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At least 685 records · Page 38Linked to original sources
PubMed2000

Identification of amino acid sequences in fibrinogen gamma -chain and tenascin C C-terminal domains critical for binding to integrin alpha vbeta 3.

Integrin alpha(v)beta(3) recognizes fibrinogen gamma and alpha(E) chain C-terminal domains (gammaC and alpha(E)C) but does not require the gammaC dodecapeptide sequence HHLGGAKQAGDV(400-411) for binding to gammaC. We have localized the alpha(v)beta(3) binding sites in gammaC using gammaC-derived synthetic peptides. We found that two peptides GWTVFQKRLDGSV(190-202) and GVYYQGGTYSKAS(346-358) block the alpha(v)beta(3) binding to gammaC or alpha(E)C, block the alpha(v)beta(3)-mediated clot retraction, and induce the ligand-induced binding site 2 (LIBS2) epitope in alpha(v)beta(3). Neither peptide affects fibrinogen binding to alpha(IIb)beta(3). Scrambled or inverted peptides were not effective. These results suggest that the two gammaC-derived peptides directly interact with alpha(v)beta(3) and specifically block alpha(v)beta(3)-gammaC or alpha(E)C interaction. The two sequences are located next to each other in the gammaC crystal structure, although they are separate in the primary structure. Asp-199, Ser-201, Gln-350, Thr-353, Lys-356, Ala-357, and Ser-358 residues are exposed to the surface. This suggests that the two sequences are part of alpha(v)beta(3) binding sites in fibrinogen gammaC domain. We also found that tenascin C C-terminal fibrinogen-like domain specifically binds to alpha(v)beta(3). Notably, a peptide WYRNCHRVNLMGRYGDNNHSQGVNWFHWKG from this domain that includes the sequence corresponding to gammaC GVYYQGGTYSKAS(346-358) specifically binds to alpha(v)beta(3), suggesting that fibrinogen and tenascin C C-terminal domains interact with alpha(v)beta(3) in a similar manner.

Amino Acid Sequence↗
PubMed2003

Integrin pattern in human endometrium--new diagnostic tool in pelvic endometriosis?

OBJECTIVES: The only possibility to diagnose peritoneal endometriosis is laparoscopy or laparotomy with tissue sampling for histology. Women with impalpable endometriosis not visible on ultrasound suffering from infertility or teenagers with pelvic pain, where endometriosis may also be expected, would greatly benefit from an inoperative diagnostic method. A sure and comfortable method of assessing the effectiveness of endometriosis treatment does not exist. The aim of the study was description of the alpha 3 beta 1, alpha 4 beta 1 integrins and beta 1 chain expression in endometrial biopsies in women suffering from endometriosis. MATERIAL AND METHODS: Laparoscopy and hysteroscopy was performed in 32 patients because of infertility (n = 23) and/or pelvic pain (n = 11). For histochemical stainings of endometrial biopsy primary and secondary mouse antibodies to human integrins alpha 3 beta 1, alpha 4 beta 1 and beta 1 chain were used (DAKO). RESULTS: In 17 women peritoneal endometriosis was diagnosed by biopsy at the time of laparoscopy. An alpha 3 beta 1 integrin was more common in the glandular epithelium of women with endometriosis and beta 1 subunit was less frequently observed in the stroma of the endometriosis group than in women without endometriosis. The differences were statistically significant. CONCLUSION: The selected integrins do not yet allow finding a pattern characteristic for endometriosis.

Adult↗
PubMed1992

Expression of adhesion proteins involved in cell-cell and cell-matrix interactions in the skin of patients with progressive systemic sclerosis.

BACKGROUND: Lymphocytic infiltration and activation of connective tissue metabolism in the early phase of progressive systemic sclerosis (PSS, scleroderma) may be critically influenced by cellular adhesion molecules (CAMs), which mediate cell-cell and cell-extracellular matrix interactions. OBJECTIVE: The tissue distribution might demonstrate a pathogenetic role of these adhesion molecules in early edematous and chronic fibrotic scleroderma. METHODS: We investigated by immunohistochemical techniques the in situ expression and distribution of beta 1 and beta 2 integrins, selectins, and CAMs of the immunoglobulin superfamily in patients with scleroderma. RESULTS: In the early disease stage a moderate percentage of perivascular CD3+/CD4+/TCR alpha/beta + lymphocytes showed expression of the alpha 3, alpha 5, and beta 1 chains and, to a lesser degree, of the alpha 1, alpha 2, alpha 4 and alpha 6 subunits. In contrast to chronic PSS, LFA-1 alpha, LFA-1 beta and ICAM-1 expression on mononuclear infiltrating cells was seen more frequently in acute scleroderma. Different percentages of fibroblasts expressed alpha 1-, alpha 3-, alpha 5- and beta 1-integrin chains. In acute PSS ICAM-1 was expressed especially by fibroblasts located around perivascular inflammatory infiltrates as well as by endothelial cells (ECs). A few ECs expressed alpha 2 beta 1 integrins. CONCLUSION: Our observations suggest that CAMs are intimately involved in early pathogenetic events in scleroderma, mediating cellular interactions between lymphocytes, ECs, and fibroblasts, as well as homing and tissue targeting of mononuclear infiltrating cells.

Acute Disease↗
PubMed2003

Control of thrombus embolization and fibronectin internalization by integrin alpha IIb beta 3 engagement of the fibrinogen gamma chain.

Fibrin(ogen) deficiency (Fg-/-) was shown previously to be compatible with rapid thrombus growth within injured arterioles, but platelet fibronectin content was increased and newly formed thrombi were unstable. To further define the role of fibrin(ogen) in thrombus formation and stabilization, platelet biology was examined in mice expressing a form of fibrinogen that clots normally but lacks the gamma chain C-terminal binding site for alpha IIb beta 3 (Fg gamma Delta 5). Thrombus growth within the arterioles of Fg gamma Delta 5 mice appeared faster than in wild-type mice despite a far greater emboli formation. Unlike Fg-/- mice, the emboli were relatively small and released from the top of thrombi, rather than by fracture at the vessel wall. The fibronectin content in Fg gamma Delta 5 platelets was also dramatically increased through a beta 3 integrin-dependent mechanism. The following has been concluded: (1) Fibrin formation contributes to, but is not sufficient for, the stabilization of arterial thrombi. Platelet receptor engagement of the C-terminal of the Fg gamma chain contributes to the stable incorporation of platelets into thrombi. (2) Alternative ligands to fibrinogen can support efficient thrombus growth. (3) Fibrinogen is internalized through alpha IIb beta 3 engagement of the fibrinogen gamma chain element, and this interaction secondarily controls the fibronectin content of platelets.

Afibrinogenemia↗
PubMed1997

Identification of integrin-dependent and -independent cell adhesion domains in COOH-terminal globular region of laminin-5 alpha 3 chain.

Laminin-5 is an isoform of laminin that consists of alpha 3, beta 3, and gamma 2 chains and has potent cell adhesion- and cell migration-promoting activities. In this study, five subdomains in the COOH-terminal globular (G) domain of human laminin alpha 3 chain were individually expressed in Escherichia coli, and their biological activities were investigated. Recombinant G2, G4, and G5 domains promoted adhesion to plastic plates of HT1080 fibrosarcoma cells, A431 epidermoid carcinoma cells, and ECV304 vascular endothelial cells. For the cell adhesion activity, the G2 domain required a divalent cation and heat-sensitive conformation more strongly than G4 and G5. The cell adhesion to G2 but not G4 and G5 was effectively inhibited by an anti-integrin alpha 3 antibody. A cell adhesion sequence of 22 amino acids, alpha 3G2A, that was homologous to the integrin alpha 3 beta 1-binding sequence GD-6 of laminin alpha 1 chain was identified within the G2 structure. The cell adhesion to alpha 3G2A peptide was also inhibited by the anti-integrin alpha 3 antibody. The cell adhesion to G2, alpha 3G2A, G4, and G5 was strongly inhibited by heparin, but that to native laminin-5 was inhibited less effectively. Moreover, G5 potently stimulated chemotactic migration of rat liver epithelial cells in Boyden chambers, but G2 and G4 did not. These results indicate that the G domain of laminin alpha 3 contains multiple cell binding sites with different mechanisms and different functions. The G2 domain seems to recognize integrin alpha 3 beta 1, whereas G4 and G5 may interact with heparin-like molecules on cell surface.

Animals↗
PubMed1994

Integrin expression in squamous neoplasia of the cervix.

Epithelial cell-basement membrane interactions are important in maintaining tissue architecture and function, and the anatomical and functional relationships between epithelial cells and their basement membranes are clearly altered in malignancy. These interactions are thought to be largely mediated by the integrins, a family of heterodimeric transmembrane glycoproteins, each consisting of an alpha and a beta chain. Epithelial integrins mainly belong to the beta 1 (VLA) subfamily, which forms receptors for matrix macromolecules such as fibronectin, laminin, and collagen. There is evidence that integrin expression changes in some epithelial malignancies, possibly in relation to invasive potential. Integrin expression in cervical neoplasia was studied by immunohistochemical examination of prospectively collected colposcopic biopsies. Well-characterized monoclonal antibodies against beta 1-4, alpha 1-6, and alpha V integrins were used to examine normal, koilocytic, and dysplastic cervical squamous epithelium, and invasive squamous carcinoma. beta 1, beta 4, alpha 2, alpha 3, alpha 6, and alpha V were expressed by the basal layer of normal cervical squamous epithelium and by dysplastic cells in CIN (cervical intraepithelial neoplasia) 1 and 2, with none being lost and no new chains acquired. In CIN3, these integrins were either expressed throughout the ectocervical epithelium or restricted to the basal layer. In the latter cases, integrin expression was retained to a greater degree by dysplastic squamous epithelium within endocervical glands. These patterns could not be correlated with age or smear history in the cases examined. Patterns of integrin expression in neoplastic cervical epithelium therefore differ from those of normal cervical epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Clones of tumor cells derived from a single primary human lung tumor reveal different patterns of beta 1 integrin expression.

Previously we reported that over 75% of human non-small cell lung cancers overexpress the beta 1 integrin VLA-2 on their surface and show an increase in the mRNA encoding the alpha-2 chain of this integrin. These results suggested the possibility that the overproduction and overexpression of one or more of the beta 1 integrin may be involved in the pathogenesis of human lung tumors by modulating the invasive and/or metastatic potential of the tumor. We report here the generation and characterization of multiple clones of tumor cells derived from the primary culture of cells obtained from biopsy tissue of an aggressive human squamous cell lung tumor. We show that these tumor clones (or clonotypes) exhibit seven different yet stable phenotypes with respect to the expression of five members of the beta 1 integrin family. These results illustrate that a primary human lung tumor consists of multiple subpopulations of cells that while indistinguishable by ultrastructure are heterogeneous with respect to their beta 1 integrins. The availability of these distinct tumor clonotypes derived from a single tumor biopsy have made it possible to test the assumption that the beta 1 integrins play a role in tumor progression. The feasibility of this approach is demonstrated here by the intravenous inoculation of different human tumor clonotypes into severe combined immunodeficient (scid) mice. Our preliminary results with a pair of tumor clonotypes differing in VLA-1 and VLA-2 expression level reveal that the clonotype with high level of VLA-1 and VLA-2 displays a substantial increase in the experimental engraftment and metastasis of the human tumor cells in scid mice.

Animals↗
PubMed1999

PETA-3/CD151, a member of the transmembrane 4 superfamily, is localised to the plasma membrane and endocytic system of endothelial cells, associates with multiple integrins and modulates cell function.

The Transmembrane 4 Superfamily member, PETA-3/CD151, is ubiquitously expressed by endothelial cells in vivo. In cultured human umbilical vein endothelial cells PETA-3 is present on the plasma membrane and predominantly localises to regions of cell-cell contact. Additionally, this protein is abundant within an intracellular compartment which accounts for up to 66% of the total PETA-3 expressed. Intracellular PETA-3 showed colocalisation with transferrin receptor and CD63 suggesting an endosomal/lysosomal localisation which was supported by immuno-electronmicroscopy studies. Co-immunoprecipitation experiments investigating possible interactions of PETA-3 with other molecules demonstrated associations with several integrin chains including beta1, beta3, beta4, (alpha)2, (alpha)3, (alpha)5, (alpha)6 and provide the first report of Transmembrane 4 Superfamily association with the (alpha)6beta4 integrin. Using 2-colour confocal microscopy, we demonstrated similar localisation of PETA-3 and integrin chains within cytoplasmic vesicles and endothelial cell junctions. In order to assess the functional implications of PETA-3/integrin associations, the effect of anti-PETA-3 antibodies on endothelial function was examined. Anti-PETA-3 mAb inhibited endothelial cell migration and modulated in vitro angiogenesis, but had no detectable effect on neutrophil transendothelial migration. The broad range of integrin associations and the presence of PETA-3 with integrins both on the plasma membrane and within intracellular vesicles, suggests a primary role for PETA-3 in regulating integrin trafficking and/or function.

Antigens, CD↗
PubMed2006

Molecular cloning and characterization of cDNA encoding CD11b of cattle.

CD18, the common beta subunit of beta2-integrins, associates with four distinct alpha chains to give rise to four different beta2-integrins: CD11a/CD18 (LFA-1), CD11b/CD18 (Mac-1), CD11c/CD18 (CR4), and CD11d/CD18. Previously, we and others showed that CD18 of LFA-1 serves as a receptor for Mannheimia haemolytica leukotoxin (Lkt). Level of expression of Mac-1 is higher than that of LFA-1 and other beta2-integrins on polymorphonuclear leukocytes (PMNs), which constitute the leukocyte subset most susceptible to Lkt. Hence, it is likely that CD18 of Mac-1 also mediates Lkt-induced cytolysis. Co-expression of CD11b and CD18 of cattle on Lkt-resistant cells is necessary to irrefutably demonstrate the role of Mac-1 in Lkt-induced cytolysis. This approach is hindered by lack of availability of complete sequence of cattle CD11b. Therefore, in this study, we cloned and sequenced the full length cDNA encoding cattle CD11b. The 3459 bp cDNA of cattle CD11b encodes a polypeptide of 1152 amino acids. The deduced amino acid sequence of CD11b of cattle exhibits 75% identity to that of humans and chimpanzees, 74% identity to that of dogs, and 70% identity to that of mice and rats. Availability of cattle CD11b cDNA should facilitate the elucidation of Lkt-receptor interactions in cattle and other species.

Amino Acid Sequence↗
PubMed1996

Inherited mutations within the calcium-binding sites of the integrin alpha IIb subunit (platelet glycoprotein IIb). Effects of the amino acid side chain and the amino acid position on cation binding.

To examine the effects of naturally occurring inherited mutations on the ability of the integrin alpha-subunit, also termed glycoprotein IIb (GPIIb), to bind metal ions, we prepared small synthetic peptides that encompassed individual cation-binding domains, and recombinant GPIIb poly peptides that encompassed all four Ca(2+)-binding domains, and examined their interactions with divalent cations by means of Tb3+-luminescence spectroscopy. Replacement of the highly conserved Gly418 residue, located within the flanking region of the fourth Ca(2+)-binding domain of GPIIb, with a negatively charged Asp residue resulted in marked reduction in the ability to bind divalent cations. A variant form of GPIIb with a deletion of two amino acids at the -1 and X positions of the fourth Ca(2+)-binding domain of GPIIb also failed to bind metal ions in a normal manner. In contrast, a Glanzmann mutation at the -1 position of the first Ca(2+)-binding domain of GPIIb had no effect on divalent-cation-binding ability with either synthetic peptides or recombinant GPIIb polypeptides. These data support the hypothesis that the highly conserved Gly normally found 7-8 residues N-terminal to integrin metal-binding domains plays a critical role in the maintenance of the conformation or orientation of surrounding EF-hand structures so that they can effectively interact with and bind divalent cations. Furthermore, inherited mutations at or near the divalent-cation-binding domains of GPIIb do not necessarily exert their biochemical effects by disruption of cation binding, but can interfere with integrin biogenesis in a Ca(2+)-independent manner.

Amino Acid Sequence↗
PubMed2005

Identification of expressed genes in carp (Cyprinus carpio) head kidney cells after in vitro treatment with immunostimulants.

We analysed a total of 530 expressed genes from the head kidney cells of common carp (Cyprinus carpio) treated by immunostimulants. Sequences of the cDNA clones were compared with sequences in the GenBank database. Immune-related genes identified after in vitro stimulation of carp head kidney cells were: BPI/LBP, C-type lectins, fucolectins, CC-chemokine, CXC-chemokine, CD18, cyclophilin, FcgammaR, G-CSFR, HSP 70, Ig heavy and light chains, NITR, integrin beta2-alpha, Mx, interleukin-1beta, beta thymosin, lysozyme G & C, MHC class II associated invariant chain 1 and 2, granulin, CAAT binding protein and tumour necrosis factor-alpha induced protein. The expression of these immune-related genes may be important for estimating the efficacy of immunostimulants.

Adjuvants, Immunologic↗
PubMed2001

Ligation of CD11b and CD11c beta(2) integrins by antibodies or soluble CD23 induces macrophage inflammatory protein 1alpha (MIP-1alpha) and MIP-1beta production in primary human monocytes through a pathway dependent on nuclear factor-kappaB.

Chemokines and adhesion molecules such as integrins play a major part in the trafficking, extravasation, and recruitment of leukocytes to inflammatory sites. This study investigated the effects of beta(2) integrin engagement on chemokine production by freshly isolated human monocytes. We found that ligation of CD11b or CD11c but not CD11a alpha chains of beta(2) integrins by antibodies or soluble CD23 (sCD23) fusion proteins rapidly induced transcription and secretion of interleukin 8, macrophage inflammatory protein (MIP) 1alpha, and MIP-1beta. Because the promoters of these chemokine genes contain kappaB binding sites, we assessed the possible role of nuclear factor-kappaB (NF-kappaB) in controlling induction of the genes through beta(2) integrin engagement. Electrophoretic mobility shift assays showed that sCD23 or antibodies to CD11b or to CD11c up-regulated DNA-binding activity of NF-kappaB. Activation of NF-kappaB was accompanied by degradation of its cytosolic inhibitor IkappaB-alpha. Blockade of depletion of IkappaB-alpha by proteasome inhibitors (proteasome inhibitor I or acetyl-leucinyl-leucinyl-norleucinal) led to concomitant inhibition of NF-kappaB DNA-binding activity and expression of MIP-1alpha and MIP-1beta messenger RNA induced by beta(2) integrin ligation. These results suggest that triggering of CD11b or CD11c beta(2) integrin on primary human monocytes provides activation signals leading to nuclear translocation of NF-kappaB and subsequent secretion of MIP-1alpha and MIP-1beta that may have an important role in recruitment of other inflammatory cells during initiation of an inflammatory response.

Antibodies↗
PubMed1997

Structural interlock between ligand-binding site and stalk-like region of beta1 integrin revealed by a monoclonal antibody recognizing conformation-dependent epitope.

Integrin activation and sebsequent ligand binding to it are regulated by intracellular mechanisms called inside-out signaling, which are not fully understood and are accompanied by dynamic structural changes of the integrin molecule itself. A monoclonal antibody recognizing a conformation-dependent epitope on human beta1 integrin was produced and characterized in detail. This antibody, AG89, reacted with human integrin beta1 chain regardless of the alpha subunit. AG89 can recognize resting state beta1 integrin on the cells, but the reactivity is increased approximately 2-fold upon integrin activation by activating anti-beta1 antibodies and approximately 3-fold by Mn2+. Furthermore, occupation of the ligand-binding pocket by a soluble ligand (RGD peptide for alpha(v)beta1 and CS-1 peptide for alpha4beta1) resulted in maximum binding of AG89, indicating that the epitope for AG89 is exposed during the conformational changes of beta1 integrin upon activation/ligation. Epitope mapping by using interspecies chimeric beta1 revealed that the epitope for AG89 lies within residues 426-587, which corresponds to the cysteine-rich repeat structure located in the middle of the beta1 chain. The fact that binding of AG89 itself could activate the resting beta1 integrin indicates that exposure of the AG89 epitope in the membrane-proximal stalk-like domain and "opening" of the ligand-binding pocket at the outermost domain are physically linked. We propose that the integrin "signaling" is mediated by this direct physical transduction of conformational information along the integrin molecule.

Antibodies, Monoclonal↗
PubMed1993

Localization of beta 1-integrins in human cartilage and their role in chondrocyte adhesion to collagen and fibronectin.

In the past, proteins have been described that may be involved in chondrocyte interactions with extracellular collagen, but little is known about the role of integrins in chondrocyte-collagen interactions. Here we report on the analysis of beta 1-integrin distribution in human fetal cartilage and on the expression of integrins on fetal chondrocytes, using monoclonal and polyclonal antibodies to integrin alpha- and beta-chains. We show the presence of alpha 2-, alpha 5-, alpha 6-, alpha v-, and beta 1-chains on freshly isolated chondrocytes by surface immunofluorescence in the fluorescence-activated cell sorter and by surface iodination followed by immunoprecipitation. Affinity chromatography of bovine chondrocyte membrane proteins on a collagen-Sepharose column followed by immunoprecipitation confirmed the presence of the collagen-binding alpha 2 beta 1-integrin on chondrocytes. Chondrocyte adhesion on native collagens I and II, on fibronectin, and on laminin was completely blocked by anti-beta 1; anti-alpha 2 reduced chondrocyte binding to collagen by only 40-50%; similarly, anti-alpha 1-antibodies were also able to reduce chondrocyte binding to collagen, although alpha 1 could not be unequivocally identified on chondrocytes. Chondrocyte adhesion to fibronectin was Mg(2+)- and Ca(2+)-dependent and could be inhibited by anti-alpha 5 and by RGD peptides. Chondrocyte adhesion to native collagens is Mg(2+)-, but not Ca(2+)-dependent and RGD-independent. Interestingly, although these data point to a role of alpha 2 beta 1 in chondrocyte-collagen interactions in vitro, alpha 2 could not be visualized in sections of human fetal cartilage, in contrast to the beta 1-, alpha v-, and alpha 5-chains which were present. This suggests that alpha 2 beta 1-integrin may be involved in the assembly of a pericellular collagen matrix in vitro, but may not be required for chondrocyte-collagen interactions in intact cartilage.

Animals↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed1995

Cognate interaction between human lymphocytes and eosinophils is mediated by beta 2-integrins and very late antigen-4.

Here the cognate interactions between human eosinophils and lymphocytes are studied. These interactions were measured in a double-colored FACS analysis by applying fluorescent red eosinophils (stained with hydroethidine, 40 mumol/L) and fluorescent green lymphocytes (stained with sulfidofluorescein diacetate, 100 mumol/L) in a ratio of 1:3. When normal eosinophils were mixed with a total lymphocyte preparation in stirred suspensions (37 degrees C), no physical interaction was present between both cell types. However, the addition of phytohemagglutinin and PMA resulted in a clear aggregation response between both cell types (up to 30% of the eosinophils interacted with lymphocytes after 15 minutes). CD8(+)- and CD4(+)-positive T cells contributed equally to the heterotypic aggregation response. It is interesting that when lymphocytes were pretreated with phytohemagglutinin or eosinophils with phorbol myristate acetate and subsequently washed, the cells still interacted with unstimulated counterparts. The heterotypic interaction between lymphocytes and eosinophils is blocked by monoclonal antibodies directed against the beta-chain of the beta 2-integrins (CLB LFA1/1; CD18) and the alpha-chain of very late antigen-4 (VLA-4) (HP2/1; CD49d), indicating that both the beta 2-integrins and VLA-4 contributed to this heterotypic interaction. When eosinophils bound to PHA-treated lymphocytes, the cells exhibited an activated phenotype that was characterized by an enhanced expression of CD66b and CD11b. The cells interacted with each other provided that an intact cellular metabolism was present--that is, no interaction was seen after treatment with the glycolysis inhibitor sodium mono-iodoacetate.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
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↗
PubMedDate not supplied

Invasive behaviour of human gliomas is mediated by interindividually different integrin patterns.

BACKGROUND: Glioma invasion is still a major obstacle for successful therapy. In the past we could demonstrate that glioma invasion is mediated by different adhesion molecules of the integrin family. Here we investigated whether a common pattern of integrin profiles might be involved, potentially providing a therapeutical avenue. MATERIAL AND METHODS: Multicellular spheroids were generated out of three human cell lines (GaMG, U373, U251) and from tumor biopsies of 9 human glioblastomas. After confrontation with rat brain aggregates, functional blocking antibodies against different integrin subunits (alpha 2, alpha 3, alpha v, alpha 1, alpha v beta 3, alpha v beta 5) or four different disintegrines (kistrin, echistatin, eristostatin, flavoridin) were added. Integrin patterns of the human cell lines/specimens were determined by FACScan or immunohistochemistry. RESULTS: In cell lines, antibodies against alpha 2, alpha 3, alpha v and alpha v beta 5 effectively reduced invasion into rat brain aggregates. Little effect could be observed with the anti-beta 1- or with anti-alpha v beta 3- antibodies. In primary tumor specimens, however, a different invasion pattern in regard to its integrin dependency emerged with antibodies against the alpha 3-chain or the alpha v beta 3 integrin being the most effective. Invasion of primary tumor tissue into the brain aggregates was by far more aggressive compared to that of the cell lines. Accordingly, it was less influenced by integrin antibodies. The disintegrines affected migration of glioma cells on purified ECM substrates in a heterogeneous matter, but had no impact on tumor invasion into brain aggregates. CONCLUSION: Although invasion of human gliomas is mediated by integrins, due to the heterogeneity of its dependency on different integrins this approach seems not to be appropriate to sufficiently alter glioma invasion in a therapeutical neuro-oncological setting.

Aged↗