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PubMed2006

Collagen XVI harbors an integrin alpha1 beta1 recognition site in its C-terminal domains.

Collagen XVI is integrated tissue-dependently into distinct fibrillar aggregates, such as D-banded cartilage fibrils and fibrillin-1-containing microfibrils. In skin, the distribution of collagen XVI overlaps that of the collagen-binding integrins alpha1 beta1 and alpha2 beta1. Basal layer keratinocytes express integrin alpha2 beta1, whereas integrin alpha1 beta1 occurs in smooth muscle cells surrounding blood vessels, in hair follicles, and on adipocytes. Cells bearing the integrins alpha1 beta1 and alpha2 beta1 attach and spread on recombinant collagen XVI. Furthermore, collagen XVI induces the recruitment of these integrins into focal adhesion plaques, a principal step in integrin signaling. Of potential physiological relevance, these integrin-collagen XVI interactions may connect cells with specialized fibrils, thus contributing to the organization of fibrillar and cellular components within connective tissues. In cell-free binding assays, collagen XVI is more avidly bound by alpha1 beta1 integrin than by alpha2 beta1 integrin. Both integrins interact with collagen XVI via the A domain of their alpha subunits. A tryptic collagen XVI fragment comprising the collagenous domains 1-3 is recognized by alpha1 beta1 integrin. Electron microscopy of complexes of alpha1 beta1 integrin with this tryptic collagen XVI fragment or with full-length collagen XVI revealed a unique alpha1 beta1 integrin-binding site within collagen XVI located close to its C-terminal end.

Adipocytes↗
PubMed1998

Inhibition of BCR-ABL expression with antisense oligodeoxynucleotides restores beta1 integrin-mediated adhesion and proliferation inhibition in chronic myelogenous leukemia hematopoietic progenitors.

Chronic myelogenous leukemia (CML) is characterized by the continuous proliferation and abnormal circulation of malignant hematopoietic progenitors. This may be related to the unresponsiveness of CML progenitors to beta1 integrin adhesion receptor-mediated inhibition of progenitor proliferation by the marrow microenvironment. In hematopoietic cell lines, the BCR-ABL oncogene product, p210(BCR-ABL), interacts with a variety of cytoskeletal elements important for normal integrin signaling. We studied the role of p210(BCR-ABL) in abnormal integrin function in CML by evaluating the effect of inhibition of BCR-ABL expression with antisense oligodeoxynucleotides (AS-ODNs) on integrin-mediated adhesion and proliferation inhibition of malignant primary progenitors from CML marrow. Preincubation of CML CD34(+)HLA-DR+ (DR+) cells with breakpoint-specific AS-ODNs significantly increased adhesion of CML progenitors to stroma and fibronectin (FN). Pretreatment with breakpoint-specific ODNs also resulted in significant inhibition of CML progenitor proliferation after ligand or antibody-mediated beta1 integrin engagement. Breakpoint-specific ODNs were significantly more effective in restoring CML progenitor adhesion and proliferation inhibition than control ODNs. BCR-ABL mRNA and p210(BCR-ABL) levels in CML CD34(+) cells were significantly reduced after incubation with breakpoint-specific AS-ODN. These studies indicate a role for BCR-ABL in abnormal circulation and defective integrin-dependent microenvironmental regulation of proliferation of CML hematopoietic progenitors.

Cell Adhesion↗
PubMed2001

Co-localization of integrins and matrix metalloproteinases in the extracellular matrix of chondrocyte cultures.

Beta1-integrins were found in the cartilage matrix, suggesting their implication in the assembly of its architectural scaffold, but the mechanism for this event is not yet clear. Matrix metalloproteinases (MMPs) may be involved in an integrin-shedding mechanism and matrix beta1-integrins may act to alter MMP activity. To begin to address this question, this study was designed to determine whether beta1-integrins and MMPs are colocalized in the chondrocytes or in the extracellular matrix of cartilage. We investigated high-density cultures of limb buds of 12-day-old mouse embryos by double immunofluorescence, immunoelectron microscopy and by coimmunoprecipitation assays in order to examine the localization of beta1-integrins and matrix metalloproteinases (MMP-1, MMP-3 and MMP-9) in cartilage. It was found, that all investigated MMPs and beta1-integrins were specifically co-localized in high-density cartilage cultures. Immunogold and immunofluorescence labelling of both beta1-integrins and MMPs were observed not only at the surface of chondrocytes but mainly also in the pericellular space and distributed between collagen fibrils in the extracellular matrix (ECM) as well. Results of immunoprecipitation experiments suggest a functional association of MMPs and beta1-integrins in chondrocytes as already described for other cell types. Further investigations are needed to elucidate the functional association between beta1-integrins and MMPs in chondrocytes.

Animals↗
PubMed2004

Integrin chains beta1 and alphav as prognostic factors in human metastatic melanoma.

The expression pattern of integrin-type cell adhesion receptors is often changed during malignant transformation. In the present work, we studied the prognostic significance of beta1 and alphav integrin chains for survival of patients with metastatic melanoma. The expression levels of beta1 integrin were also compared with those of Bcl-2, an anti-apoptotic protein, the presence of which is associated with treatment response and survival in melanoma. The expression of beta1 and alphav integrins in 68 melanoma metastases obtained from 55 patients treated with combined chemoimmunotherapy was studied by immunohistochemistry using anti-beta1 and anti-alphav antibodies. The patients were divided into two groups (using a cut-off point of >/= 81%) for beta1 integrin expression levels and into three categories (negative/low, median, high) for alphav integrin expression levels. All tumours were positive for beta1 integrin, and the tumours (n = 6) which had the highest alphav score were also strongly positive for beta1 (94%; P = 0.0055). Patients (n = 43) with 80% or less beta1 integrin-positive tumour cells in their samples had a median disease-free survival (DFS) of 17.0 months, and patients (n = 12) with 81% or more beta1 integrin-positive tumour cells had a DFS of only 5.7 months (P = 0.0001). Patients (n = 32) with low alphav integrin expression levels had shorter DFS (median 12.3 months; P = 0.0146) than patients (n = 20) with median expression levels (median 16.7 months; P = 0.0146). However, three patients who had a very strong alphav expression in their tumours had a median DFS of only 1.8 months (P = 0.0146). Median level expression of beta1 integrin was associated with the presence of Bcl-2 in tumour cells (P = 0.0033). Our results suggest that beta1 and alphav integrin chains are independently expressed in metastatic melanoma and may have an effect on the metastatic potential of melanoma cells.

Adult↗
PubMed2004

Yersinia enterocolitica adhesin A induces production of interleukin-8 in epithelial cells.

The major invasive factor of Yersinia enterocolitica, the invasin (Inv) protein, induces proinflammatory host cell responses, including interleukin-8 (IL-8) secretion from human epithelial cells, by engagement of beta1 integrins. The Inv-triggered beta1 integrin signaling involves the small GTPase Rac; the activation of MAP kinases, such as p38, MEK1, and JNK; and the activation of the transcription factor NF-kappaB. In the present study, we demonstrate that Y. enterocolitica YadA, which is a major adhesin of Y. enterocolitica with pleiotropic virulence effects, induces IL-8 secretion in epithelial cells. The abilities of YadA and Inv to promote adhesion to and invasion of HeLa cells and to induce IL-8 production by the cells were investigated by expression of YadA and Inv in Escherichia coli. While YadA mediates efficacious adhesion to HeLa cells, it mediates marginal invasion compared with Inv. Both YadA and Inv trigger comparable levels of IL-8 production. Conformational changes of the YadA head domain by mutation of NSVAIG-S motifs, which abolish collagen binding, also abolish adhesion of Yersinia to HeLa cells and YadA-mediated IL-8 secretion. Furthermore, experiments in which blocking antibodies against beta1 integrins were used demonstrate that beta1 integrins are crucial for YadA-mediated IL-8 secretion. Inhibitor studies demonstrate the involvement of small GTPases and MAP kinases, such as p38, MEK1, and JNK, indicating that beta1 integrin-dependent signaling mediated by Inv or YadA involves similar signaling pathways. These data present YadA, in addition to Inv, YopB, and Yersinia lipopolysaccharide, as a further inducer of proinflammatory molecules by which Y. enterocolitica might promote inflammatory tissue reactions.

Adhesins, Bacterial↗
PubMed2003

Arf6 and phosphoinositol-4-phosphate-5-kinase activities permit bypass of the Rac1 requirement for beta1 integrin-mediated bacterial uptake.

Efficient entry of the bacterium Yersinia pseudotuberculosis into mammalian cells requires the binding of the bacterial invasin protein to beta1 integrin receptors and the activation of the small GTPase Rac1. We report here that this Rac1-dependent pathway involves recruitment of phosphoinositol-4-phosphate-5-kinase (PIP5K) to form phosphoinositol-4,5-bisphosphate (PIP2) at the phagocytic cup. Reducing the concentration of PIP2 in the target cell by using a membrane-targeted PIP2-specific phosphatase lowered bacterial uptake proportionately. PIP2 formation is regulated by Arf6. An Arf6 derivative defective for nucleotide binding (Arf6N122I) interfered with uptake and decreased the level of PIP2 around extracellular bacteria bound to host cells. This reduction in PIP2 occurred in spite of fact that PIP5K appeared to be recruited efficiently to the site of bacterial binding, indicating a role for Arf6 in activation of the kinase. The elimination of the Rac1-GTP-bound form from the cell by the introduction of the Y. pseudotuberculosis YopE RhoGAP protein could be bypassed by the overproduction of either PIP5K or Arf6, although the degree of bypass was greater for Arf6 transfectants. These results indicate that both Arf6 and PIP5K are involved in integrin-dependent uptake, and that Arf6 participates in both activation of PIP5K as well as in other events associated with bacterial uptake.

ADP-Ribosylation Factor 6↗
PubMed2005

The CXCR1 tail mediates beta1 integrin-dependent cell migration via MAP kinase signaling.

In this study, we examined how IL-8 induces leukocyte migration on major beta1 integrin ligands derived from the extracellular matrix protein fibronectin. We assessed individual contributions of signaling by IL-8 receptors by transfection of CXCR1 and CXCR2 into rat basophilic leukemia (RBL) cells and human monocytic THP-1 cells. CXCR1 expressing cells migrated on the fibronectin ligands for alpha4beta1 and alpha5beta1 integrins in response to IL-8, whereas CXCR2 expressing cells did not. RBL cells expressing the chimeric CXCR1 receptor containing the cytoplasmic tail of CXCR2 had greatly blunted migration, while cells expressing the CXCR2 chimera with the tail of CXCR1 had augmented migration. Last, inhibitors of p38 and JNK MAP kinases blocked IL-8-induced migration in CXCR1+ cells. We conclude that IL-8 stimulated beta1 integrin-mediated leukocyte migration on fibronectin through CXCR1 is dependent on the C-terminal cytoplasmic domain of CXCR1 and subsequent p38 and JNK MAPK signaling.

Animals↗
PubMed2002

Integrin expression in the dermis during scar formation in humans.

To evaluate changes leading to human wound reorganization we examined by immunohistochemistry the expression of several extracellular matrix (ECM) receptors (alpha2 chain of VLA-2, alpha3 chain of VLA-3, alpha6 chain of VLA-6, alphav, and beta1/beta3 chains of integrins) in a series of biopsies of human skin wounds healing by primary intention. The first time point investigated in this study was day 6 after injury, i.e. when a fibrin clot has been almost completely replaced by the granulation tissue. Gradual changes in integrin expression in granulation tissue and in the dermal scar were observed from the first time point investigated and were characterized by an up-regulation of alpha2beta1 complex, alphav integrin subunit, and beta1 integrin subunit. At day 27, the expression of the alpha2 chain of VLA-2 in the scar decreased. The expression of alphav and beta1 integrin subunits decreased but was still detectable by day 35. Vitronectin expression from day 7 onwards was also increased and colocalized to the area of the wounded dermis, and decreased by day 27. Our data suggests that, during the remodelling of the provisional matrix of the wound, dermal fibroblasts express transiently mainly alpha2 and alphav subunits of integrins associated with up-regulation of the beta1 subunit. It seems that up-regulation of some chains of integrins may be involved in the control of deposition of ECM components associated with wound healing.

Cicatrix↗
PubMed2001

Sequence-specific interaction between the disintegrin domain of mouse ADAM 3 and murine eggs: role of beta1 integrin-associated proteins CD9, CD81, and CD98.

ADAM 3 is a sperm surface glycoprotein that has been implicated in sperm-egg adhesion. Because little is known about the adhesive activity of ADAMs, we investigated the interaction of ADAM 3 disintegrin domains, made in bacteria and in insect cells, with murine eggs. Both recombinant proteins inhibited sperm-egg binding and fusion with potencies similar to that which we recently reported for the ADAM 2 disintegrin domain. Alanine scanning mutagenesis revealed a critical importance for the glutamine at position 7 of the disintegrin loop. Fluorescent beads coated with the ADAM 3 disintegrin domain bound to the egg surface. Bead binding was inhibited by an authentic, but not by a scrambled, peptide analog of the disintegrin loop. Bead binding was also inhibited by the function-blocking anti-alpha6 monoclonal antibody (mAb) GoH3, but not by a nonfunction blocking anti-alpha6 mAb, or by mAbs against either the alphav or beta3 integrin subunits. We also present evidence that in addition to the tetraspanin CD9, two other beta1-integrin-associated proteins, the tetraspanin CD81 as well as the single pass transmembrane protein CD98 are expressed on murine eggs. Antibodies to CD9 and CD98 inhibited in vitro fertilization and binding of the ADAM 3 disintegrin domain. Our findings are discussed in terms of the involvement of multiple sperm ADAMs and multiple egg beta1 integrin-associated proteins in sperm-egg binding and fusion. We propose that an egg surface "tetraspan web" facilitates fertilization and that it may do so by fostering ADAM-integrin interactions.

ADAM Proteins↗
PubMed2002

The integrin alpha(v)beta8 mediates epithelial homeostasis through MT1-MMP-dependent activation of TGF-beta1.

Integrins, matrix metalloproteases (MMPs), and the cytokine TGF-beta have each been implicated in homeostatic cell behaviors such as cell growth and matrix remodeling. TGF-beta exists mainly in a latent state, and a major point of homeostatic control is the activation of TGF-beta. Because the latent domain of TGF-beta1 possesses an integrin binding motif (RGD), integrins have the potential to sequester latent TGF-beta (SLC) to the cell surface where TGF-beta activation could be locally controlled. Here, we show that SLC binds to alpha(v)beta8, an integrin expressed by normal epithelial and neuronal cells in vivo. This binding results in the membrane type 1 (MT1)-MMP-dependent release of active TGF-beta, which leads to autocrine and paracrine effects on cell growth and matrix production. These data elucidate a novel mechanism of cellular homeostasis achieved through the coordination of the activities of members of three major gene families involved in cell-matrix interactions.

Animals↗
PubMed1997

Regulation of tumor cell motility and migration by CD63 in a human melanoma cell line.

CD63 belongs to the transmembrane 4 superfamily of membrane proteins and is expressed in several normal tissues as well as in melanoma cells. Previous reports have suggested that CD63 may play an important role in inhibiting melanoma progression, and this was supported by our studies showing that CD63 was associated with suppression of the growth of melanoma in nude mice. Recently, we and others have shown that CD63 may form noncovalent associations with beta1 integrins, which suggests that the function of CD63 may be related to that of integrins. To further explore the role of CD63 in melanoma, we transfected CD63 into a highly motile, CD63-negative melanoma cell line, KM3, which was shown to express alpha(v)beta5 as the predominant integrin with only trace amounts of beta1 integrins. Following transfection, CD63 was shown to associate with beta1 integrins, and beta1 expression appeared to be up-regulated. Cell motility in serum-containing media was markedly suppressed following transfection of CD63. This inhibition was potentiated by mAbs to CD63, and correlated with the level of CD63 expression. The CD63-transfected, but not the untransfected, melanoma cells showed increased adhesion and migration on the beta1 substrates, fibronectin, laminin, and collagen, whereas rates of migration were similar on the beta5 substrate, vitronectin. These results show that CD63 is involved in regulation of the motility of melanoma cells and their adhesion and migration on substrates associated with beta1 integrins. We suggest they provide further insights into the role of CD63 in tumor progression.

Antigens, CD↗
PubMed1999

Mutation of a basic sequence in the laminin alpha2LG3 module leads to a lack of proteolytic processing and has different effects on beta1 integrin-mediated cell adhesion and alpha-dystroglycan binding.

A RRKRRQ sequence unique to the LG3 module of the laminin alpha2 chain was previously shown to be sensitive to endogenous proteolysis during the recombinant production of the tandem array alpha2LG1-3. Mutation of RQ surrounding the cleaved peptide bond did not prevent this processing and intracellular degradation. Alanine mutagenesis of three alternate basic residues, however, was shown to prevent the cleavage in alpha2LG1-3, allowing for the alpha2LG3 module to be obtained as a folded, globular fragment. The mutation did not change heparin and sulfatide binding or cell adhesion of alpha2LG1-3 which can be mediated by alpha3beta1 and alpha6beta1 integrins. It did, however, cause a 10-fold reduction in alpha-dystroglycan binding. The data favor the interpretation that binding epitopes for heparin/sulfatides, beta1 integrins and alpha-dystroglycan occupy different parts of the alpha2LG1-3 structure.

Animals↗
PubMed2003

A novel form of integrin dysfunction involving beta1, beta2, and beta3 integrins.

The adhesion receptors known as integrins perform key functions for hematopoietic cells. The platelet integrin alphaIIbbeta3 is critical in hemostasis, and the beta1 and beta2 integrins on leukocytes have many roles in cell-mediated immunity. Mutations in the beta2 subunit lead to integrin nonexpression and to an immune deficiency, leukocyte adhesion deficiency-1. Mutations in either the alpha or beta subunit of alphaIIbbeta3 usually lead to integrin nonexpression and a bleeding tendency termed Glanzmann thrombasthenia. Here we describe a unique patient with clinical features of both Glanzmann thrombasthenia and leukocyte adhesion deficiency-1. The patient has normal expression of beta1, beta2, and beta3 integrins, but all are dysfunctional. The key findings are that "inside-out" signaling pathways leading to integrin activation are defective and that this is associated with abnormal integrin clustering. The integrins themselves are intact and capable of function following extracellular stimulation. T cell motility is normal, as are the expression levels and electrophoretic characteristics of all cytoskeletal and signaling proteins tested, except PKC-alpha, which has enhanced expression in the patient's cells. To our knowledge, this is the first description of a dysfunction affecting three classes of integrins. We propose that it is caused by a lesion in an intracellular factor or signaling pathway essential for integrin activation in hematopoietic cells and results in lack of regulation of clustering, an essential component of integrin-mediated adhesion.

Blood Platelets↗
PubMed2001

Activity of proximal promoter of the human beta(1)-integrin gene was increased in Sézary syndrome.

Changes in beta1-integrin expression have been involved in abnormal cellular interactions between malignant lymphocytes from Sézary (Sz) patients and keratinocytes. In this paper, we compare the activity of both distal and proximal promoters of the beta1-integrin gene in malignant lymphocytes from Sz patients with human normal lymphocytes. Activity of both beta1-integrin promoters was also analysed in human normal keratinocytes. Northern blot analysis shows that beta1-integrin mRNA expression is higher in malignant Sz lymphocytes than in normal lymphocytes. CAT assays show that the activity of proximal beta1-integrin promoter is markedly increased (up to 6-fold) in malignant lymphocytes from Sz patients, in comparison to normal lymphocytes. These results suggest that changes in activity of the proximal promoter of beta1-integrin subunit could be, in part, responsible for the abnormal cellular interactions between malignant lymphocytes and keratinocytes observed in Sz syndrome.

Cells, Cultured↗
PubMed1996

Beta1 integrin-mediated activation of focal adhesion kinase and its association with Fyn and Zap-70 in human NK cells.

Adhesive interactions mediated by cell surface receptors have been shown to induce signal transduction pathways that regulate changes in cellular function. We have reported recently that fibronectin (FN) receptors, alpha4beta1 and alpha5beta1 integrins, on NK cells transduce transmembrane signals leading to tyrosine phosphorylation of 60-, 70-, and 120-kDa proteins. In the current study, we have identified a 120-kDa phosphoprotein as the focal adhesion kinase (p125FAK), a structurally unique nonreceptor protein tyrosine kinase that localizes to focal adhesions. Activity of p125FAK was induced by adhesion of NK cells to plastic-immobilized FN, by cross-linking of cell surface-bound FN or FN fragments, FN120 or FN40, with anti-FN mAb, or by cross-linking of alpha4beta1 or alpha5beta1 integrins with alpha-chain-specific Abs. We also observed that enhanced in vitro kinase activity was associated with immunoprecipitates of alpha4beta1 or alpha5beta1 integrins from lysates of FN-adherent NK cells as compared with BSA-treated NK cells. In addition to p125FAK activity, FN-induced kinase activity was also found to be mediated by Fyn, Lyn, and Zap-70, as assessed by in vitro phosphorylation of the immunoprecipitated kinases in the presence of [gamma-32P]ATP. Clustering of FN receptors on NK cells by agonists such as immobilized FN or alpha4- or alpha5-specific Abs also induced association of Fyn and Zap-70 with p125FAK. Our observations indicate that activation and phosphorylation of p125FAK as well as Zap-70 and certain kinases of the src family play an important role in formation of active signaling complexes in response to triggering via beta1 integrins on NK cells. These results also suggest the existence of cross-talk or points of convergence between the beta1 integrin-mediated and other receptor-signaling pathways.

Cell Adhesion↗
PubMed2005

A hemocyte-specific integrin required for hemocytic encapsulation in the tobacco hornworm, Manduca sexta.

Upon encountering an object recognized as foreign, insect hemocytes aggregate in multiple layers on the surfaces of the object in a process known as encapsulation. For encapsulation to occur, hemocytes must switch from their usual nonadherent state to an adherent state, presumably by regulating the activity of adhesion proteins. Although detailed knowledge exists regarding the adhesion receptors for cells of the mammalian immune system, comparable information on adhesion molecules of insect hemocytes and their function in immune responses is extremely limited. We report here the identification of an integrin present exclusively on the surface of hemocytes in the tobacco hornworm, Manduca sexta. Monoclonal antibodies MS13 and MS34, which bind to plasmatocytes and block encapsulation, were used for immunoaffinity chromatography to isolate their corresponding hemocyte antigen, which was revealed to be the same integrin beta subunit. A cDNA for this M. sexta integrin beta1 was cloned and characterized. Integrin-beta1 mRNA was detected by Northern analysis in hemocytes and not in other tissues tested. MS13 and MS34 were demonstrated to bind to a recombinant fragment of integrin beta1 consisting of the I-like domain, consistent with their blocking of a ligand-binding site and subsequent disruption of plasmatocyte adhesion. Injection of double stranded integrin-beta1 RNA into larvae resulted in decreased integrin beta1 expression in plasmatocytes and significantly suppressed encapsulation. These results indicate that activation of ligand-binding by the hemocyte-specific integrin plays a key role in stimulating plasmatocyte adhesion leading to encapsulation.

Amino Acid Sequence↗
PubMed1997

Characterization of the binding of recombinant mouse sperm fertilin beta subunit to mouse eggs: evidence for adhesive activity via an egg beta1 integrin-mediated interaction.

The sperm protein fertilin (also known as PH-30) is a candidate for mediating the interactions between sperm and egg plasma membranes. Fertilin is a heterodimer. The beta subunit, which has a region with homology to the family of integrin ligands known as disintegrins, has been hypothesized to be involved in the binding of sperm to the egg surface. To investigate this hypothesis and determine what role fertilin beta plays in fertilization, we have expressed the putative extracellular domain of mouse fertilin beta in bacteria as a fusion protein with maltose-binding protein (hereafter referred to as recombinant fertilin beta-EC) and used two assays to characterize its binding to mouse eggs. Immunocytochemistry was used to examine the localization of recombinant fertilin beta-EC binding. A luminometric assay was also developed to quantify levels of binding of recombinant fertilin beta-EC to single eggs. We find that recombinant fertilin beta-EC binds to the region of the plasma membrane of the egg to which sperm bind, thus providing the first direct evidence that fertilin beta has adhesive properties. Peptides corresponding to the disintegrin domain of fertilin beta reduce its binding to eggs, suggesting that this domain is at least partially involved in the recognition of fertilin beta by binding sites on the egg. Treatment of zona pellucida-free eggs with chymotrypsin reduces the ability of the eggs to support the binding of recombinant fertilin beta-EC, implicating an egg surface protein as a binding site for recombinant fertilin beta-EC. Binding of recombinant fertilin beta-EC to eggs is also reduced in the absence of divalent cations and is supported by 2.0 mM Ca2+, Mg2+, or Mn2+. Furthermore, eggs incubated in recombinant fertilin beta-EC prior to in vitro fertilization show reduced levels of sperm binding. Finally, we have examined the possible role of integrins on eggs as receptors for fertilin beta, since an anti-alpha6 integrin subunit monoclonal antibody, GoH3, has been shown to inhibit sperm binding (E. A. C. Almeida et al. (1995) Cell 81, 1095-1104). We find that: (a) an increased amount of GoH3 epitope on the egg surface does not correlate with an increased ability of the eggs to bind sperm or recombinant fertilin beta-EC; (b) the GoH3 antibody has virtually no inhibitory effect on recombinant fertilin beta-EC binding; and (c) recombinant fertilin beta-EC binding is reduced in the presence of anti-beta1 integrin antibodies. These results suggest that a beta1-containing integrin participates in the binding of recombinant fertilin beta-EC to mouse eggs.

ADAM Proteins↗
PubMed1999

Signal transduction-mediated adherence and entry of Helicobacter pylori into cultured cells.

BACKGROUND & AIMS: An ability to invade host cells could be a means for Helicobacter pylori to achieve resistance to antibiotic therapy. The aim of this study was to investigate the mechanisms involved in adherence and entry of H. pylori into cultured cells. METHODS: Coinfection with Yersinia expressing mutant or wild-type YopH tyrosine phosphatase was used. Genistein and cytochalasin D were used as inhibitors of adherence and entry; entry was monitored by a gentamicin-protection assay. Target cells were AGS cells and a beta1-integrin-deficient cell line with its corresponding beta1-integrin-expressing transfectant. RESULTS: H. pylori induced phosphorylation of 125-130-kilodalton proteins, similar in size to the target proteins of Yersinia YopH. Adherence of H. pylori was inhibited by Yersinia organisms expressing enzymatically active YopH but not by inactive YopH. Adherence and entry of H. pylori was considerably higher with beta1-integrin-transfected cells than with beta1-integrin-deficient cells. Antibodies directed against alpha5- and beta1-integrin chains reduced adherence to the alpha5beta1-integrin-expressing gastric cell line AGS. Entry was inhibited by both cytochalasin D and genistein. Entry, but not adherence, was higher for 2 type I strains than for a type II isolate. CONCLUSIONS: Invasion of gastric epithelium via an integrin-mediated pathway could contribute to the ability of H. pylori to establish persistent infection.

Bacterial Adhesion↗