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At least 757 records · Page 42Linked to original sources
PubMed1995

Differential effects of monoclonal antibody blockade of adhesion molecules on in vivo susceptibility to soft tissue infection.

Leukocyte adherence to endothelial cells has been implicated in the pathogenesis of microvascular injury as well as in host defense against various infectious microorganisms. Administration of monoclonal antibodies directed against the beta chain of the leukocyte integrins inhibits leukocyte-endothelial-cell adherence and has been reported to modulate ischemia-reperfusion and inflammatory injury. However, such inhibition of adhesion molecule function adversely affects resistance to infection. The following studies were carried out to determine whether monoclonal antibodies to other adhesion molecules, including L-selectin (CD62L), and CD11a (the alpha chain of LFA-1), also increase susceptibility to infection. New Zealand White rabbits were shaved and given subcutaneous injections on their dorsa with 10(9) CFU of Staphylococcus aureus ATCC 25923 at two sites and with 10(8) CFU at two sites. A second set of rabbits were given subcutaneous injections with 10(8) CFU of P. aeruginosa ATCC 27853 at two sites and with 10(7) CFUs at two sites. The animals were monitored for 1 week. There were three blinded experimental groups: controls given saline and two groups given blocking monoclonal antibodies to either L-selectin (Dreg-200) or CD11a (R7.1). In contrast to monoclonal antibodies to CD18, none of the monoclonal antibodies significantly increased the risk of abscess formation by S. aureus, although inhibition of CD11a increased the rate of abscess formation by P. aeruginosa.

Abscess↗
PubMed2006

GA-binding protein and p300 are essential components of a retinoic acid-induced enhanceosome in myeloid cells.

Expression of CD18, the beta chain of the leukocyte integrins, is transcriptionally regulated by retinoic acid (RA) in myeloid cells. Full RA responsiveness of the CD18 gene requires its proximal promoter, which lacks a retinoic acid response element (RARE). Rather, RA responsiveness of the CD18 proximal promoter requires ets sites that are bound by GA-binding protein (GABP). The transcriptional coactivator, p300, further increases CD18 RA responsiveness. We demonstrate that GABPalpha, the ets DNA-binding subunit of GABP, physically interacts with p300 in myeloid cells. This interaction involves the GABPalpha pointed domain (PNT) and identifies p300 as the first known interaction partner of GABPalpha PNT. Expression of the PNT domain, alone, disrupts the GABPalpha-p300 interaction and decreases the RA responsiveness of the CD18 proximal promoter. Chromatin immunoprecipitation and chromosome conformation capture demonstrate that, in the presence of RA, GABPalpha and p300 at the proximal promoter recruit retinoic acid receptor/retinoid X receptor from a distal RARE to form an enhanceosome. A dominant negative p300 construct disrupts enhanceosome formation and reduces the RA responsiveness of CD18. Thus, proteins on the CD18 proximal promoter recruit the distal RARE in the presence of RA. This is the first description of an RA-induced enhanceosome and demonstrates that GABP and p300 are essential components of CD18 RA responsiveness in myeloid cells.

Binding Sites↗
PubMed2002

Role of endothelial MCP-1 in monocyte adhesion to inflamed human endothelium under physiological flow.

Monocyte chemoattractant protein-1 (MCP-1) is an essential chemokine involved in monocyte traffic across endo- and epithelial barriers both in vitro and in vivo. However, the contribution of endothelial MCP-1 signaling via its CCR2 receptor in monocyte adhesion to inflamed endothelium under flow is incompletely understood. A sensitive flow chamber assay was used to assess monocyte adhesion to TNF-alpha-activated primary human pulmonary artery endothelial cells (HPAEC) during physiological shear stress. Monocyte adhesion was markedly reduced ( approximately 45%) when HPAEC-derived MCP-1 was either neutralized with anti-MCP-1 mAb or inhibited by translational arrest of MCP-1 mRNA transcripts with MCP-1 antisense oligomers. Corresponding efficacy was observed for blockade of monocyte CCR2 receptor function by anti-CCR2 mAb or MCP-1 antagonists (9-76 analog). The impact of endothelial MCP-1 on monocyte-HPAEC adhesion occurred via beta(2)-integrin but not via beta(1)-integrin adhesion pathways. In this line, pretreatment of monocytes with MCP-1 but not RANTES provoked a rapid and transient neoepitope 24 expression on beta(2)-integrin alpha-chains, as analyzed by increased reporter mAb24 binding. Collectively, our data show an important cross talk of endothelial MCP-1 with monocyte CCR2 effecting monocyte firm adhesion to inflamed HPAEC under physiological flow conditions.

Antibodies, Monoclonal↗
PubMed2001

Autoantibodies to alpha(IIb)beta(3) in patients with chronic immune thrombocytopenic purpura bind primarily to epitopes on alpha(IIb).

Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disease caused by platelet destruction resulting from autoantibodies against platelet surface proteins, particularly platelet glycoprotein IIb/IIIa (alpha(IIb)beta(3)). To localize the auto-epitopes on platelet alpha(IIb)beta(3), the binding of autoantibodies to Chinese hamster ovary (CHO) cells expressing either alpha(IIb)beta(3) or alpha(v)beta(3) was studied. Thirteen of 14 ITP autoantibodies bound only to CHO cells expressing alpha(IIb)beta(3). Because these 2 integrins have the same beta chain (beta(3)), these results show that most epitopes in chronic ITP are dependent on the presence of glycoprotein alpha(IIb.) (Blood. 2001;97:2171-2172)

Adult↗
PubMed1992

Three monoclonal antibodies against human LFA-1 alpha and beta chains with different biological activities.

Three murine monoclonal antibodies (MAbs) directed against human lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18), designated as MAY.017, MAY.035, and MAY. 044, were newly generated. The hybridomas were screened for their ability to inhibit a phorbol ester-stimulated aggregation of Epstein-Barr virus-transformed B-lymphoblastoid cell line (B-LCL). The MAbs bound to peripheral blood leukocytes, T cell lines, B cell lines, and some of myeloid/monocytic lines, but not to B-LCL derived from a patient with leukocyte adhesion deficiency. MAY.035 immunoprecipitated a complex of proteins with molecular masses of 155 kDa and 95 kDa, while MAY.017 and MAY.044 did a complex of 130 kDa, 155 kDa and 95 kDa proteins. MAY.035 was shown as to recognize the alpha chain of LFA-1 (CD11a), and both MAY.017 and MAY.044 the beta chain of the beta 2 integrin family (CD18). All the three MAbs inhibited lymphocyte proliferative responses to mitogens or alloantigens. MAY.017 blocked cytolytic activity mediated by natural killer cells.

Adult↗
PubMed1992

Cloning and analysis of the CD18 promoter.

CD18, the common beta chain of the leukocyte integrin adhesion proteins, is expressed exclusively by myeloid cells and lymphocytes. During myeloid differentiation, the increase in CD18 cell surface expression is paralleled by increased CD18 messenger RNA levels. Nuclear run-on studies show that CD18 expression is transcriptionally regulated during 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced HL-60 monocytic differentiation. The CD18 transcriptional start site was defined by primer extension and RNAse protection. The gene encoding CD18 was cloned and a fragment that overlaps the transcriptional start site was isolated. DNA sequence analysis of this promoter fragment identified potential AP-1 elements that may mediate the TPA transcriptional response. The CD18 promoter also contains a putative binding site for PU.1, a leukocyte-specific transcription factor. DNA elements resembling those found in other myeloid and integrin promoters were identified. The CD18 promoter fragment was linked to the luciferase reporter gene, electroporated into the U937 monocytic cell line, and its expression increased after exposure to TPA. Thus, CD18 may serve as a model for identifying the cis elements and trans-acting factors that regulate gene expression during myeloid differentiation.

Antigens, CD↗
PubMed1993

Human osteoclast-like cells recognize laminin via an RGD independent mechanism.

Interactions between cells from human giant cell tumors of bone and the extracellular matrix protein laminin were studied. Cells were capable of recognizing this substratum via a RGD-independent mechanism. Recognition induces adhesion and spreading onto laminin. This protein triggered the release of cellular FN which in turn enhanced recruitment of the beta 1 chain-containing integrin receptor.

Amino Acid Sequence↗
PubMed1995

Characterization of human pancreatic adenocarcinoma cell line with high metastatic potential in SCID mice.

The CD44 molecule and CD44 isoforms are expressed on some malignant tumours and it has been suggested that their expression may correlate with tumour spread. Human pancreatic carcinoma cell line (HPC-4) expressing CD44 was established from a patient with adenocarcinoma of pancreas. This line showed a rapid growth in vitro, several chromosome abnormalities and surface expression of some adhesion molecules (ICAM-1, LFA-3, beta 1-chain of VLA integrins, VNR). Xenotransplanted HPC-4 cells were able to grow rapidly in SCID mice as subcutaneous tumour, leading to 100% mortality within 3-5 weeks when 1 x 10(5)-1 x 10(7) cells were inoculated. Spontaneous metastases in the liver, lung, spleen and kidney of SCID mice were observed. Interestingly enough, HPC-4 cells in vivo and ex vivo also expressed HLA-DR molecules, but these were rapidly lost upon culture in vitro. It is suggested that the appearance of HLA-DR may be the result of interaction of the tumour with a local environment of the host, while CD44 expression may explain the rapid growth and occurrence of distant metastases in SCID mice. The ability of HPC-4 cells to form spontaneous metastases in SCID mice may prove to be a potentially interesting model of human carcinoma for testing new treatment modalities.

Adenocarcinoma↗
PubMed1995

Phenotypic analysis of the glomerular and periglomerular mononuclear cell infiltrates in the Thy 1.1 model of glomerulonephritis.

BACKGROUND: The phenotype of macrophages invading the mesangium and periglomerular region has not been described in experimental mesangial proliferative glomerulonephritis, although it has implications for the mechanism of entry of these cells into these locations and their function once there. We have, therefore, determined the phenotype of the periglomerular leukocytic infiltrate in the Thy 1.1 model of mesangial proliferative glomerulonephritis and compared it with that of cells invading the mesangium. EXPERIMENTAL DESIGN: The Thy 1.1 model was induced in Lewis rats, and sections were taken at 1 hour and at 1, 4, 9, 30, and 90 days postinduction. Immunohistochemistry was performed using monoclonal antibodies against macrophage markers (ED-1, CD4, RT1-B, and ED-2), chains of the beta 2 integrins (CD18, CD11a, and CD11b), T and B cell markers (CD8, T cell receptor, interleukin-2 receptor, and MRC OX33), and markers of mesangial cell proliferation (proliferating cell nuclear antigen, alpha-smooth muscle actin). Sections were compared with those obtained from control animals. RESULTS: In untreated rats, a striking resident periglomerular macrophage population (phenotype ED-1-ve ED-2-ve CD4+ve RT1-B+ve CD18+ve CD11a+ve CD11b+ve) was found, confirming a previous report. From 24 hours postinduction, this resident macrophage population was supplemented by a population whose predominant phenotype (ED-1+ve ED-2-ve CD4+ve RT1-B+ve CD18+ve CD11a+ve CD11b+ve) was identical to that of macrophages infiltrating the mesangium. Both infiltrates peaked at 4 days and returned to base-line levels by 1 to 3 months. There was no significant lymphocyte infiltrate within the glomerulus and only a minimal periglomerular T cell infiltrate. CONCLUSIONS: These data show, first, that disease limited to the mesangium can lead directly to periglomerular macrophage infiltration. Second, the presence of CR3 (i.e., CD11b and CD18) and LFA-1 (i.e., CD11a and CD18) on the macrophage infiltrate indicates that both ligands are important for cells to enter the mesangium and periglomerular areas. Third, the marked phenotypic and temporal similarities between the mesangial and periglomerular macrophage infiltrates suggests that a common factor(s) is involved in their pathogenesis. Finally, expression of RT1-B (Ia) but not ED-2 is reported to be typical of interstitial dendritic cells rather than tissue macrophages, suggesting a unique function for the glomerular and periglomerular macrophage infiltrate in this model.

Animals↗
PubMed1994

Adherence of neutrophils induces release of soluble tumor necrosis factor receptor forms.

TNF is a potent activator of neutrophil granulocytes which acts via two cell surface receptors: the p55-TNF receptor (TNF-R55) and the p75-TNF receptor (TNF-R75). The extracellular region of the receptors can be released by proteolytic cleavage and form soluble TNF-binding proteins, TNF-R55-BP and TNF-R75-BP, respectively. The phorbol ester PMA, the chemotactic peptide FMLP, and TNF were all found to induce release of TNF-R55-BP and TNF-R75-BP from neutrophils in suspension in a time- and dose-dependent manner as measured by ELISA. Exposure of neutrophils to 10 ng/ml of PMA for 60 min resulted in release of 900 pg of TNF-R55-BP and 350 pg of TNF-R75-BP per 5 million cells, corresponding to approximately 4800 receptors per cell. In addition, adherence by itself of neutrophils to fibrinogen-coated culture plates and other surfaces resulted in a release of TNF-R55-BP of the same magnitude as seen in response of neutrophils in suspension to 1 nM TNF, whereas the release of TNF-R75-BP was less pronounced. The protein kinase C inhibitors staurosporin and calphostin C inhibited both the TNF-, PMA-, and adherence-induced release of soluble forms of TNFRs. Ab to the common beta-chain of the leukocyte integrins (CD18) did not affect adherence-induced TNF-R55-BP release, indicating that non-integrin-dependent mechanisms are involved in receptor cleavage. However, cross-linking of anti-CD18 Ab (IB4) with a Fab2 fragment resulted in a decrease of specific binding of 125I-TNF to neutrophils indicating that the leukocyte integrins can modulate TNFR expression on neutrophils. Thus, adherence to a biological surface, without additional stimuli, induces release of soluble TNFR form from neutrophils. TNFR expression can be modulated by protein kinase C as well as both leukocyte integrins and non-integrin-dependent adherence mechanisms.

Antigens, CD↗
PubMed1996

Sequence 274-368 in the beta 3-subunit of the integrin alpha IIb beta 3 provides a ligand recognition and binding domain for the gamma-chain of fibrinogen that is independent of platelet activation.

Several bacterial-expressed recombinant fragments encompassing the extracellular part of the beta 3 subunit of the integrin alpha IIb beta 3 were shown to recognize and bind soluble and immobilized forms of fibrinogen. Two of them, designated as rIII-11 (beta 3 274-368) and rIII-13 (beta 3 274-403), did not contain the established RGD-ligand binding sequence. In fact, they interacted, in a Ca(2+)-independent manner, with the C-terminal part of the fibrinogen gamma chain. Both beta 3 fragments blocked the participation of fibrinogen in the induction of platelet aggregation induced by adenosine diphosphate. Fragment rIII-13 was recognized by the anti-beta 3 monoclonal antibody B2A. This antibody, which possesses an epitope exposed on both resting and activated platelets, inhibited fibrinogen binding as well as platelet adhesion and aggregation. In conclusion, the results demonstrated that the 274-368 sequence of the beta 3 subunit of integrin alpha IIb beta 3 constitutes a fibrinogen ligand binding domain, distinct from the RGD-binding site, that is required for both platelet adhesion and aggregation.

Adenosine Diphosphate↗
PubMed2004

The LIM-only proteins FHL2 and FHL3 interact with alpha- and beta-subunits of the muscle alpha7beta1 integrin receptor.

FHL1, FHL2, and FHL3 are members of the four and one-half LIM domain protein subclass that are expressed in striated muscles. Here we show that FHL2 and FHL3 are novel alpha(7)beta(1) integrin-interacting proteins. They bind both the alpha- and the beta-subunit as well as different splice isoforms. The minimal binding sites for FHL2 and FHL3 on beta(1A)-chain overlap, whereas on alpha(7A) and alpha(7B) subunits they are situated adjacent. Determining the binding sites for integrins on FHL2 or FHL3 revealed that the suprastructure of the whole molecule is important for these associations, rather than any single LIM domain. Immunofluorescence studies with cells expressing full-length FHL proteins or their deletion mutants showed that FHL2 and FHL3 but not FHL1 colocalize with integrins at cell adhesion sites. Further, their recruitment to the membrane results from binding to either the alpha- or the beta-chain of the integrin receptor. The association of FHL2 or FHL3 with integrin receptors neither influences attachment of cells to different substrates nor changes their migration capacity. However, in cardiac and skeletal muscles, FHL2 and FHL3, respectively, are colocalized with alpha(7)beta(1) integrin receptor at the periphery of Z-discs, suggesting a role in mechanical stabilization of muscle cells.

Actins↗
PubMed1990

Interaction of integrins alpha v beta 3 and glycoprotein IIb-IIIa with fibrinogen. Differential peptide recognition accounts for distinct binding sites.

Glycoprotein (GP) IIb-IIIa is the major fibrinogen receptor on platelets and participates in platelet aggregation at the site of a wound. Integrin alpha v beta 3, which contains an identical beta-subunit, is expressed on endothelial cells and also serves as a fibrinogen receptor. Here, we demonstrate by several criteria that purified GPIIb-IIIa and integrin alpha v beta 3 bind to distinct sites on fibrinogen. First, a plasmin-generated fragment of fibrinogen lacking the RGD sequence at residues 572-574 retained the ability to bind GPIIb-IIIa, but failed to bind integrin alpha v beta 3. Second, a monoclonal antibody which exclusively recognizes the RGD sequence at fibrinogen A alpha chain residues 572-574 abolished interaction between integrin alpha v beta 3 and fibrinogen, but had only a minimal effect on fibrinogen binding to GPIIb-IIIa. Finally, we show that the difference in recognition of sites on fibrinogen by these two integrins is probably a consequence of their remarkably different ligand binding properties. Peptides corresponding to fibrinogen gamma chain residues 400-411 effectively blocked RGD sequence and fibrinogen binding by GPIIb-IIIa, but had no effect on the ability of integrin alpha v beta 3 to bind these ligands. We also show that integrin alpha v beta 3 has a higher affinity than GPIIb-IIIa for a synthetic hexapeptide containing the RGD sequence. In fact, this RGD-containing peptide was 150-fold more effective at blocking fibrinogen binding to integrin alpha v beta 3 than to GPIIb-IIIa. Collectively, our results demonstrate that integrins alpha v beta 3 and GPIIb-IIIa display qualitative and quantitative differences in their ligand binding properties, as is evident by their ability to interact with synthetic peptides. The ultimate result of these differences is the recognition of distinct sites on fibrinogen by the two integrins. These observations may have relevance in the processes of hemostasis and wound healing.

Amino Acid Sequence↗
PubMed1990

Identification of a novel integrin beta subunit expressed on cultured monocytes (macrophages). Evidence that one alpha subunit can associate with multiple beta subunits.

The vitronectin receptor (VnR) is one member of a subset of cell adhesion receptors within the integrin supergene family which shares the beta 3 subunit (IIIa). We show here that the VnR is absent from the surface of monocytes freshly isolated from blood but is expressed on these cells after a period of in vitro culture. Such cultured monocytes (macrophages) from a patient with type I Glanzmann's thrombasthenia, however, failed to express the VnR. Instead, immunoprecipitation with a monoclonal antibody directed to the VnR alpha chain (alpha v) revealed a novel integrin comprising alpha v associated noncovalently with a 100-kDa beta subunit (beta 3b), immunologically unrelated to the VnR beta subunit (beta 3a). This same novel integrin complex was also identified on 10-day-old macrophages from healthy donors, but on these cells, the beta 3b subunit was co-expressed with the classical VnR complex of alpha v beta 3a. The novel beta 3b subunit was not identified by monoclonal or polyclonal antibodies to IIIa (beta 3a) nor by a monoclonal antibody to the classical VnR complex. The beta 3b subunit could be distinguished from beta 3a by its relatively greater migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis after reduction, by its distinct isoelectric point upon two-dimensional gel electrophoresis, and by one-dimensional peptide mapping. Neither platelets nor B lymphoblasts from this patient with Glanzmann's thrombasthenia expressed any VnR on their surface, whereas control cells from a normal donor expressed the classical VnR but not the beta 3b subunit. The two beta chains, and hence also the combined receptor complexes, appeared to be differentially regulated. These findings provide the first example of an integrin alpha chain complexed with more than a single beta chain in the same cell. Furthermore, the differential regulation of expression of the different beta subunits that associate with the VnR alpha chain on cultured monocytes suggests a role for the novel receptor complex during monocyte/macrophage differentiation.

Adult↗
PubMed1999

alpha6beta1 integrin expression in hepatocarcinoma cells: regulation and role in cell adhesion and migration.

Liver carcinogenesis is associated with striking changes in the integrin repertoire of hepatocytes, including the overexpression of the laminin and collagen receptors alpha1beta1 and the de novo induction of the laminin receptor alpha6beta1. Our aim was to analyze the role of pro-inflammatory cytokines, interferons and fibrogenic cytokines TGF-beta and FGF2 in the regulation of the expression of beta1 integrins by neoplastic hepatocytes. The 2 human hepatocellular cell lines HepG2 and Hep3B were used as models. Integrin expression was assessed by qualitative methods (immunocytochemistry, Western blotting) and semi-quantitative techniques (FACS, cellular ELISA), before and after stimulation by TNFalpha, IL1-beta, TGF-beta, FGF2, interferon gamma and interferon alpha-2b. HepG2 and Hep3B constitutively expressed alpha1, alpha2, alpha6 and beta1 chains. A 24 to 48-hr stimulation with pro-inflammatory cytokines, TGF-beta and FGF2 induced a significant increase in the concentrations of all integrin chains. The maximum induction was registered for beta1 chain, which presented increases amounting up to 3, 4 and 7 times the control values in the presence of, respectively, TNF alpha/IL1-beta, TGF-beta and FGF2. Interferons had no direct effect on integrin expression and partially antagonized the effects of TNF alpha and TGF-beta. The increased concentrations of integrin chains were associated with an increased membrane expression of the corresponding dimers and with an increased adhesion of stimulated hepatocytes to laminin, which was antagonized by neutralizing anti-beta1 and anti-alpha6 antibodies. Finally, anti-alpha6 antibody inhibited the migration of HepG2 and Hep3B cells in reconstituted basement membrane. Our results suggest that the stimulation of alpha6beta1 integrin expression in hepatocarcinoma cells is essential for cell adhesion and migration.

Carcinoma, Hepatocellular↗
PubMed1994

Reciprocal expression of laminin A-chain isoforms along the crypt-villus axis in the human small intestine.

BACKGROUND/AIMS: Intestinal epithelial cell proliferation, migration, and differentiation are susceptible to various influences along the crypt-villus axis including compositional changes in the basement membrane and differential expression of receptors for these components. However, laminin has been consistently detected at the epithelial basement membrane without significant variation in relation to the crypt-villus functional unit. The aim of this study was to examine the distribution of individual laminin chains. METHODS: The patterns of distribution of laminin A, M (an A-chain variant), B1, and B2 chains as well as the integrins alpha 6 beta 1 and alpha 6 beta 4, two laminin receptors, were determined by indirect immunofluorescence in the adult human small intestine. RESULTS: Markedly distinct patterns of laminin chain expression were observed along the crypt-villus axis. The A chain was found predominantly associated with the differentiated epithelial cells on the villus whereas the M chain was restricted to the basement membrane of crypts. However, both B1 and B2 chains were detected all along the intestinal basement membrane. Furthermore, alpha 6 beta 1 and alpha 6 beta 4 integrins were found to be expressed by all enterocytes. CONCLUSIONS: These observations show a reciprocal expression of laminin isoforms along the crypt-villus axis and support the concept that the intestinal epithelial basement membrane is subjected to intricate compositional changes.

Adult↗
PubMed2001

Laminin synthesis and the adhesion characteristics of immortalized human corneal epithelial cells to laminin isoforms.

We have studied the synthesis of laminins (Ln) and determined the specific integrins mediating the adhesion of immortalized human corneal epithelial cells to mouse Ln-1, and human Lns-5 and -10. Immunofluorescence microscopy of the cells demonstrated integrin alpha(2), alpha(3), alpha(6), beta(1)and beta(4)subunits, integrins alpha(6)and beta(4)being found in a typical 'leopard-skin' like manner. Immunoprecipitation studies showed that the cells produced alpha 3, beta 3 and gamma 2 chains of Ln-5, but not Lns-1 or -10. In culture Ln-5 was found as small plaques beneath the adhering cells within 1 hr, while in 4 hr widely spread Ln-5 plaques were observed in colocalization with beta(4)integrin subunit. By using a quantitative cell adhesion assay and function-blocking monoclonal antibodies we showed that integrin beta(1)subunit plays a role in mediating corneal epithelial cell adhesion to mouse Ln-1. However, none of the available function-blocking antibodies to integrin alpha-subunits inhibited the adhesion. Integrin alpha(3)beta(1)complex mediated the adhesion of corneal epithelial cells to human Lns-5 and -10. Integrin complex alpha(3)beta(1), as well as laminin alpha(3)chain, was also shown to mediate cell adhesion to newly produced endogenous Ln-5. The present results show that integrin alpha(3)beta(1)complex mediates the adhesion of corneal epithelial cells to Lns-5 and -10, while a yet unknown integrin alpha subunit appears to play a role in the adhesion to Ln-1. The results also show that among corneal basement membrane laminins, Ln-5 is synthetized by epithelial cells while Ln-10 may be a product of keratocytes.

Animals↗
PubMed2003

Roles of luteinizing hormone/chorionic gonadotropin receptor in anchorage-dependent and -independent growth in human ovarian surface epithelial cell lines.

Epithelial ovarian carcinomas are thought to arise from cells of ovarian surface epithelium (OSE) covering the free surface of the human ovary. Two immortalized human cell lines, OSE2a (non-tumorigenic) and OSE2b-2 (tumorigenic), were previously established from normal OSE cells of a reproductive-age patient. In the present study, we found that expression of luteinizing hormone (LH)/chorionic gonadotropin (CG) receptor (LH/CGR) is present in OSE2a cells and absent in OSE2b-2 cells. In OSE2a cells, a low concentration (10(3) mIU/ml) of CG enhanced anchorage-dependent growth via up-regulation of insulin-like growth factor-1 (IGF1), whereas a high concentration (10(5) mIU/ml) of CG induced anchorage-independent growth and down-regulation of IGF1 expression. To investigate involvement of other genes in LH/CGR-related tumorigenicity, we compared cDNA expression arrays of OSE2a and OSE2b-2 cells, and found that the following genes had lower expression in OSE2b-2 than in OSE2a: integrin beta 1, intercellular adhesion molecule-1 (ICAM1), and Waf1/Cip1. Subsequent semiquantitative reverse transcription polymerase chain reaction using OSE2a cells showed that expression of integrin beta 1 was down-regulated by a high concentration (10(5) mIU/ml) of CG. These results suggest that LH/CGR affects anchorage-dependent and -independent growth by mediating up- and down-regulation of IGF1 and integrin beta 1. Repetitive and excessive activation of LH/CGR may cause genetic alteration of its signal transduction pathway, resulting in stimulation of growth of OSE cells, initiation of ovarian carcinogenesis, and cancer progression.

Cell Adhesion↗