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PubMed1990

Expression of receptors for extracellular matrix proteins in human endothelial cells.

The interaction with matrix components of the basal membrane is an important factor in the control of vascular endothelial cell function in both normal and pathological conditions. In the present work we define integrin receptors in vascular endothelial cells and analyze whether their expression is affected by endothelial cell activators. Using in vitro adhesion tests we show that human endothelial cells (HEC) can attach and spread on substrates coated with several matrix components including fibronectin, laminin, collagen type IV, fibrinogen and vitronectin. Using specific antibodies we detect integrin receptor complexes of the beta 1 and beta 3 families that can support adhesion of HEC to the above matrix proteins. These are the alpha 2/beta 1 collagen receptor, the alpha 3/beta 1 receptor for fibronectin, collagens and laminin, the alpha 5/beta 1 fibronectin receptor, the alpha 6/beta 1 laminin receptor and the alpha V/beta 3 receptor for vitronectin and fibrinogen. When HEC are exposed to a combination of tumor necrosis factor alpha (TNF alpha) and immune interferon (IFN-gamma) the amount of the alpha V/beta 3 vitronectin receptor at the cell surface was decreased by a factor of 50-70%, while the beta 1 integrin complexes were not affected. HEC cells thus express receptors for several matrix components and inflammatory mediators such as TNF alpha and IFN-gamma can selectively alter the expression of some of them.

Cell Adhesion↗
PubMed1993

Integrins as differential cell lineage markers of primary liver tumors.

This study analyzed new cell lineage markers for the differential diagnosis between hepatocellular carcinoma (HCC) and cholangiocarcinoma (ChC), as well as the potential pathways of cell-cell and cell-extracellular matrix interactions of neoplastic liver cells during tumor spread and invasion, by comparing the expression of (VLA) integrins, vitronectin receptor, and neural cell adhesion molecule in normal, inflamed, and neoplastic human liver biopsies. All cases of liver cell adenoma and well-differentiated HCC expressed the same set of integrins as observed in normal liver tissue, i.e., VLA-alpha 1 and VLA-beta 1. Poorly differentiated HCC also expressed VLA-alpha 1 and VLA-beta 1, but in addition de-novo expressed VLA-alpha 2, VLA-alpha 3, VLA-alpha 6 and vitronectin receptor. All cases of well-differentiated ChC expressed an identical integrin immunoprofile as observed in normal bile duct epithelium, i.e., VLA-alpha 2, VLA-alpha 3, VLA-alpha 6, VLA-beta 4 and vitronectin receptor, whereas poorly differentiated ChC showed a markedly decreased expression of these integrin subunits. VLA-alpha 1 was constantly absent from all cases of ChC, whereas VLA-beta 4 was never expressed by HCC. Neural cell adhesion molecule, exclusively expressed by proliferating reactive bile ductules in cholestatic and regenerating liver, was constantly absent from both malignant neoplasms. In conclusion, the integrin make up of various liver tumors closely follows that of their normal counterparts. Differences in integrin receptor expression vary according to the cellular origin of the tumors and are associated with a poor differentiation. Our findings suggest that immunohistochemical staining for VLA-alpha 1 and VLA-beta 4 integrin subunits, which highlight the cellular phenotype of the two neoplasms, might be a helpful tool in the differential diagnosis between HCC and ChC.

Adenoma↗
PubMed1993

Regulation of complement membrane attack complex formation in myocardial infarction.

Recent studies have suggested that the complement (C) system is involved in the development of tissue injury of myocardial infarction. As it is not known why the strictly controlled C system starts to react against autologous heart tissue, we have analyzed the expression of various membrane regulators of C (CR1, DAF, MCP, CD59, C8 binding protein) and the pattern of deposition of C components and plasma C regulators (C4b binding protein and vitronectin) in normal (n = 7) and infarcted (n = 13) human myocardium. In the infarcted myocardium deposits of the C membrane attack complex (MAC) were observed by immunofluorescence microscopy, and lesions resembling the transmembrane channels of MAC were detected by transmission electron microscopy. CD59 and C8 binding protein were strongly expressed by muscle cells of normal myocardial tissue. Little or no CR1, MCP, and DAF was observed on these cells. The assembly of MAC was accompanied by the deposition of vitronectin (S-protein) and C4b binding protein in the infarcted areas of myocardium. In accordance with our earlier results the expression of CD59 but not of C8 binding protein was clearly diminished in the lesions. The results show that C8 binding protein, vitronectin, and C4b binding protein do not prevent complement attack against the infarcted myocardium but rather become codeposited with the MAC. Ischemia-induced transformation of nonviable cells into complement activators, acquired loss of resistance to the MAC by shedding of CD59, and recruitment of multifunctional serum proteins by MAC could thus constitute a general process aimed at the clearance of injured tissue.

Aged↗
PubMed1996

Matrix proteins with high affinity for calcium ions are associated with mineralization within the elastic fibers of pseudoxanthoma elasticum dermis.

Ultrathin sections from the dermis of five normal subjects and from 10 patients suffering from pseudoxanthoma elasticum (PXE) were analyzed by immunoelectron microscopy with the aim of identifying and localizing proteins associated with the mineral precipitates within the altered elastic fibers. Serial sections were processed by indirect immunogold cytochemistry using primary antibodies against human fibronectin, vitronectin, bone sialoprotein, alkaline phosphatase, osteonectin, and osteopontin. In the latter two cases, antibodies against synthetic peptides were also used. The results indicate that normal elastic fibers contained osteopontin, and that this protein was associated with the apparently normal elastin as well as with the needle-shaped mineral precipitates in the elastic fibers of patients. On the contrary, significant amounts of vitronectin, alkaline phosphatase and, less, of bone sialoprotein were associated with the polymorphous mineral precipitates inside the elastic fibers. Large amounts of osteonectin and fibronectin, together with vitronectin, were localized on the microfilament aggregates, which were often associated with altered elastic fibers in PXE dermis and were never visualized in the dermis of control subjects. The results seem to indicate once more that PXE is a complex disorder of the fibroblast synthetic control. Elastic fiber mineralization might be considered a secondary event, which could depend on the abnormal synthesis and accumulation within the elastic fibers of proteins that are normally involved in mineralization processes.

Adolescent↗
PubMed1996

Re-epithelialization of normal human excisional wounds is associated with a switch from alpha v beta 5 to alpha v beta 6 integrins.

During cutaneous wound repair, keratinocytes move laterally across the wound surface. For this lateral movement epidermal cells must disassemble their tenacious connections to the basement membrane and their neighbouring cells, and express surface receptors that permit translocation over the wound surface extracellular matrix. If the basement membrane is disrupted, the epidermis migrates over a provisional matrix that contains fibrinogen, fibronectin, vitronectin and tenascin. Although alpha 5 beta 1 integrin, a fibronectin receptor, is expressed by human epidermis during re-epithelialization of excisional and incisional wounds, the spatial and temporal patterns of vitronectin, tenascin, and other fibronectin receptors are less clear. Other potential receptors include alpha v beta 5 for vitronectin and alpha v beta 6 for fibronectin and tenascin. To study provisional matrix integrin expression during human wound healing, full-thickness 4-mm punch biopsies were performed on the inner surface of the upper arm in adult volunteers. At 3, 7 and 14 days after injury wound sites were excised, bisected, quick frozen in liquid nitrogen, and examined for the expression of alpha 5, beta 1, alpha v, beta 5 and beta 6. At 3 days, alpha 5 beta 1 and alpha v beta 5, but not alpha v beta 6, appeared around the basal and suprabasalar cells of the migrating epidermis. At 7 days, alpha 5 beta 1, alpha v beta 5, and alpha v beta 6 appeared around the perimeter of the basal cells of the migrating epidermis. By 14 days, when re-epithelialization was complete, all basal and suprabasalar cells overlying the wound expressed alpha 5 beta 1 and alpha v beta 6, but not alpha v beta 5. Thus, alpha v appeared to switch its heterodimeric association from beta 5 to beta 6 subunit during re-epithelialization.

Adult↗
PubMed1997

[Age-dependent distribution of collagen and glycoproteins in the blood vessels of the human uterine tube].

Localization and distribution of both collagen (types I, III, IV, V, VI) and glycoproteins (undulin, fibronectin, laminin, tenascin, vitronectin) in the blood vessels of the human uterine tube were investigated immunohistochemically. In the tubal arteries of premenopausal and postmenopausal women, type I, III, V and VI collagen and undulin have very characteristic distribution patterns. The proteins could be observed predominantly in both the intima and a zone between media and adventitia. This zone was condensed in arteries after the menopause. With increasing age, the reactivity of type I, III, V and VI collagen and undulin increased even more. Furthermore, the glycoproteins fibronectin, laminin, tenascin and vitronectin were also detected. Relating to immunohistochemical reactivity of these glycoproteins no age-dependent differences in the tubal arteries existed. The staining intensity of fibronectin was always weaker compared to that of undulin. Similarly to laminin and type IV collagen fibronectin was detected in intima and media. Tenascin was also found in blood vessels and prominently in the media and intima. Vitronectin was associated with fine granular and fibrous structures in the intima and the media of all arterial and venous vessels. The enhanced perimenopausal production of both collagen and undulin in the arterial wall should lead to changes of the elastic properties of the tubal arteries.

Adult↗
PubMed1997

Integrin function in osteoclasts.

Integrins are a large family of heteromeric cell surface receptors composed of non-covalently bound alpha and beta subunits which interact with extracellular matrix molecules, serum constituents and the adhesion molecules of the immunoglobulin family. The extracellular domains of many integrins recognize the RGD (Arg-Gly-Asp) tripeptide found in several extracellular macromolecules such as fibronectin, vitronectin, fibrinogen and osteopontin. The vitronectin receptor, alpha v beta 3 integrin, is highly expressed in osteoclasts, the bone resorbing cells, and binds many of these RGD containing proteins including osteopontin, which is abundant in bone. Antibodies to alpha v beta 3, RGD peptides and RGD containing proteins such as echistatin, and kistrin were shown to inhibit bone resorption in vitro and in vivo. The identity of the alpha v beta 3 natural ligand and its mode of action in bone are so far not known. In addition to the very high levels of alpha v beta 3, mammalian osteoclasts also express alpha 2 beta 1, a collagen/laminin receptor and alpha v beta 1, another vitronectin receptor. Signaling events that follow substrate recognition by osteoclasts are not well understood. RGD containing peptides and proteins modulate [Ca2+] transients in osteoclasts and phosphatidylinositol 3-kinase and pp60c-src are associated with alpha v beta 3 in these cells. alpha v and beta 3 genes were shown to be regulated by the calciotropic hormone 1,25(OH)2D3 and by a number of cytokines known to be modulators of bone metabolism. In summary, elucidation of the interactions of osteoclast integrins with components of bone matrix, may lead to further understanding of the mechanism of bone resorption.

Animals↗
PubMed1998

A peptidomimetic antagonist of the integrin alpha(v)beta3 inhibits Leydig cell tumor growth and the development of hypercalcemia of malignancy.

The integrin alpha(v)beta3 interacts with the arginine-glycine-aspartic acid (RGD) tripeptide recognition sequence of a variety of extracellular matrix proteins. Recent studies show that alpha(v)beta3 plays an important role in tumor-induced angiogenesis and tumor growth and that antagonists of alpha(v)beta3 inhibit angiogenic processes that include endothelial cell adhesion and migration. Consequently, we reasoned that an RGD-based peptidomimetic antagonist of alpha(v)beta3 might inhibit tumor angiogenesis and tumor growth in vivo. An RGD-peptidomimetic library was screened to identify antagonists of vitronectin binding to alpha(v)beta3, and the compounds chosen were modified to produce selective and potent inhibitors of alpha(v)beta3. One of these compounds, beta-[[2-2-[[[3-[(aminoiminomethyl)amino]-phenyl]carbonyl]amino]ac etyl]amino]-3,5-dichlorobenzenepropanoic acid (SC-68448), inhibited vitronectin binding to both alpha(v)beta3 and the closely related platelet receptor, alpha(IIb)beta3, in a dose-responsive manner. SC-68448 inhibited vitronectin binding to alpha(v)beta3 (IC50, 1 nM) and fibrinogen binding to the platelet receptor alpha(IIb)beta3 (IC50, >100 nM), demonstrating that SC-68448 was 100-fold more potent as an inhibitor of alpha(v)beta3 versus alpha(IIb)beta3. In cell-based studies, SC-68448 inhibited alpha(v)beta3-mediated endothelial cell proliferation in a dose-dependent manner but did not inhibit tumor cell proliferation, suggesting that effects on endothelial cell proliferation were not due to SC-68448-induced cytotoxicity. In accord with these results, SC-68448 inhibited angiogenesis in vivo in a basic fibroblast growth factor-induced rat corneal neovascularization model. A xenogeneic severe combined immune deficiency mouse/rat Leydig cell tumor model was developed for testing SC-68448 as an inhibitor of tumor growth in vivo. Rat Leydig cell tumors grew rapidly in severe combined immune deficiency mice and produced humoral hypercalcemia of malignancy. SC-68448 inhibited the growth of the tumors in mice by up to 80% and completely blocked the development of hypercalcemia. Together, these results demonstrate the feasibility of antitumor therapies based upon the development of nontoxic small molecule pharmacological antagonists of integrin alpha(v)beta3.

Animals↗
PubMed1998

Integrin alphavbeta5 participates in the binding of photoreceptor rod outer segments during phagocytosis by cultured human retinal pigment epithelium.

PURPOSE: To examine the expression of integrin vitronectin receptors (integrins alphavbeta3 and alphavbeta5) in native human fetal retinal pigment epithelium (RPE) and cultured hunman fetal RPE and to examine the role of RPE VnRs in the phagocytosis of photoreceptor rod outer segments (ROS). METHODS: Monoclonal antibodies against human integrin subunit alphav and heterodimers alphavbeta3 (LM609) and alphavbeta5 (P1F6) were used to label freshly isolated human fetal RPE explant and cultured human fetal RPE and to immunoprecipitate membrane proteins from cultured human RPE. Effects of antibodies and peptides that inhibit integrin vitronectin receptors on phagocytosis of ROS by RPE were determined using cultured human fetal RPE and fluorescein-labeled bovine outer segments. RESULTS: Antibodies against integrin subunit alphav and against alphavbeta5 (P1F6) labeled the RPE apical membrane in both native tissue and cultured RPE, while anti-alphavbeta3 antibody (LM609) labeled less than 1% of cultured RPE and did not label native RPE. Antibodies against alphav and alphavbeta5 P1F6 also immunoprecipitated 2 protein bands corresponding to integrin subunits alphav and beta5 from a membrane extract of cultured human RPE. The peptide Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP, 1 mM) inhibited the total ROS uptake (externally bound and ingested) by 48% (P < 0.001) and ingestion of ROS by 37% (P < 0.001). Antibody PIF6 (50 microg/ml) inhibited the total ROS uptake and the ingestion of ROS by 63% (P < 0.001) and 43% (P < 0.01), respectively. CONCLUSIONS: The integrin alphavbeta5 vitronectin receptor is expressed on the apical membrane of human RPE and participates in the binding of photoreceptor ROS during phagocytosis by cultured human RPE.

Animals↗
PubMedDate not supplied

Effects of extracellular matrix constituents on the attachment of human oral epithelial cells at the titanium surface.

This in vitro study attempts to delineate the role of extracellular matrix (ECM) constituents at the epithelial tissue-implant interface. To know which ECM constituents have a beneficial influence on the behavior of epithelial cells, the attachment, proliferation, morphologic pattern, and differentiation or cytoskeletal organization of human oral epithelial cells on ECM-coated (type IV collagen, fibronectin, type I collagen, laminin, and vitronectin) and noncoated titanium surface have been evaluated and compared. In each experiment comparing commercially pure titanium and oxygen plasma-cleaned titanium, the same ECM constituents were used. In this study, type IV collagen could provide an excellent substratum for epithelial cell attachment on titanium surface, but vitronectin-coated titanium revealed lower effectiveness for attachment of epithelial cells than noncoated titanium. These results suggested that type IV collagen could be used as a means for obtaining good epithelial seal, whereas vitronectin could be used to restrain the attachment of epithelium to dental implants.

Adult↗
PubMed1993

Microglia in degenerative neurological disease.

Microglia express many leukocyte surface antigens which are upregulated in such chronic degenerative neurological diseases as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). These surface antigens include leukocyte common antigen, immunoglobulin Fc receptors, MHC class I and class II glycoproteins, beta 2-integrins, and the vitronectin receptor. Ligands for these receptors are also found. They include immunoglobulins, complement proteins of the classical pathway, T lymphocytes of the cytotoxic/suppressor and helper/inducer classes, and vitronectin. T lymphocytes marginate along capillary venules, with some penetrating into the tissue matrix. Immunoglobulins and complement proteins are synthesized locally in brain, although they may also come from the bloodstream if the blood-brain barrier is compromised. The membrane attack complex, which is formed from C5b-9, the terminal components of complement, has been identified in AD and multiple sclerosis brain tissue. In addition, proteins designed to defend against bystander lysis caused by the membrane attack complex, including protectin, C8 binding protein, clusterin, and vitronectin, are associated with damaged neuronal processes in AD. Autodestruction may play a prominent part in these 2 diseases.

Antigens, Surface↗
PubMed2006

Adhesion of mesenchymal stem cells to polymer scaffolds occurs via distinct ECM ligands and controls their osteogenic differentiation.

The osteogenic potential of mesenchymal stem cells (MSCs) cultured on poly(lactide-co-glycolide) (PLGA) or poly(caprolactone) (PCL), two widely used polymeric biomaterials that have been reported to differentially support osteogenic differentiation, was compared in these studies. Here we report that MSCs cultured in 3-D PLGA scaffolds for up to 5 weeks significantly upregulate osteocalcin gene expression levels. By contrast, osteocalcin expression was markedly downregulated in 3-D PCL-based constructs over the same time course. We hypothesized that differential adsorption of extracellular matrix (ECM) proteins present in serum-containing culture medium and subsequent differences in integrin-mediated adhesion are responsible for these differences, and tested this hypothesis using thin (2-D) polymeric films. Supporting this hypothesis, significant amounts of fibronectin and vitronectin deposited onto both materials in serum-containing osteogenic media, with type-I collagen present in lower amounts. Adhesion-blocking studies revealed that MSCs adhere to PCL primarily via vitronectin, while type-I collagen mediates their attachment to PLGA. These adhesive mechanisms correlated with higher levels of alkaline phosphatase (ALP) activity after 2 weeks of monolayer culture on PLGA versus PCL. These data suggest that the initial adhesion of MSCs to PLGA via type-I collagen fosters osteogenesis while adhesion to PCL via vitronectin does not, and stress the need for an improved molecular understanding of cell-ECM interactions in stem cell-based therapies.

Cell Adhesion↗
PubMed1993

Expression of alpha v and beta 3 integrin subunits in rat osteoclasts in situ.

Recent findings suggest that the vitronectin receptor, a member of the integrin family, plays an important role in the attachment of osteoclasts to bone matrix. We report here the localization by in situ hybridization of the mRNA for the alpha and beta subunits of the vitronectin receptor in rat bone sections. To generate the rat-specific RNA probes used in this study, we cloned cDNA fragments of integrin chains alpha v, beta 3, and beta 5 by the polymerase chain reaction from rat cDNA. These fragments share 86-91% homology with the respective human sequences. In situ hybridization localized the alpha v and beta 3 mRNAs to regions undergoing extensive bone resorption. The histologic appearance and prestaining of bone sections for tartrate-resistant acid phosphatase (TRAP) indicated the presence of these mRNAs in osteoclasts. These observations support immunohistochemical findings that osteoclasts express high levels of the vitronectin receptor, confirm the identity of this receptor as integrin alpha v/beta 3, and suggest that osteoclasts may actively synthesize these molecules.

Amino Acid Sequence↗
PubMed2004

Carbohydrates and glycoproteins involved in bovine fertilization in vitro.

In the present study, efforts were made towards identifying carbohydrates and glycoproteins involved in bovine in vitro fertilization (IVF). In vitro matured cumulus-oocyte complexes (COCs) were inseminated in the presence of a variety of carbohydrates and glycoproteins to determine which glycoconjugates act as competitive inhibitors of oocyte penetration. Among the carbohydrates and glycoproteins tested, D-mannose, fucoidan, dextran sulfate, and fibronectin were the most potent inhibitors of oocyte penetration (90% or more inhibition), while L-fucose and vitronectin inhibited the penetration rate to a lesser extent (around 50% inhibition). Other carbohydrates caused less than 40% inhibition (i.e., D-galactose, N-acetyl-D-galactosamine, D-fucose, and sialic acid) or were not effective as inhibitors of oocyte penetration (i.e., mannan, N-acetyl-D-glucosamine, dextran, and heparan sulfate). Heparin was the only carbohydrate that significantly increased the penetration rate. To exclude a possible toxic effect on spermatozoa, sperm motility was evaluated over time by means of computer-assisted sperm analysis in the presence of carbohydrates and/or glycoproteins that inhibited the penetration rate with 40% or more. L-fucose, dextran sulfate, and vitronectin did not significantly influence total and progressive sperm motility, whereas D-mannose, fucoidan, and fibronectin caused a significant, but slight reduction in both motility parameters. These results are indicative for the involvement of D-mannose, L-fucose, fucoidan, dextran sulfate, fibronectin, and vitronectin in bovine IVF.

Animals↗
PubMed2002

Cell adhesion regulates the plasminogen activator inhibitor-1 gene expression in anchorage-dependent cells.

Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of both tissue- and urokinase-type plasminogen activators (t-PA, u-PA). PAI-1 also regulates the attachment of cells to the adhesive glycoprotein vitronectin (VN). PAI-1 gene expression has been observed in various cell types, and many regulatory factors have been identified to play a role in PAI-1 gene transcription. The complete picture of how the PAI-1 gene is expressed when cells adhere to a culture plate has not been fully elucidated. We found that in anchorage-dependent cells, PAI-1 gene was up-regulated when cells were beginning to attach to a culture dish and was down-regulated when cells had attached completely. The PAI-1 gene expression was induced only in adhered cells but not in non-adhered cells. The regulation of PAI-1 protein was also found in both culture medium and cell lysate when cells were attached to a culture dish. Our experiment indicates that vitronectin and fibronectin, as components of ECM, may be the factors involved in the regulation of PAI-1 gene expression. PAI-1, as an inhibitor of the interaction between vitronectin and integrin alphavbeta3, may also be a regulator of its own expression.

Blotting, Northern↗
PubMed2001

A novel human gene (SARM) at chromosome 17q11 encodes a protein with a SAM motif and structural similarity to Armadillo/beta-catenin that is conserved in mouse, Drosophila, and Caenorhabditis elegans.

A novel human gene, SARM, encodes the orthologue of a Drosophila protein (CG7915) and contains a unique combination of the sterile alpha (SAM) and the HEAT/Armadillo motifs. The SARM gene was identified on chromosome 17q11, between markers D17S783 and D17S841 on BAC clone AC002094, which also included a HERV repeat and keratin-18-like, MAC30, TNFAIP1, HSPC017, and vitronectin genes in addition to three unknown genes. The mouse SARM gene was located on a mouse chromosome 11 BAC clone (AC002324). The SARM gene is 1.8 kb centromeric to the vitronectin gene, and the two genes share a promoter region that directs a high level of liver-specific expression of both the SARM and the vitronectin genes. In addition to the liver, the SARM gene was highly expressed in the kidney. A 0.4-kb antisense transcript was coordinately expressed with the SARM gene in the kidney and liver, while in the brain and malignant cell lines, it appeared independent of SARM gene transcription. The SARM gene encodes a protein of 690 amino acids. Based on amino acid sequence homology, we have identified a SAM motif within this derived protein. Structure modeling and protein folding recognition studies confirmed the presence of alpha-alpha right-handed superhelix-like folds consistent with the structure of the Armadillo and HEAT repeats of the beta-catenin and importin protein families. Both motifs are known to be involved in protein-protein interactions promoting the formation of diverse protein complexes. We have identified the same conserved SAM/Armadillo motif combination in the mouse, Drosophila, and Caenorhabditis elegans SARM proteins.

Amino Acid Motifs↗
PubMed2002

Peripheral nerve extracellular matrix remodeling in Charcot-Marie-Tooth type I disease.

Charcot-Marie-Tooth type 1 disease (CMT1) is a group of inherited demyelinating neuropathies caused by mutations in genes expressed by myelinating Schwann cells. Rather than demyelination per se, alterations of Schwann cell-axon interactions have been suggested as the main cause of motor-sensory impairment in CMT1 patients. In an attempt to identify molecules that may be involved in such altered interactions, the extracellular matrix (ECM) remodeling occurring in CMT1 sural nerves was studied. For comparison, both normal sural nerves and sural nerves affected by neuropathies of different origin were used. The study was performed by immunohistochemical analysis using antibodies against collagen types I, III, IV, V, and VI and the glycoproteins fibronectin, laminin, vitronectin and tenascin. Up-regulation of collagens, fibronectin and laminin was commonly found in nerve biopsy specimens from patients affected by CMT1 and control diseases, but higher levels of overexpression were usually observed in CMT1 cases. On the other hand, vitronectin and tenascin appeared preferentially induced in CMT1 compared to other pathologies investigated here. Vitronectin, whose expression in normal nerves was limited to perineurial layers and to the walls of epineurial and endoneurial vessels, became strongly and diffusely expressed in the endoneurium in most CMT1 biopsy specimens. The expression of tenascin, confined to the perineurium, to vessel walls and to the nodes of Ranvier in normal nerves, was displaced and extended along the internodes of several nerve fibers in the majority of CMT1 nerves. Thus, compared with our pathological controls CMT1 seemed to determine the most extensive remodeling of peripheral nerve ECM.

Adolescent↗
PubMed1990

Alteration of cellular adhesion by heat shock.

Chinese hamster ovary (CHO) cells were analyzed for their ability to reassemble microfilament bundles, to remain attached to a tissue culture surface, or to initiate and complete attachment onto a substrate after heat shock (45 degrees C/10 min). The cells remained attached to the tissue culture surface during and after the heat shock while the actin microfilament bundles were reversibly disrupted. Heat shock inhibited the ability of the cells to initiate and complete attachment onto a new tissue culture surface or onto a plastic surface coated with vitronectin. An inspection of the proteins present in substrate-attached material (SAM) revealed 11 major proteins containing glucosamine whose apparent Mr values were 250,000, 200,000, 150,000, 140,000, 90,000, 86,000, 82,000, 68,000, 54,000, 47,000, and 46,000. Three of the proteins (p200, p150, and p46) bound to wheat germ agglutinin while p150 and p140 bound to concanavalin A. The composition of the 11 proteins of the SAM fraction synthesized previous to the heat shock was not altered during heat shock. However, the appearance of the newly synthesized proteins in the SAM fraction was delayed by heat shock (0.5 h for p150 and 6 h for p82). The ability of heat-shocked cells to reattach onto a vitronectin-coated surface correlated with the appearance of newly synthesized p150 and p82 in the SAM fraction. Our results suggest that in addition to the microfilament bundles, heat shock may reversibly disrupt the cellular adhesion site. Further, p150 and p82, proteins whose appearance in the SAM fraction is delayed by heat shock, may be involved in the cellular attachment onto substrates, including vitronectin.

Actin Cytoskeleton↗