Search PubMed⌕ Search

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.

At least 145 records · Page 8Linked to original sources
PubMed2006

Bovine chondrocyte behaviour in three-dimensional type I collagen gel in terms of gel contraction, proliferation and gene expression.

This study evaluated the in vitro behaviour of bovine chondrocytes seeded in collagen gels, promising recently reported scaffolds for the treatment of full-thickness cartilage defects. To determine how chondrocytes respond to a collagen gel environment, 2 x 10(6) chondrocytes isolated from fetal, calf and adult bovine cartilage were seeded within type I collagen gels and grown for 12 days in both attached and floating (detached from the culture dish after polymerisation) conditions. Monolayer cultures were performed in parallel. All chondrocytes contracted floating gels to 55% of the initial size, by day 12. Contraction was dependent on initial cell density and inhibited by the presence of dihydrocytochalasin B as previously observed with fibroblasts. Gene expression was determined using conventional and real-time PCR. The chondrocyte phenotype was better maintained in floating gels compared to attached gels and monolayers. This was demonstrated by comparing the ratio of COL2A1/ COL1A2 mRNA and also of alpha10/alpha11 integrin mRNA. A strong up-regulation of MMP13 expression was measured at day 12 in floating gels. The composition of cartilage-like tissue obtained by growing chondrocytes in a collagen gel varied depending on the floating or attached conditions and initial cell density. It is thus important to consider these parameters when using this culture system in order to prepare a well-defined implant for cartilage repair.

Animals↗
PubMed2004

Involvement of beta(1) integrin in betaAP-induced apoptosis in human neuroblastoma cells.

Integrin-mediated cell adhesion is required for cell survival and differentiation. Recently, integrins have been proposed as a target for beta-amyloid peptide (betaAP) neurotoxicity. We report here that treatment with betaAP (1-42) or with the active betaAP fragment (25-35) induced a great deal of apoptosis in SK-N-BE and SH-SY5Y cell lines. In the presence of either collagen I degrees, fibronectin, or laminin, betaAP toxicity was severely reduced. This protective effect seems to be mediated by integrins, because preincubation of neuroblastoma cells with antibodies directed against beta(1) and alpha(1) integrin subunits greatly enhanced betaAP-induced apoptosis. In addition, treatment with betaAP induced a strong reduction of beta(1) and alpha(1) integrin subunits expressed in plasma membrane, which occurred 3 h after treatment, before the appearance of the apoptotic morphology. The rapid downregulation of the alpha(1)beta(1) integrin was almost completely recovered 15-24 h after betaAP treatment and was not prevented by cycloheximide. In conclusion, our data indicate a relationship between betaAP neurotoxicity and modulation of alpha(1)beta(1) integrin expression, and support the hypothesis that aberrant integrin function may play a significant role in betaAP-mediated neurotoxicity.

Alzheimer Disease↗
PubMed2004

Expression of integrin-alphaE by mucosal mast cells in the intestinal epithelium and its absence in nematode-infected mice lacking the transforming growth factor-beta1-activating integrin alphavbeta6.

Peak intestinal mucosal mast cell (MMC) recruitment coincides with expulsion of Trichinella spiralis, at a time when the majority of the MMCs are located within the epithelium in BALB/c mice. Although expression of integrin-alpha(E)beta(7) by MMCs has not been formally demonstrated, it has been proposed as a potential mechanism to account for the predominantly intraepithelial location of MMCs during nematode infection. Co-expression of integrin-alpha(E)beta(7) and the MMC chymase mouse mast cell protease-1, by mouse bone marrow-derived mast cells, is strictly regulated by transforming growth factor (TGF)-beta(1). However, TGF-beta(1) is secreted as part of a latent complex in vivo and subsequent extracellular modification is required to render it biologically active. We now show, for the first time, that intraepithelial MMCs express integrin-alpha(E)beta(7) in Trichinella-infected BALB/c and S129 mice. In S129 mice that lack the gene for the integrin-beta(6) subunit and, as consequence, do not express the epithelial integrin-alpha(v)beta(6), integrin-alpha(E) expression is virtually abolished and recruitment of MMCs into the intestinal epithelium is dramatically reduced despite significant overall augmentation of the MMC population. Because a major function of integrin-alpha(v)beta(6) is to activate latent TGF-beta(1,) these findings strongly support a role for TGF-beta(1) in both the recruitment and differentiation of murine MMCs during nematode infection.

Animals↗
PubMed2003

Immunohistochemical localisation of extracellular matrix proteins in the periodontium during cementogenesis in the rat molar.

OBJECTIVE: The development of the periodontium involves the coordinated expression of numerous extracellular matrix (ECM) macromolecules and their receptors (integrins). The aim of this study was to determine the expression of selected hard and soft tissue matrix molecules and the integrin alpha5beta1 in the periodontal tissues, during cementogenesis in the rat molar. METHODS: Using immunohistochemical methods, the distribution of the extracellular matrix proteins, fibronectin, tenascin, and bone sialoprotein (BSP), as well as the integrin subunits alpha5 and beta1 were studied in rats aged 3, 5 and 8 weeks. RESULTS: Fibronectin was widely distributed in the gingival epithelium, gingival connective tissue and in the periodontal ligament. Tenascin expression was less marked compared with fibronectin, but was more distinctly associated with cells and peri-cellular areas of the epithelial-connective tissue interface, the gingiva and within the periodontal ligament. The fibronectin-receptor alpha5beta1 integrins were expressed by epithelial cells, periodontal ligament cells and gingival fibroblasts. A notable finding was the increased staining intensity of fibronectin, tenascin and alpha5beta1 integrin in all 5-week old molar sections in the periodontal ligament matrix and cells, apical to the cemento-enamel junction (CEJ) along the alveolar crest (AC) ridge height. Bone sialoprotein was distinctly associated with the hard tissues of the periodontium as acellular cementum and alveolar bone matrix expressed bone sialoprotein throughout all sections, in all age groups. CONCLUSIONS: In conclusion, this study has demonstrated the selective distribution of several hard and soft tissue matrix molecules during periodontogenesis. The results highlight the complex nature of interactions of various proteins and molecules during development. The interactions between these molecules and their specific roles in development and regeneration await further investigation.

Animals↗
PubMed2003

Posterior migration of the salivary gland requires an intact visceral mesoderm and integrin function.

The final overall shape of an organ and its position within the developing embryo arise as a consequence of both its intrinsic properties and its interactions with surrounding tissues. Here, we focus on the role of directed cell migration in shaping and positioning the Drosophila salivary gland. We demonstrate that the salivary gland turns and migrates along the visceral mesoderm to become properly oriented with respect to the overall embryo. We show that salivary gland posterior migration requires the activities of genes that position the visceral mesoderm precursors, such as heartless, thickveins, and tinman, but does not require a differentiated visceral mesoderm. We also demonstrate a role for integrin function in salivary gland migration. Although the mutations affecting salivary gland motility and directional migration cause defects in the final positioning of the salivary gland, most do not affect the length or diameter of the salivary gland tube. These findings suggest that salivary tube dimensions may be an intrinsic property of salivary gland cells.

Animals↗
PubMed2003

Role of multiple beta1 integrins in cell adhesion to the disintegrin domains of ADAMs 2 and 3.

ADAM disintegrin domains can support integrin-mediated cell adhesion. However, the profile of which integrins are employed for adhesion to a given disintegrin domain remains unclear. For example, we suggested that the disintegrin domains of mouse sperm ADAMs 2 and 3 can interact with the alpha6beta1 integrin on mouse eggs. Others concluded that these disintegrin domains interact instead with the alpha9beta1 integrin. To address these differing results, we first studied adhesion of mouse F9 embryonal carcinoma cells and human G361 melanoma cells to the disintegrin domains of mouse ADAMs 2 and 3. Both cell lines express alpha6beta1 and alpha9beta1 integrins at their surfaces. Antibodies to the alpha6 integrin subunit inhibited adhesion of both cell lines. An antibody that recognizes human alpha9 integrin inhibited adhesion of G361 cells. VLO5, a snake disintegrin that antagonizes alpha4beta1 and alpha9beta1 integrins, potently inhibited adhesion of both cell lines. We next explored expression of the alpha9 integrin subunit in mouse eggs. In contrast to our ability to detect alpha6beta1, we were unable to convincingly detect alpha9beta1 integrin on the surface of mouse eggs. Moreover, treatment of mouse eggs with 250 nm VLO5, which is 250 fold over its approximately IC(50) for inhibition of somatic cell adhesion, had minimal effect on sperm-egg binding or fusion. We did detect alpha9 integrin protein on epithelial cells of the oviduct. Additional studies showed that antibodies to the alpha6 and alpha7 integrins additively inhibited adhesion of mouse trophoblast stem cells and that an antibody to the alpha4 integrin inhibited adhesion of MOLT-3 cells to these disintegrin domains: Our data suggest that multiple integrins (on the same cell) can participate in adhesion to a given ADAM disintegrin domain and that interactions between ADAMs and integrins may be important for sperm transit through the oviduct.

ADAM Proteins↗
PubMed2002

Collagen-binding I domain integrins--what do they do?

Collagens are the most abundant proteins in the mammalian body and it is well recognized that collagens fulfill an important structural role in the extracellular matrix in a number of tissues. Inactivation of the collagen alpha 1(I) gene in mice results in embryonic lethality and collagen mutations in humans cause defects leading to disease. Integrins constitute a major group of receptors for extracellular matrix components, including collagens. Currently four collagen-binding I domain-containing integrins are known, namely alpha 1 beta 1, alpha 2 beta 1, alpha 10 beta 1 and alpha 11 beta 1. Unlike the undisputed role of collagens as structural elements, the biological importance of integrin mediated cell-collagen interactions is far from clear. This is in part due to the limited information available on the most recent additions of the integrin family, alpha 10 beta 1 and alpha 11 beta 1. Future studies using gene inactivation of individual and multiple integrin genes will allow testing of the hypothesis that collagen-binding integrins have redundant functions but will also shed light on their importance in pathological conditions. In this review we will describe what is currently known about the collagen-binding integrins and discuss their biological functions.

Animals↗
PubMed1999

Skin-associated lymphocytes in the peripheral blood of patients with atopic dermatitis: signs of subset expansion and stimulation.

BACKGROUND: Skin-associated T cells are defined by the cutaneous lymphocyte-associated antigen (CLA). In atopic dermatitis (AD), CLA+ T cells harbor allergen-reactive memory cells, spontaneously secrete TH2 cytokines, and display signs of increased in vivo activation, thus relating the subset to the central disease pathomechanisms. OBJECTIVES: It is not known whether the proportion of circulating CLA+ T cells might be expanded in AD. We were therefore prompted to compare the peripheral blood lymphocyte subpopulations of patients with AD with those of control subjects. METHODS: We used 3-color flow cytometry to investigate age-matched peripheral blood samples of pediatric and young adult patients with mild (n = 21) or severe (n = 15) AD, patients with allergic/atopic diseases not involving the skin (n = 9), and healthy control subjects (n = 14). RESULTS: We found no differences among the study groups with respect to the general proportions of T cells, CD4(+) T cells, CD8(+) T cells, B cells, NK cells, CD103(+) T cells, and CD25(+) T cells among total circulating lymphocytes. However, there were slightly more CD4(+) memory cells and clearly more HLA-DR+ T cells in patients with severe AD. Most remarkably, patients with severe AD had a significantly expanded proportion of CLA+ T cells (P =.024) and CLA+/CD4(+) T cells (P =.006) but similar proportions of CLA+/CD8(+) T cells compared with control subjects. Patients with severe AD also had distinctly more HLA-DR+/CLA+ T cells than control subjects (P =. 005). Similar alterations were seen in patients with mild AD, but these were not statistically significant. After correction for age, all differences were significant only in probands less than 10 years of age. CONCLUSIONS: Circulating skin-associated T cells (CLA+) show signs of subset expansion and enhanced activation in patients with AD. These alterations, compared with control values, affect CD4(+) memory T cells in particular and are prominent only in children less than 10 years of age.

Adolescent↗
PubMed2003

Interaction of integrin receptors with extracellular matrix is involved in trophoblast giant cell migration in bovine placentomes.

Integrins are heterodimeric glycoproteins involved in cell-cell and cell-extracellular matrix adhesion and signal transduction. We evaluated the distribution and the putative role of integrin receptors and extracellular matrix (ECM) proteins during trophoblast giant cell (TGC) migration and fusion with uterine epithelial cells in the cow. Placentomes from 24 cows, covering day 80 to day 270 of gestation, were used for indirect immunohistochemistry against integrin subunits alpha(1), alpha(2), alpha(3), alpha(4), alpha(5), alpha(6), alpha(v), beta(1), beta(3), beta(4)and ECM proteins collagen type I and IV, fibronectin, laminin. The basement membranes of fetal and maternal epithelia and endothelia were immunoreactive for laminin, fibronectin and collagen IV. Collagens I and IV were found in maternal stroma, while fibronectin was present in fetal and maternal stroma. The integrin subunits alpha(2), alpha(6)and beta(1)were observed in basal aspects of fetal and maternal epithelial and endothelial cells. Additionally, the alpha(6)and beta(1)integrin subunits were colocalized with laminin on TGC. The integrin alpha(2)subunit was also found on TGC, but localized with a strong gradient to the basal side. Cells of the maternal connective tissue, including endothelium, expressed alpha(1), alpha(2), alpha(3), alpha(5), alpha(6), alpha(v), beta(3)and beta(4). The expression of alpha(2), alpha(5), alpha(v), beta(3)and beta(4) occurred mainly in the septal tips. Cells of the fetal mesenchyme were positive for integrin subunits alpha(1), alpha(2), alpha(3), alpha(4), alpha(5), alpha(6), and beta(1). Our results indicate that alpha(2)beta(1)collagen and alpha(6)beta(1)laminin receptors anchor epi- and endothelial cells to basement membranes. We suggest that TGC migrate along a matrix of laminin and maintain cell-cell contact with mononuclear trophoblast cells via alpha(2)beta(1)heterodimers. Integrins in maternal stroma and fetal mesenchyme may be involved in the regulation of proliferation and differentiation of maternal septa and fetal villi.

Animals↗
PubMed1998

Adhesion molecule phenotype of T lymphocytes in inflamed CNS.

The phenotype of T cells in the central nervous system (CNS) in two models of chronic inflammation (experimental allergic encephalomyelitis and Corynebacterium parvum-induced inflammation) was compared to that of T cells in gut and chronically inflamed subcutaneous tissue and lung. CNS T cells display a similar phenotype in both inflammatory models, and are phenotypically unique compared to T cells from the other inflamed tissues. T cells from inflamed CNS are mainly CD4+ and are the only population examined that express a typical activated/memory phenotype: CD44high/LFA-1high/ICAM-1high/CD45RBlow. The CNS T cells are alpha4beta7-integrin(negative), but express alpha4-integrin and activated beta1 integrin, suggesting expression of the alpha4beta1-heterodimer in an activated state. In contrast, most T cells in gut express low levels of activated beta1 integrin. The CNS T cells lack expression of alpha6 and alphaE integrin chains and L-selectin. In inflamed CNS and inflamed subcutaneous tissue, approximately 50% of T cells express high affinity ligands for P-selectin while fewer than 10% express high affinity ligands for E-selectin. In summary, our data show that, independent of the inflammatory stimulus, T cells recruited into the inflamed CNS are phenotypically distinct from T cells in other inflamed tissues. This finding leads us to hypothesize the existence of a phenotypically distinct 'CNS-seeking' T lymphocyte population.

Animals↗
PubMed2001

Dentate hilar mossy cells and somatostatin-containing neurons are immunoreactive for the alpha8 integrin subunit: characterization in normal and kainic acid-treated rats.

Integrins are heterodimeric cell surface receptors composed of different alpha and beta subunits that mediate cell-cell and cell-extracellular matrix interactions. They have been implicated in the regulation of neuronal migration, differentiation, process outgrowth, and plasticity. The alpha8 integrin subunit associates exclusively with the beta1 subunit to form a receptor (alpha8beta1) for fibronectin, vitronectin, tenascin, and osteopontin. In a previous study, we demonstrated that hippocampal dentate hilar neurons are immunoreactive for alpha8. The present study identifies the major types of alpha8-immunoreactive hilar neurons and characterizes the effects of kainic acid-induced seizures on alpha8-immunoreactivity in these cells. Examination of the hilus in normal rats revealed alpha8-immunoreactivity in the somatodendritic compartments of large hilar neurons identified as mossy cells, including a subset of dendritic thorny excrescences that were contacted by large mossy fiber terminals. alpha8-immunoreactivity also was found in approximately 71% of somatostatin-containing hilar cells. Kainic acid-induced seizures dramatically and rapidly altered the levels and distribution of alpha8-immunoreactivity in hilar neurons. After 1.5 h of seizures, alpha8-immunoreactivity in their dendrites was reduced greatly. One day after kainic acid treatment, labeling was diminished throughout the somatodendritic compartments of most hilar cells. This decrease appeared to be transient, since alpha8 labeling returned to normal levels in surviving hilar neurons within 2 weeks of treatment. In addition, many alpha8-immunoreactive hilar neurons, particularly in caudal dentate regions, were lost 3-5 weeks after kainic acid treatment. Our findings suggest that alpha8beta1 may mediate adhesive interactions of the dendritic processes of mossy cells and somatostatin-containing hilar neurons with other cellular elements or with extracellular matrix components. They also suggest that alpha8 may be susceptible to activity-dependent proteolysis that could modulate its function in the somatodendritic compartment of these cells.

Animals↗
PubMed2000

Cell-cell adhesion via the ECM: integrin genetics in fly and worm.

Integrins are essential for the development of the two genetically tractable invertebrate model organisms, the nematode worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Just two integrins are present in C. elegans: one putative RGD binding integrin alphapat-2betapat-3, corresponding to Drosophila alphaPS2betaPS and vertebrate alpha5beta1, alphaVbeta1 and alpha8beta1, and one putative laminin binding integrin alphaina-1betapat-3, corresponding to Drosophila alphaPS1betaPS and vertebrate alpha3beta1, alpha6beta1 and alpha7beta1. In this review, the function of this minimal set of integrins during the development of these two invertebrates is compared. Despite the differences in bodyplan and developmental strategy, integrin adhesion to the extracellular matrix is required for similar processes: the formation of the link that translates muscle contraction into movement of the exoskeleton, cell migration, and morphogenetic interactions between epithelia. Other integrin functions, such as regulation of gene expression, have not yet been experimentally demonstrated in both organisms. Additional proteins have been characterised in each organism that are essential for integrin function, including extracellular matrix ligands and intracellular interacting proteins, but so far different proteins have been found in the two organisms. This in part represents the fact that the characterisation of the full set of interacting proteins is not complete in either system. However, in other cases different proteins appear to be used for similar functions in the two animals. The continued use of genetic approaches to identify proteins required for integrin function in these two model organisms should lead to the identification of the minimal set of conserved components that form integrin adhesive structures.

Animals↗
PubMed1998

Utilization of a soluble integrin-alkaline phosphatase chimera to characterize integrin alpha 8 beta 1 receptor interactions with tenascin: murine alpha 8 beta 1 binds to the RGD site in tenascin-C fragments, but not to native tenascin-C.

The integrin alpha 8 beta 1 has been reported to bind to fibronectin, vitronectin, and tenascin-C in cell adhesion or neurite outgrowth assays. Here, we describe cDNA cloning of the murine alpha 8 subunit, purification of a recombinant soluble heterodimer consisting of the extracellular domains of the murine alpha 8 and beta1 subunits, and development of a sensitive binding assay using a modified form of this heterodimer fused to alkaline phosphatase (AP). In binding assays, the purified alpha 8 beta 1-AP chimera exhibited the same divalent ion requirements for activation and binding specificity as cell surface alpha 8 beta 1: in the presence of Mn2+ it bound to fibronectin and vitronectin in an RGDS-peptide inhibitable manner. Contrary to previous reports, we found no evidence that alpha 8 beta 1, expressed on K562 cells or as an AP chimera, interacts strongly with native tenascin-C. In binding, adhesion, and spreading assays, significant interactions were observed only to short fragments of tenascin-C containing the third fibronectin type III repeat which contains an RGD sequence. Full length tenascin-C and longer fragments containing this repeat did not appear to serve as ligands, implying that the RGD site in native tenascin-C is a cryptic binding site for this integrin, exposed by removal of adjacent domains. Soluble integrin-AP chimeras should be generally useful for identifying and characterizing integrin interactions with ligands.

Alkaline Phosphatase↗
PubMed2000

Immunohistochemical and molecular characterization of cultured keratinocytes after dispase-mediated detachment from the growth substratum.

Keratinocyte activation comprises changes in protein and gene expression pattern resulting in phenotypic and functional changes necessary for re-epithelialization such as the expression of urokinase-type plasminogen activator (uPA) and its cell surface receptor (uPA-R; CD87). As uPA and uPA-R are rapidly induced after dispase-mediated detachment of cultured normal human epidermal keratinocytes (NHEK) we hypothesized that dispase-mediated detachment may cause a similar "activation" of keratinocytes with uPA and uPA-R being only one aspect of a complex "activation reaction". To test this hypothesis we have comparatively analysed adherent versus detached keratinocyte sheets for selected indicators of keratinocyte activation by immunohistochemistry. Furthermore we have identified genes via subtraction cloning which are up-regulated upon dispase-induced detachment. The analyses provided evidence for an increased transcriptional and translational activity in detached keratinocytes, as indicated by over-expression of several ribosomal components (L3 and S10 ribosomal protein) and transcription factors (initiation factor 4A, elongation factor 1alpha). Increased proliferative activity was indicated by increased expression of the proliferation markers Ki67, keratin 6 and keratin 17. Finally, several markers of keratinocyte activation such as the integrin chain alpha(v), psoriasin, glutathion-S-transferase and heparin-binding epidermal growth factor-like growth factor were up-regulated. Furthermore mevalonate kinase, a molecule as yet unknown to be expressed in keratinocytes, was identified. The findings provide evidence that dispase-mediated detachment in cultured keratinocytes induces a reaction, which comprises the up-regulation of a complex array of proliferation- and migration-related molecules. The pattern of which resembles the activation reaction observed in the re-epithelializing keratinocytes in vivo.

Biomarkers↗
PubMed2003

Salivary gland tumours: immunoexpression of integrins beta 1, beta 3 and beta 4.

BACKGROUND: Integrins, heterodimeric transmembranic adhesion molecules composed of alpha and beta subunits, have been implicated in normal and neoplastic biological processes. We investigated the patterns of expression of integrins subunits beta 1, beta 3 and beta 4 in neoplasms derived from the terminal segment of salivary glands in order to understand their expression patterns in the different structures of these tumours. METHODS: Immunohistochemistry using 'catalized signal amplification' (CSA) detection system was applied to paraffin-embedded specimens of polymorphous low-grade adenocarcinoma, adenoid cystic carcinoma and acinic cell carcinoma. Normal salivary glands were used as controls. RESULTS: Immunoexpression of integrins showed that neoplastic structures of the tumours studied tend to mimic the patterns seen in the normal structures of salivary glands from which they are derived. Anaplastic cells were negative for all integrins. CONCLUSIONS: This study revealed detailed topography of integrins in malignant tumours derived from intercalated acinar segment of salivary gland and this might be useful in the diagnosis of these lesions, especially of fine-needle aspiration (FNA) products or small specimens derived form incisional biopsies.

Adenocarcinoma↗