domain, and is expressed specifically in skeletal and cardiac muscle. The beta 1D isoform arises from splicing into the final transcript of an additional exon located between exons 6 and 7. The nucleotide sequence of beta 1D predicts a cytoplasmic domain of 50 amino acids in which the last 21 amino acids of the beta 1A integrin isoform are replaced by a related sequence of 24 amino acids. A beta 1D-specific anti-peptide polyclonal antibody was prepared and immunoprecipitation of tissue extracts with subsequent immunoblotting showed expression of beta 1D isoform only in striated muscle cells.

Adult↗
PubMed1997

A synthetic peptide, FN-C/H-V, from the C-terminal heparin-binding domain of fibronectin promotes adhesion of PMA stimulated U937 cells.

Hematopoietic cells differentially bind to the C-terminal heparin-binding domain of fibronectin depending on the activation state of integrin alpha 4 beta 1. In this study, we have identified a synthetic peptide derived from the C-terminal heparin-binding domain of fibronectin that promotes adhesion of PMA-treated U937 cells (a monocytic cell line) in a dose-dependent manner. A peptide (FN-C/H-V; residues Gln1892 to Gly1910) was active to inhibit adhesion of PMA-treated U937 cells to the 29-kDa fragment comprising the C-terminal heparin-binding domain of fibronectin. A peptide with scrambled version of FN-C/H-V lost the inhibitory activity on the adhesion. Furthermore, the IgG-conjugated FN-C/H-V promoted the adhesion of PMA-treated U937 cells to an extent comparable to that of the 29-kDa fragment. The adhesion of PMA-treated U937 cells on IgG-conjugated FN-C/H-V was inhibited both by anti-alpha 4 beta 1 antibody and by glycosaminoglycans including chondroitin sulfate and heparan sulfate. The other peptide, FN-C/H-II, was also a weak adhesion-promoting domain. These results suggest that the amino acid sequence defined by peptide FN-C/H-V contributes to the main adhesion-promoting activity of the 29-kDa fragment of fibronectin to stimulated U937 cells. The regulation of interactions of alpha 4 beta 1 integrin and glycosaminoglycans with ligands in fibronectin may have important implications for the migration and function of U937 cells.

Amino Acid Sequence↗
PubMed1998

Propensity for macrophage apoptosis is related to the pattern of expression and function of integrin extracellular matrix receptors.

Ligation of integrins to an extracellular matrix activates signal transduction systems which produce multiple responses in different cell types. Adhesion often provides a survival signal to cells; disruption of adhesion frequently results in apoptosis. Our laboratory has utilized apoptosis-sensitive and -resistant cell lines to investigate the role of integrin expression and function in regulation of apoptosis in macrophages. Chronic exposure of murine macrophage-like RAW264.7 cells to apoptosis-inducing agents (bacterial lipopolysaccharide and interferon-gamma) resulted in the generation of a derivative cell line (RES) resistant to apoptosis. Observation of RAW and RES cultures indicated a difference in adhesion between the two cell types. The two cell lines also exhibit significant differences in expression of integrins previously characterized to be important in apoptosis.

Animals↗
PubMed1999

Integrins mediate the inhibitory effect of focal adhesion on angiotensin II-induced p44/42 mitogen-activated protein (MAP) kinase activity in human mesangial cells.

Previously, we reported that the formation of focal adhesion accelerated by accumulation of extracellular matrices may inhibit the angiotensin II-stimulated proliferation of human mesangial cells (HMCs). The process is regulated by p44/42 MAP kinase activity through the mediation of paxillin and GTPase activating proteins. In this report, we investigated the effect of integrin molecules on the angiotensin II-induced p44/42 MAP kinase activation in non-adherent HMCs. The results demonstrated that incubation of cells with both antibody to integrin beta(1) chain (K20) and GRGDS peptide induced integrin clustering, paxillin aggregation, and marked suppression of angiotensin II-induced p44/42 MAP kinase activation. On the other hand, incubation of cells with K20 alone induced integrin clustering without paxillin aggregation and the suppressive effect on angiotensin II-stimulated p44/42 MAP kinase activity. Our results strongly suggest the pivotal role of integrins in the inhibitory effect of focal adhesion on p44/42 MAP kinase activity, the checking system against angiotensin II-induced MAP kinase overactivation.

Angiotensin II↗
PubMed1999

Preparation of monoclonal antibodies to murine platelet glycoprotein IIb/IIIa (alphaIIbbeta3) and other proteins from hamster-mouse interspecies hybridomas.

To obtain mouse-specific monoclonal antibodies (mAbs) against platelet proteins, an Armenian hamster was immunized with washed mouse platelets. Immune splenocytes were then fused with a nonsecreting murine myeloma cell line, and the resulting heterohybridomas were screened for antibody production utilizing an ELISA in which the target antigen was mouse platelets adsorbed onto microtiter plates in the presence of thrombin. Secondary screening assays included ELISA tests using murine fibrinogen or platelets from beta3-integrin knockout mice, flow cytometry, immunoblotting, immunoprecipitation, and a functional assay to identify antibodies that inhibit platelet-fibrinogen interactions. Hybridoma cells producing hamster mAbs against murine glycoprotein (GP) IIb/IIIa, fibrinogen, CD9, and other platelet integrins were identified. Two hybridomas (1B5 and 9C2) producing antibodies that react with the GPIIb/IIIa complex in immunoprecipitation analysis were subcloned twice. Functional analyses by means of aggregation and adhesion assays revealed that 1B5 completely inhibits platelet-fibrinogen interactions, whereas 9C2 does not affect platelet aggregation or platelet adhesion.

Animals↗
PubMed2000

Blockade of JAK2 by tyrphostin AG-490 inhibits antigen-induced eosinophil recruitment into the mouse airways.

We studied the effect of tyrphostin AG-490, a specific Janus kinase 2 (JAK2) inhibitor, on antigen-induced eosinophil recruitment into the airways of sensitized mice and on IL-5-induced chemokinesis and adhesiveness of eosinophils. The in vivo administration of AG-490 prevented antigen-induced eosinophil infiltration in the airways of sensitized mice in a dose-dependent manner. However, the administration of AG-490 did not affect antigen-induced IL-5 production in the airways nor in vitro antigen-induced IL-5 production and T cell proliferation of spleen cells. Furthermore, AG-490 inhibited IL-5-induced chemokinesis and beta1-integrin adhesiveness of eosinophils in vitro. Because antigen-induced eosinophil recruitment into the airways is mediated by IL-5, these results indicate that JAK2 activation is critical for antigen-induced, IL-5-dependent mobilization of eosinophils into the tissue.

Animals↗
PubMed2001

alpha(6) Integrin is the main receptor of human papillomavirus type 16 VLP.

The present study was performed to determine the specific receptor of type HPV-16 using recombinant human papillomavirus-like particle (HPV-16 L1-VLP). The expression levels of alpha(6), beta(1), and beta(4) integrins were determined and compared with the amount of HPV-VLP binding in ten cell lines by flow cytometry. Our results show that the amount of VLP binding and the expression level of alpha(6) integrin are correlated, which was confirmed by an inhibition experiment using antibodies and by immunocytochemistry. Both the expression level of alpha(6) integrin and the amount of HPV-VLP binding were high in cervical cancer cell lines, as the type HPV-16 is the main cause of cervical cancer. The degree of binding of HPV-VLP matched the alpha(6) integrin expression level in cell lines but was not correlated with beta(1) and beta(4) levels, which suggests that alpha(6) integrin is the main receptor of HPV type 16.

Animals↗
PubMed2001

Low asialoglycoprotein receptor expression as markers for highly proliferative potential hepatocytes.

Development of a reliable method to isolate highly proliferative potential hepatocytes will provide insight into the molecular mechanisms of liver regeneration, as well as proving crucial for the development of a biohybrid artificial liver. The aim of this study is to isolate highly proliferative, e.g., progenitor-like, hepatocytes. To this end, we fractionated hepatocytes expressing low and high levels of the asialoglycoprotein receptor (ASGP-R) based on the difference in their adhesion to poly[N-p-vinylbenzyl-O-beta-d-galactopyranosyl-(1-->4)-d-gluconamide] (PVLA), and examined the proliferative activity and gene expression of these fractionated hepatocytes. The results showed that approximately 0.5 to 1% of the total number of hepatocytes, which showed low adhesion to PVLA, expressed low levels of the ASGP-R, while the rest of hepatocyte population with high adhesion to PVLA expressed high levels of the ASGP-R. Interestingly hepatocytes with low ASGP-R expression levels had much higher DNA synthesizing activity (i.e., are much more proliferative) than those with high ASGP-R expression levels. Moreover, hepatocytes with low ASGP-R expression levels expressed higher levels of epidermal growth factor receptor (EGF-R), CD29 (beta1 integrin) and CD49f (alpha6 integrin) and lower levels of glutamine synthetase than those with high ASGP-R expression. These findings suggested that hepatocytes with low adhesion to PVLA due to their low ASGP-R expression could be potential candidates for progenitor-like hepatocytes due to their high proliferative capacity; hence, the low expression of the ASGP-R could be a unique marker for progenitor hepatocytes. The isolation of hepatocytes with different functional phenotypes using PVLA may provide a new research tool for a better understanding of the biology of hepatocytes and the mechanisms regulating their proliferation and differentiation in health and disease.

Animals↗
PubMed1994

VLA-2 mediates the interaction of collagen with endothelium during in vitro vascular tube formation.

A confluent endothelial monolayer can be induced to form vascular tubes in response to collagen. We investigated possible mechanisms of collagen-induced tube formation by using antibodies to the VLA-2 integrin receptor and protein kinase C inhibitors. Pre-incubation of cells with anti-VLA-2 (which recognises both the alpha 2 and beta 1 chains) and AK7 (which recognises only the alpha 2 chain) showed a dose-dependent inhibition of tube formation. At 50 micrograms/ml, anti-VLA-2 completely inhibited collagen-induced tube formation, whereas AK7 caused only partial inhibition. Both chlorpromazine and trifluoperazine, at concentrations of 10 microM, prevented tube formation (> 40% inhibition). In summary, the VLA-2 integrin receptor plays a role in the induction of tube formation by type I collagen. Protein kinase C may be activated during this process.

Amino Acid Sequence↗
PubMed1999

Migratory phenotypes of HSC-3 squamous carcinoma cell line induced by EGF and PMA: relevance to migration of loosening of adhesion and vinculin-associated focal contacts with prominent filopodia.

Cell migration is involved in carcinoma cell invasion and wound healing. We examined motogenic cytokines that potentiated migration of human HSC-3 carcinoma cells. To assess migratory activity, modified Boyden chambers were used. Among a variety of potential motogenic cytokines, epidermal growth factor (EGF) enhanced migration of HSC-3 cells both on collagen and fibronectin. Phorbol myristate acetate (PMA) also enhanced migration. Inhibitors of protein kinase C completely inhibited PMA-induced migration, but only partly inhibited EGF-induced migration. Protein kinase A was also involved in the EGF-induced signaling pathway for migration. Although the signaling pathways were independent, and the cell shape on collagen was different from that on fibronectin, migratory cells stimulated by EGF or PMA showed common morphology on different ligands. The cells were polygonal or round in shape and the loss of long cytoplasmic extensions was noted. Migratory HSC-3 cells stimulated by EGF or PMA became less adhesive to collagen and fibronectin. Since both EGF- and PMA-stimulated migration did not require de novo protein synthesis, the signaling pathways possibly lead to assembly and disassembly of an actin cytoskeleton. Immunofluorescence for vinculin was concentrated into focal contacts in EGF- and PMA-stimulated HSC-3 cells, whereas the fluorescence signal was hardly detected in non-stimulated cells. Talin and beta1 integrin were immunolocalized at focal contacts in non-stimulated cells, and it remained unchanged in stimulated cells. Numerous filopodia visualized with actin immunofluorescence were formed around stimulated HSC-3 cells, whereas filopodia were short and sparse around elongated cytoplasms in non-stimulated cells. Thus, shortening of cytoplasmic extensions with numerous filopodia, loosening of adhesion, and vinculin-associated focal contacts were regarded as migratory phenotypes.

Carcinogens↗
PubMed1993

Lymphocyte-synovial cell interactions: a role for beta 1 and beta 3 integrin-mediated adhesion to cellular fibronectin.

The interactions of lymphocytes with cultured synovial cells derived from rheumatoid arthritis patients were examined. A number of lymphoid cell lines bound to these cells. The adherence of several of these lines was inhibited by antibodies to fibronectin. The adherence of the T cell leukemia Jurkat was sensitive to inhibition by antibodies to the fibronectin receptors alpha 4 beta 1 and alpha 5 beta 1. The adherence of the beta 1 integrin negative B cell line RPMI 8866 was inhibited by antibodies to the vitronectin receptor, alpha v beta 3. The interactions of several other cell lines with synovial cells appeared to be independent of this fibronectin-dependent pathway. These results indicate that multiple potential adhesion pathways for cellular interactions in the tissues may exist. The adherence to cell-associated fibronectin may play a contributory role in such processes for certain lymphocyte subsets.

Cell Adhesion↗
PubMed1994

Control of lymphocyte integrin function: evidence for multiple contributing factors.

The control of lymphocyte adhesion is critical for proper cellular functions. The alpha 2 beta 1 integrin complex serves as a receptor for collagen on lymphocytes. The T cell leukemia Jurkat expresses alpha 2 beta 1 in a latent form on the cell surface. Three types of stimuli, antibody to the alpha 2 chain (JBS2), antibody to the beta 1 chain (JB1B), and phorbol ester (PMA), each induce activation of alpha 2 beta 1-dependent Jurkat binding to collagen. A comparison of the JBS2, JB1B, and PMA induction requirements indicated that the JB1B and the JBS2 effects are not sensitive to staurosporine while the PMA response is completely inhibited. Combinations of functionally saturating concentrations of the stimuli displayed an additive effect. Collectively these results suggest that several factors contribute to the generation of full integrin functionality and cellular adhesion, thus providing a possible basis for incrementally controlling the adhesive potential of lymphoid cells.

Alkaloids↗
PubMed1994

Role of LFA-1, CD2, VLA-5/CD29, and CD43 surface receptors in CD4+ T cell adhesion to B cells.

We investigated the adhesion to B cells of CD4+ T cells both in the resting state and following activation by CD3 cross-linking or stimulation by PMA/ionomycine/IL2 for 6 days. Both resting and activated CD4+ T cell adhesion were inhibited by anti-LFA-1, -CD2, -VLA-5/CD29, and -CD43 antibodies, suggesting coordinated upregulation of T cell adhesion. The CD2 and LFA-1 adhesion pathways were found to act independently, as CD2 was functional in T cells not expressing LFA-1, and vice versa, and as specific antibodies had additive effects. In contrast, LFA-1- and VLA-5/CD29-specific antibodies did not have an additive blocking effect on CD4+ T cell adhesion, suggesting that efficient adhesion requires a competitive association of integrins with cytoskeleton elements. Although the involvement of fibronectin (coated to B cells via VLA-4) in VLA-5-mediated T cell adhesion to B cells is feasible, an anti-fibronectin and a VLA-4-specific antibody had no blocking effect. The involvement of an unidentified B cell ligand can also be envisaged.

Amino Acid Sequence↗
PubMed1995

Migration of human polymorphonuclear leukocytes through a synovial fibroblast barrier is mediated by both beta 2 (CD11/CD18) integrins and the beta 1 (CD29) integrins VLA-5 and VLA-6.

Polymorphonuclear leukocytes (PMNL) accumulate in joint fluid in inflammatory arthritides. We investigated the molecular mechanisms required for PMNL migration through a barrier of human synovial fibroblasts (HSF) grown on microporous filters, as a model of PMNL migration through synovial connective tissue and compared this process with PMNL migration through human dermal fibroblast (HDF) barriers and through human umbilical vein endothelium (HUVE). A small amount of PMNL migration occurred spontaneously only through the synovial fibroblast/filter unit (6-10%). Migration markedly increased through all cell monolayers when the chemotactic factors C5a, IL-8, or zymosan-activated plasma (containing C5adesArg) were added to form a chemotactic gradient. The migration induced by C5a, IL-8, or C5adesArg across HSF was partially inhibited (25-76% depending on stimulus) by mAb to CD18 (beta 2 integrin). The CD18-independent migration induced by IL-8 or C5adesArg was almost completely inhibited by mAbs to beta 1 integrin, but with C5a, inhibition by mAb to beta 1 integrin was only partial (40-50%). Inhibition by mAb to beta 1 integrin required treatment of the PMNL, but not the HSF and was only observed when the function of CD11/CD18 on PMNL was also blocked by a mAb. Treatment of PMNL with mAb to alpha 5 (VLA-5) plus alpha 6 (VLA-6) in combination, was required to inhibit CD18-independent migration through HSF to the degree observed with mAb to beta 1 integrin. There was no qualitative difference in the mechanisms utilized by PMNL for migration through HSF or HDF in response to chemotactic factors. In contrast, PMNL migration across HUVE was almost completely CD18-dependent (85%) with no role for beta 1 integrins. The results suggest that (a) PMNL migration through HSF in response to chemotactic factors utilizes both CD11/CD18 and beta 1 (CD29) integrins; (b) the VLA-5 and VLA-6 members of beta 1 integrins are involved in mediating migration; and (c) PMNL utilize similar mechanisms for migration through HSF and HDF, which are distinct from migration through HUVE.

Antibodies, Monoclonal↗
PubMed1996

VLA-5 in the plasma cell line, FR4ds, acts as a common regulator of VLA-4 and VLA-6 in spreading induced by fibronectin and laminin.

VLA-5 recognizes the GRGDSP sequence of fibronectin (FN) in the extracellular matrix (ECM). We examined the role of beta1 integrin in the spreading of the human plasma cell line, FR4ds, induced by FN and laminin (LN). We first examined the role of VLA-5 in the spreading induced by FN. Anti-alpha4 antibody induced 46.4% inhibition, whereas anti-alpha5 had no effect. A combination of anti-alpha4 and anti-alpha5 enhanced the inhibition of spreading significantly. Complementary inhibition was also demonstrated using the GRGDSP peptide plus anti-alpha4 and the GRGDNP peptide of LN plus anti-alpha4. The results suggested that VLA-5 is a regulator of VLA-4 and that it is involved in the recognition of GRGDNP. We then examined the role of VLA-5 in the spreading induced by LN. Anti-alpha6 induced 53.1% inhibition. Anti-alpha5 alone had no effect. A combination of alpha5 and anti-alpha6, however, significantly enhanced the inhibition of spreading. The combination of GRGDSP plus anti-alpha6 and GRGDNP plus anti-alpha6 resulted in complete inhibition. These results suggested that VLA-5 participates in the recognition of LN cooperatively with VLA-6 and that VLA-5 is a common regulator of VLA-4 and the LN receptor, VLA-6.

Cell Movement↗