Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Integrin beta 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 127 records · Page 7Linked to original sources
PubMed1996

Applications of the MTT assay to functional studies of mouse intestinal intraepithelial lymphocytes.

The MTT [3(4,5-dimethyl-thiazoyl-2-yl)2,5 diphenyl-tetrazolium bromide] and other related colorimetric assays were compared, and applied to functional studies of mouse intestinal intraepithelial lymphocytes and their hybridomas. Functional studies of intestinal lymphocytes included cell adhesion, cytotoxicity, growth inhibition, and proliferation. Our data demonstrate that MTT and related assays are time, labor, and cost saving alternatives to standard radiolabeling assays. The novel application of the MTT method to measure cell-to-cell adhesion and cell-mediated cytotoxicity greatly speed and simplify the determination. The new application of the MTT methods provides a reliable, reproducible, and rapid alternative for the study of intestinal immune cell functions.

Animals↗
PubMed1998

L-selectin and beta7 integrin synergistically mediate lymphocyte migration to mesenteric lymph nodes.

Mesenteric lymph nodes (MLN) drain the gut where nutritive antigens and pathogens are encountered by lymphocytes of the gut-associated lymphoid tissue. We sought to determine how lymphocytes enter the MLN by studying mice double deficient for beta7 integrins and L-selectin. beta7/L-selectin double-deficient lymphocytes did not migrate into MLN. Most importantly, MLN formation was drastically impaired in beta7/L-selectin double-deficient mice. Lymphocyte numbers in MLN from beta7/L-selectin double-deficient mice were tenfold reduced compared to control mice. A high percentage of the few lymphocytes still detected in MLN from beta7/L-selectin double-deficient mice were CD44hi CD18hi, suggesting alternate migration pathways independent of L-selectin and beta7 integrin for these cells. We conclude that the combination of both molecules, L-selectin and beta7 integrin, is indispensable for MLN formation and that these molecules may mediate lymphocyte migration to MLN in a sequential and synergistical manner.

Animals↗
PubMed2000

Human intestinal lamina propria and intraepithelial lymphocytes express receptors specific for chemokines induced by inflammation.

To determine which chemokine receptors might be involved in T lymphocyte localization to the intestinal mucosa, we examined receptor expression on human intestinal lamina propria lymphocytes (LPL), intraepithelial lymphocytes (IEL) and CD45RO+beta7hi gut homing peripheral blood lymphocytes (PBL). Virtually all LPL and IEL expressed CXCR3 and CCR5, receptors that have been associated with Th1(Tc1)/Th0 lymphocytes, while CCR3 and CCR4, receptors associated with Th2 (Tc2)lymphocytes, CCR7, CXCR1 and CXCR2 were not expressed. CXCR3 and CCR5 receptors were functional, as LPL and IEL migrated to their respective ligands I-TAC and RANTES. In addition, most alphaEbeta7- LPL and IEL expressed high levels of CCR2. While the majority of CD45RO(-)beta7hi PBL also expressed CXCR3 and CCR5, a proportion of these cells were CXCR3- and/or CCR5- and some expressed CCR4 and/or CCR7, indicating that lymphocytes recruited to the intestinal mucosa represent a subset of these cells. In summary, our results show that LPL and IEL within the normal intestine express a specific and similar array of chemokine receptors whose ligands are constitutively expressed in the intestinal mucosa and whose expression is up-regulated during intestinal inflammation. These results support the view that CXCR3, CCR5 and CCR2 may play an important role in lymphocyte localization within the intestinal mucosa.

Animals↗
PubMed2000

Beta7 integrin-deficient mice: delayed leukocyte recruitment and attenuated protective immunity in the small intestine during enteric helminth infection.

The ontogeny and function of gut-associated-lymphoid tissue is known to be critically dependent on the beta7 integrin subfamily. We have investigated the development of intestinal inflammation and pathogen-specific protective immunity to enteric helminth infection in beta7 integrin knockout (KO) mice. During Trichinella spiralis infection of the small intestine there was a significant delay and reduction in the magnitude of intestinal eosinophilia and mastocytosis in the absence of P7 integrin, resulting in impaired host protection. Aberrant distribution of mast cells was also observed in the small intestine of infected KO mice. Adoptive transfer of primed wild-type mesenteric lymph node cells into T. spiralis-infected beta7 KO mice did not restore the intestinal mast cell response, suggesting that the defect in intestinal mastocytosis is due to the absence of beta7 expression on this population rather than an indirect consequence of reduced T cell numbers. In contrast, no impairment in leukocyte recruitment or protection against Trichuris muris infection of the large intestine was observed in KO mice. Taken together the data provide the first description of reduced leukocyte homing and attenuated protective immunity against helminth infection in beta7 KO mice. Furthermore, these results suggest that beta7 integrin-independent adhesion molecule interactions are deployed in the large but not small intestine during intestinal inflammation.

Animals↗
PubMed2002

Neonatal infection with a milk-borne virus is independent of beta7 integrin- and L-selectin-expressing lymphocytes.

Mouse mammary tumor virus (MMTV) is acquired by neonates through milk and first infects lymphocytes in Peyer's patches. We show here that newborn mice lacking beta7 integrin or L-selectin were infected with MMTV at wild-type levels in both their lymphoid and mammary tissues. Superantigen-mediated activation and cognate T cell deletion were also unimpaired in both types of null mice. A large proportion of neonatal Peyer's patch lymphocytes in wild-type mice were beta7 and beta1 integrin low and both populations increased in response to MMTV infection. These results suggest that adhesion molecules other than beta7 integrin or L-selectin play a role in lymphocyte homing in the gut, peripheral lymph nodes and mammary gland in response to MMTV infection.

Animals↗
PubMed1995

Alpha E beta 7 and alpha 4 beta 7 integrins associated with intraepithelial and mucosal homing, are expressed on macrophages.

The two beta 7 integrins alpha E beta 7 and alpha 4 beta 7 are the most recently described members of the integrins participating in intercellular binding. Their expression has been shown to be restricted to leukocytes and they have been suggested to be predominantly found in lymphocytes associating with the epithelium. Expression of beta 7 has mainly been studied on lymphocytes whereas macrophages have been reported not to express the beta 7 integrins. In this paper we have studied the expression of beta 7 integrins in monocytoid cells. The myelomonocytic cell lines HL-60 and THP-1 did not express beta 7 mRNA or protein, but differentiation of these cell lines to macrophages with phorbol 12-myristate 13-acetate (PMA) led to a strong induction of the beta 7 mRNA expression. A clear but less pronounced up-regulation of beta 7 mRNA-expression was also seen after treatment of HL-60 and THP-1 cells with interferon-gamma (IFN-gamma). However, its up-regulating effect on the surface expression of alpha 4 beta 7 and alpha E beta 7 complexes (detected by the monoclonal antibodies Act I and HML-1, respectively) exceeded that observed with PMA. To verify the in vitro cell line observations with normal cells, we also studied peripheral blood monocytes and tissue macrophages. Peripheral blood monocytes were Act I- and HML-1- in flow cytometry, but their expression was increased after a 72-h culture in the presence of PMA or IFN-gamma. Also, several Act I+ and HML-1+ macrophages were found in immunohistochemical stainings of both liver and edemic lung biopsies as well as in lymph node sinuses. We therefore conclude that while monocytes do not express beta 7 integrins the more differentiated cells of the monocyte-macrophage lineage do express both the alpha 4 beta 7 and alpha E beta 7 integrins, which might play a role in their intraepithelial homing.

Antibodies, Monoclonal↗
PubMed1996

Phenotype, and migration properties of three major subsets of tissue homing T cells in sheep.

T cells show a bias in their migration pathways: some T cells preferentially migrate to peripheral lymph nodes (LN), some to mucosal tissues, and some to peripheral tissues such as skin. These recirculation pathways were examined in sheep by collecting lymph draining into and out of peripheral and intestinal LN, and using fluorescent dyes to trace the recirculation of the lymph cells. Monoclonal antibodies (mAb) to alpha 4, beta 1, and beta 7 integrins, and L-selectin, were used to define three major populations of recirculating T cells. Naive-type T cells (L-selectin+, alpha 4 beta 1lo beta 7lo) migrated preferentially through peripheral LN. Two memory populations could be defined: alpha 4 beta 1hi beta 7- and alpha 4 beta 7hi beta 1lo. alpha 4 beta 1hi beta 7- T cells were present in lymph draining from the skin. T cells migrating preferentially through intestinal LN were alpha 4 beta 7hi beta 1lo. Consistent with this migration pattern, the endothelial receptor for alpha 4 beta 7, mucosal addressin cell adhesion molecule-1 (MAdCAM-1) was detected on high endothelial venules within intestinal LN and Peyer's patches, but only weakly on high endothelial venules within peripheral LN. Thus, there are at least three easily definable subsets of T cells, based on integrin expression, which show distinct migration preferences.

Animals↗
PubMed2001

Molecular characterization of cell substratum attachments in human glial tumors relates to prognostic features.

Glioma cell attachments to substratum play crucial roles in the invasion by glioma cells of normal brain tissue. These attachments are mediated through interactions between extracellular matrix (ECM) components, integrins, focal adhesion-linked molecules, and the actin cytoskeleton. In the present study, we investigate the molecular elements involved in cell substratum attachments in human glial tumors and their potential relationships to prognostic features. We used 10 human glioma cell lines, for which we characterized glial differentiation by means of quantitative RT-PCR for nestin, vimentin, and GFAP mRNA. We quantitatively determined the amounts of laminin, fibronectin, vitronectin, and thrombospondin secreted by these glioma cell lines in vitro, as well as the amount of each of the eight beta integrin subunits and the adhesion complex-related molecules, including talin, vinculin, profilin, zyxin, alpha-actinin, paxillin, and VASP. After quantification of the levels of migration and invasion of these 10 cell lines in vitro and, through grafts into the brains of nude mice, of their biological aggressiveness in vivo, it appeared that the levels of the beta 5 integrin subunit and alpha-actinin were directly related to biological aggressiveness. These experimental data were clinically confirmed because increasing immunohistochemical amounts of the beta 5 integrin subunit and alpha-actinin were directly related to dismal prognoses in the case of astrocytic tumors. In addition, we show that the beta 4 integrin subunit are expressed significantly more in oligodendrogliomas than in astrocytic tumors. A potential role for the beta 8 integrin subunit in glioma cell substratum attachments is also emphasized.

Actinin↗
PubMed2002

Integrin expression in colon cancer cells is regulated by the cytoplasmic domain of the beta6 integrin subunit.

We have previously reported that the alphavbeta6 integrin upregulates its own expression in a protein kinase C-dependent manner with increasing cell density. The wild-type beta6 integrin subunit has also been shown to promote tumour growth in vivo and its growth-enhancing effect is regulated by both a MAP kinase binding motif on beta6 and the 11 amino acid C-terminal cytoplasmic extension unique to the beta6 subunit. Herein, we show that the 11 amino acid cytoplasmic extension is essential for the cell density-dependent increase in beta6 expression and that the 11 amino acid tail exerts a dominant negative effect on cell density- and PKC-mediated beta5 expression in alphavbeta6-expressing colon cancer cells. Cells that express beta6 lacking the 11 amino acid tail respond to PKC simulation with increased expression of only the beta5 subunit as seen for cells that lack constitutive alphavbeta6 expression. In contrast, loss of the ERK binding site on beta6 markedly impairs cell density- and PKC-dependent expression of either beta6 or beta5 in the presence or absence of the 11 amino acid tail, respectively. Our findings suggest that in alphavbeta6-expressing cells, a hierarchy of kinase signalling cascades exists and that the beta6-ERK2 interaction dominates over PKC-mediated signalling pathways responsible for integrin upregulation with cell confluence. Given the dominance of the beta6-ERK2 interaction over PKC-mediated expression of both beta5 and beta6 integrin subunits, targeting the beta6-ERK2 interaction may prove useful as an anticancer strategy in colon cancer.

Amino Acid Motifs↗
PubMed2003

Lamellipodial motility in wounded endothelial cells exposed to physiologic flow is associated with different patterns of beta1-integrin and vinculin localization.

Integrins- and cytoskeletal-associated focal adhesion proteins may participate in the process of endothelial wound closure, but their relationship in these wounds and in the presence of shear forces has not been defined. The goal in this study was to test the hypotheses that (1) modulation of beta(1)-integrin in human coronary artery endothelial cells (HCAEC) would alter endothelial wound closure under shear stress, and (2) beta(1)-integrin association with vinculin would be necessary for mediating this closure. HCAEC monolayers were pre-conditioned to attain alignment by shearing at 12 dynes/cm(2) for 18 h in a parallel-plate flow chamber. Subsequently, they were divided into three groups: (a) control, (b) treated with anti-beta(1)-integrin adhesion blocking antibody, or (c) treated with anti-beta(1)-integrin adhesion promoting antibody. Next, the monolayers were wounded with a metal spatula, and re-sheared at 20 dynes/cm(2) or left static. Time-lapse imaging and deconvolution microscopy were then performed for 3 h. Immunocytochemistry for beta(1)-integrin expression and vinculin was performed on all wounded monolayers. Under shear stress, vinculin localized to the ends of stress fibers, while beta(1)-integrin took on an intracellular macroaggregate appearance. Treatment with anti-beta(1)-integrin adhesion blocking antibody enhanced wound closure, left the vinculin staining at the lamellipodial tips unchanged, but was associated with beta(1)-integrin staining at the lateral cell edges. Treatment with the anti-beta(1)-integrin adhesion promoting antibody retarded wound closure, increased vinculin staining at cell-cell junctions, and was associated with a fibrillar pattern of beta(1)-integrin staining. Modulation of beta(1)-integrin and changes in beta(1)-integrin and vinculin localization may further our understanding of laminar shear stress-induced endothelial repair in the coronary circulation.

Antibodies, Monoclonal↗
PubMed2002

Annexin-V binds to the intracellular part of the beta(5) integrin receptor subunit.

Bovine lactadherin binds to the alpha(v)beta(3) and alpha(v)beta(5) integrins in an RGD-dependent manner and also to anionic phospholipids. During the affinity purification of lactadherin binding receptors, a 35-kDa protein persistently coeluted with the alpha(v)beta(5) integrin receptor. Subsequently, peptide mapping, amino acid sequencing, and mass spectrometry analysis identified this protein as bovine annexin-V. Annexin-V accompanied the integrin receptor eluted with either RGD peptide or with EDTA suggesting that annexin-V bound specifically to the alpha(v)beta(5) integrin. To further investigate this putative interaction of annexin-V with the alpha(v)beta(5) integrin receptor, human annexin-V and intracellular domains of the human alpha(v)beta(5) integrin subunits were used in ligand blotting assays. Radiolabeled annexin-V showed weak binding to the intracellular part of beta(5) integrin subunit. However, by adding the aminophospholipid, phosphatidyl serine, the interaction with the beta(5) cytoplasmic peptide was enhanced many fold. Furthermore, the interaction was shown to be independent of phosphorylation, as annexin-V bound to unphosphorylated beta(5) peptide at a similar level to the phosphorylated peptide. Since binding of annexin-V to the alpha(v) integrin subunit tail was not detected, annexin-V was shown to associate specifically with the beta(5) cytoplasmic tail. Together these findings suggest a novel link between annexins and the integrin receptor family.

Amino Acid Sequence↗
PubMed1995

Beta 7 integrins and other cell adhesion molecules are differentially expressed and modulated by TNF beta in different lymphocyte populations.

To explore the role of beta 7 integrins subfamily and TNF beta in intestinal mucosal immunity and disease, we have examined the expression and modulation by TNF beta of beta 7 integrins and other cell adhesion molecules on mouse intestinal lymphocytes. Most of the small intestine intraepithelial lymphocytes (SIEL) and lamina propria lymphocytes (LPL) were M293 (beta 7) and M290 (alpha M290 beta 7) positive, whereas only 10-20% of SIEL and approximately 50% of LPL were R1-2 (alpha 4 beta 1/alpha 4 beta 7) positive. Only the expression of the R1-2 integrin was downregulated by TNF beta on SIEL. In contrast, expression of R1-2 was unaffected and expression of M290 was partially down-regulated by TNF beta on LPL. About 2-3% of spleen lymphocytes (SL) were M293, M290, and R1-2 positive, and on these cells expression of M290 (and M293) was strongly induced by TNF beta. CD45 expression was partially downregulated by TNF beta on SIEL, LPL, and SL, whereas the expression of ICAM-1 and CD45RB was upregulated by TNF beta only on SIEL. TNF beta strongly downregulated CD44 expression on SIEL, upregulated CD44 expression on LPL, and had no effect on CD44 on SL. These phenotypic differences and different responses to TNF beta modulation between SIEL, LPL, and SL may reflect differences in the microenvironments in which these cells reside and imply that SIEL and LPL may play different roles in intestinal immunity. Further, TNF beta may play an important role in regulating the function of beta 7 integrins and other cell adhesion molecules.

Animals↗
PubMed1995

Expression of beta 7 integrins and other cell adhesion molecules on mouse lymphocytes and their modulation by a new cytokine, IL-2 receptor-inducing factor.

We explored the role of a new cytokine, IL-2 receptor-inducing factor (IL-2RIF), in intestinal mucosal immunity and in the regulation of integrin beta 7 receptors on intestinal lymphocytes. Most SIEL (small intestine intraepithelial lymphocytes) were M290 (alpha M290 beta 7) positive, while only 10 to 15% of SIEL were R1-2 (alpha 4) positive. The expression of alpha 4 (R1-2) and beta 7 (M293) but not alpha M290 beta 7 integrin on SIEL was up-regulated by IL-2RIF. Incubating SIEL with IL-2RIF resulted in the up-regulation of CD45RB and down-regulation of CD44. About 50% of LPL (lamina propria lymphocytes) were alpha M290 beta 7 positive, while only 20% of LPL were alpha 4 positive. The expression of alpha M290 beta 7 integrin on LPL was down-regulated and alpha 4 and beta 7 integrin was up-regulated by IL-2RIF. Incubating LPL with IL-2RIF resulted in the up-regulation of CD44 and no significant change of CD11a, CD45, CD45RB, and ICAM-1. These results suggested that SIEL and LPL may play a different role in intestinal mucosal immunity and that IL-2RIF may play an important role in regulating the functions of integrins beta 7 on IEL and LPL.

Adjuvants, Immunologic↗
PubMed1997

Cloning and characterization of novel beta integrin subunits from a sea urchin.

Cell surface molecules that mediate adhesion in sea urchin embryos have been implicated in morphogenesis, and yet the molecules remain largely uncharacterized. Here we report evidence from PCR amplification for three novel beta integrin subunits that are expressed during early development of Strongylocentrotus purpuratus. The full cDNA sequence for one of these, betaG, bears a 59% similarity to Drosophila betaPS and a 58% similarity to vertebrate integrins. betaG closely resembles the beta1 subunit of vertebrates, particularly in the cytoplasmic domain where amino acids of the human beta1 subunit implicated in cell adhesion and signaling are conserved. The betaG subunit is detectable as a maternal, 7.5-kb transcript in eggs and expression peaks during gastrulation. Immunoblots with antiserum raised against a bacterially expressed fragment of the betaG subunit have bands with apparent molecular weights of about 130 kDa under reducing conditions and 110 kDa under nonreducing conditions. Immunoprecipitations suggest that betaG associates with at least two alpha subunits in gastrula stage embryos. In situ RNA hybridization of the betaG subunit indicates that all cells of the embryo express this molecule prior to gastrulation. In gastrulae, hybridization of the probe is highest in primary mesenchyme, secondary mesenchyme, the developing gut, and pigment cells. In immunolocalizations all cells of the blastulae express the protein at low levels and primary mesenchyme cells express betaG after they enter the blastocoel. Expression of the protein appears to be downregulated in the archenteron throughout gastrulation. betaG protein expression is also evident on secondary mesenchyme as they ingress and migrate in the blastocoel. We conclude that sea urchin embryos express integrins that are structurally similar to those characterized in other animals. Because betaG is expressed by migrating mesenchyme and yet is downregulated by rearranging epithelia, we suggest that this subunit has several functions during early development.

Amino Acid Sequence↗
PubMed1998

The betaL integrin subunit is necessary for gastrulation in sea urchin embryos.

Integrins are a family of cell adhesion molecules reported to mediate cellular interactions essential for normal embryonic morphogenesis. Here we describe a beta integrin subunit that is expressed during early embryogenesis in the sea urchin embryo and appears to be necessary for normal development. The deduced amino acid sequence of betaL is similar to vertebrate beta integrin subunits, but is most closely related to the sea urchin betaG subunit. Northern blots show that betaL is expressed at all stages with maximum expression beginning during gastrulation. Immunolocalization and in situ RNA hybridization show that in blastulae betaL is expressed in the blastoderm and by the ring of bottle cells in the vegetal plate during the initial phase of gastrulation. Presumptive secondary mesenchyme cells express high levels of betaL throughout elongation of the archenteron and in the pluteus betaL is expressed by blastocoelar cells, skeletal mesenchyme, and pigment cells. Antibodies and Fab fragments against betaL block spreading of dissociated embryonic cells on RGD (arginine-glycine-aspartate)-containing substrates. Treating embryos with anti-betaL antibodies blocks the initial phase of gastrulation and interferes with the organization of actin filaments. Prior to gastrulation, the antibodies cause thickening of the blastoderm and later in development defects in skeletal patterning result. Probing for antibody in treated embryos indicates that it penetrates the ectoderm to cells within the blastocoel and is actively endocytosed. We propose that betaL forms receptors that bind to RGD-containing ligands and anchors actin filaments. These receptors appear to be essential in several aspects of morphogenesis.

Amino Acid Sequence↗
PubMed1997

alphaV Integrins on HT-29 colon carcinoma cells: adhesion to fibronectin is mediated solely by small amounts of alphaVbeta6, and alphaVbeta5 is codistributed with actin fibers.

HT-29 colon carcinoma cells form liver metastases upon intrasplenic injection, and adhesion to fibronectin under the liver microvascular liver endothelium is likely to be important for metastasis formation. We have therefore studied the integrins involved in fibronectin adhesion. This was not affected by blocking antibodies against the beta1, alpha3, and alpha5 integrin subunits, but it was blocked by an RGD-containing peptide, indicating involvement of RGD-dependent non-beta1 alphaV integrins. Both alphaVbeta5 and alphaVbeta6 were detected on HT-29 cells. Blocking mAb against alphaV, but not against alphaVbeta5, abolished adhesion. From a HT-29 cell lysate, only alphaVbeta6 bound to a fibronectin-Sepharose column. Thus, alphaVbeta6 is the main fibronectin receptor on HT-29 cells, despite the very low levels of alphaVbeta6 and the much higher levels of alphaVbeta5. The HT29 cells did not spread on fibronectin in the absence of serum, not even after a three- to fourfold increase in alphaVbeta6 levels, induced by interleukin 4. The cells did spread on vitronectin. Using immunofluorescence we observed that both on vitronectin and on fibronectin alphaVbeta5 was arranged in a striped pattern, aligned with actin fibers, and not in focal adhesions. On fibronectin, but not on vitronectin, alphaVbeta6 was concentrated in a punctate pattern at the periphery of cell islands.

Actins↗
PubMed1994

Regional localization of the human integrin beta 6 gene (ITGB6) to chromosome 2q24-q31.

The heterodimer alpha v beta 6 acts as a fibronectin receptor for human carcinoma cells. We report here the regional localization of the beta 6 gene to 2q24-q31 by fluorescence in situ hybridization coupled with GTG-banding. This gene is located close to the region to which genes coding for the alpha subunits of the integrins VLA-4 and vitronectin receptor (ITGA4 and ITGAV, respectively) have been previously mapped (2q31-q32). These data suggest a proximal position of the integrin beta 6 locus (ITGB6) on this integrin gene cluster. Furthermore, double-labeling in situ hybridization experiments performed with alpha 4 and alpha v probes indicated a telomeric position of ITGAV with respect to ITGA4.

Chromosome Banding↗
PubMed2001

Expression and cellular distribution of alpha(v)integrins in beta(1)integrin-deficient embryonic stem cell-derived cardiac cells.

beta(1)integrin-deficient (beta(1)-/-) ES cells showed increased differentiation of cardiac cells characterized by reduced adhesion and high beating frequency. Whereas in whole embryoid body outgrowths of beta(1)-/- cells maximum levels of alpha(v), beta(3)and beta(5)integrin mRNA were delayed and transiently upregulated, in cardiac clusters isolated from beta(1)-/- cells, only beta(3)integrin mRNA levels were enhanced in comparison to wild-type (wt) cells. To answer the question, whether alpha(v)and beta(3)integrins may compensate, at least partially, the loss of beta(1)integrin function during cardiac differentiation, the distribution of alpha(v)and beta(3)integrins in beta(1)-/- and wt pacemaker-like cardiac cells was analyzed. A different distribution of alpha(v)and beta(3)integrins in beta(1)-/- v wt cardiac cells was found. In wt cardiac cells, beta(1)integrin was localized in specialized subsarcolemmal regions, in particular, at focal contacts and costameres, but alpha(v)integrin was diffusely distributed. In contrast, in beta(1)-/- cardiac cells, alpha(v)integrin was preponderantly localized at cell membranes, focal contacts and costameres. beta(3)integrin displayed a diffuse pattern both in wt and in beta(1)-/- pacemaker-like cells at early differentiation stages, whereas at terminal stages, beta(3)was colocalized with sarcomeres in wt, but not in beta(1)-/- pacemaker-like cells. Quantitative immunofluorescence analysis revealed increased alpha(v)and beta(3)integrin levels in beta(1)-/- pacemaker-like cardiac cells. Our results led us to conclude that altered cellular distribution of alpha(v)integrin and upregulation of beta(3)integrin correlate with growth and survival of beta(1)-/- cardiac pacemaker-like cells at an early developmental state. However, alpha(v)and beta(3)integrins cannot functionally compensate the loss of beta(1)integrin during terminal differentiation of cardiac cells implicating that cardiomyocytes require specific beta(1)integrin functions for cardiac specialization.

Animals↗