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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Basement membrane (BM) is a highly specialized extracellular matrix (ECM), which is associated with epithelia and endothelia. BM provide epithelia with structural support and also regulate cell behavior. The liver contains a unique ECM within the space of Disse, which consists of basement membrane constituents as well as fibrillar ECM molecules. Changes in composition of this ECM are considered detrimental for viability of hepatocytes during progression of liver disease. Mouse tumor-derived BM preparations, such as Matrigel, which are commonly used as a model for BM in vitro, differ significantly in their composition from liver BM present in vivo. In order to gain further insights into the role of BM in the regulation of hepatocyte behavior in health and disease, we generated a liver-derived basement membrane matrix (LBLM). LBLM allowed investigation of BM-hepatocyte interactions in vitro. Here we report a novel approach of generating a liver-derived basement membrane matrix by separate isolation of type IV collagen, laminin, nidogen, and heparan sulfate proteoglycans, and subsequent reconstitution into a matrix-like gel. Adhesion of primary human hepatocytes to LBLM was increased and the rate of de-differentiation was decreased compared to hepatocyte cultivation on Matrigel or type I collagen matrix. Primary human hepatocytes maintained their differentiated epithelial phenotype on LBLM isolated from normal human livers for more than 21 days, whereas they de-differentiated rapidly on LBLM isolated from cirrhotic human livers. Normal human LBLM contains a unique isoform composition of type IV collagen, namely alpha1 (IV), alpha2(IV), alpha4(IV), and alpha6(IV) chains, whereas cirrhotic LBLM contains only alpha1(IV) and alpha2(IV) isoforms, albeit present in increased amounts. These findings suggest that the composition of liver basement membrane is important for the maintenance of hepatocyte viability and provide anti-de-differentiation clues.
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PMID:De-differentiation of primary human hepatocytes depends on the composition of specialized liver basement membrane. 1644 1

Adhesion of mononuclear cells to the vascular endothelium and their subsequent transmigration into the arterial wall represent key events in the pathogenesis of arteriosclerosis. In previous studies we have shown that high density lipoproteins (HDL) and the HDL-associated sphingosylphosphorylcholine (SPC) have the ability to suppress the TNF-alpha-induced expression of endothelial cell E-selectin. However, the current understanding of the mechanism by which HDL reduces the expression of E-selectin is still incomplete. In the present study we show that interaction of the HDL-associated sphingosylphosphorylcholine and sphingosylgalactosyl-3-sulfate (lysosulfatide, LSF) with the G-protein-coupled EDG receptor initiates a signalling cascade that activates the protein kinase Akt and reduces the E-selectin, ICAM-1 and VCAM-1 expression on protein and mRNA level. This signalling cascade is consistently associated with a reduced translocation of TNF-alpha-activated NF-kappaB into the cell nucleus. The suppressor effect of SPC and LSF is completely reverted by inhibition of the phosphatidylinositol- 3-kinase/Akt pathway. We conclude that the antiatherogenic/antiinflammatory effect of lysosphingolipids depends on a competitive interaction of EDG receptor-induced inhibition and TNF-alpha-initiated stimulation of NF-kappaB translocation into the cell nucleus thereby preventing or stimulating inflammatory events in atherogenesis.
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PMID:The antiatherogenic and antiinflammatory effect of HDL-associated lysosphingolipids operates via Akt -->NF-kappaB signalling pathways in human vascular endothelial cells. 1645 77

A biopsy procedure was developed to provide serial kidney samples from standing steers. Ten clinically normal steers were given intramuscular injections of gentamicin sulfate, 4 mg/kg body weight. Renal biopsy was performed at 5 separate times. After feed was withheld for 24 h, laparoscopic surgery was performed in standing stocks. Acepromazine, xylazine, and butorphanol were used for sedation and analgesia, and 2% lidocaine was used for local anesthesia. Two incisions approximately 2 cm long were made in the paralumbar fossa to allow for trocar introduction. The abdomen was insufflated with CO2 and, with endoscopic guidance, a biopsy forceps used to remove a kidney sample 2 to 3 mm in diameter, by either a left or a right abdominal approach. Each operation was recorded on videotape, and images were also captured with a digital medical device system. Respiration, heart rate, temperature, appetite, attitude, and postural positions were evaluated at 12, 24, 48, and 72 h after surgery. The 51 laparoscopic procedures provided 48 renal samples (approximately 100 mg each). The 1st and 2nd samples were from the right kidney, and the 3rd sample was from either the left or the right kidney; the 4th and 5th samples were from the left kidney. Adhesions made an approach from the right side difficult for the 3rd sample. No clinical changes were observed in 9 steers after the procedure. One steer died after the 3rd procedure owing to hemorrhage.
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PMID:Development of a technique for serial bilateral renal biopsy in steers. 1663 40

Adhesion of Plasmodium falciparum infected erythrocytes (IE) to placental chondroitin-4-sulfate (CSA) has been linked to the severe disease outcome of pregnancy-associated malaria. Consequently, sulfated polysaccharides with inhibitory capacity may be considered for therapeutic strategies as anti-adhesive drugs. During in vitro screening a regioselectively modified cellulose sulfate (CS10) was selected as prime candidate for further investigations because it was able to inhibit adhesion to CSA expressed on CHO cells and placental tissue, to de-adhere already bound infected erythrocytes, and to bind to infected erythrocytes. Similar to the undersulfated placental CSA preferred by placental-binding infected erythrocytes, CS10 is characterized by a clustered sulfate pattern along the polymer chain. In further evaluation of its effects on P. falciparum interactions with host erythrocytes, we now show that CS10 inhibits the in vitro asexual growth of parasites in erythrocytes. Furthermore, we show that CS10 interferes with C1 of the classical complement pathway but not with MBL of the lectin pathway. In order to gain insights into the possible interactions of CS10 with known parasite receptors at the molecular level, we designed 3D-structures of characteristic stretches of CS10. CS10 fragments with clustered sulfate groups showed complex patterns of hydrophobic and hydrophilic patches most likely suitable for interactions with protein binding partners. The significance of CS10 interactions with the complement system as well as its anti-malarial effect for prospective drug application are discussed.
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PMID:Regioselectively modified sulfated cellulose as prospective drug for treatment of malaria tropica. 1711 75

Adhesion is a crucial and prerequisite step for Lactobacillus colonization in the digestive tract which subsequently confers its probiotic effects on the host. The aim of this report was to identify and purify a novel adhesion-associated protein which mediates the adherence of a new strain of Lactobacillus, L15, to intestinal mucus from flounder. It was shown that surface proteins were involved in the adhesion of L15 to flounder mucus. The adhesion efficiencies of this strain were significantly decreased from 16.0% to 5.8% after extraction of L15 with 5 M LiCl and were further inhibited to 3.6% by blocking with an L15 cell extract containing surface proteins. The adhesion-associated protein in the cell extract was visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and was identified by Western blotting with sulfo-N-hydroxysuccinimide-biotin (B-NHS)-labeled crude mucus as a 61.8 kDa protein. The identical protein could be purified from L15 whole cell proteins by affinity chromatography using Sepharose, covalently coupled with crude mucus. It was demonstrated that the adhesion-associated protein was a new adhesive protein. Its characteristics and similarities with other known adhesive proteins need further investigation.
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PMID:Identification and purification of a novel adhesion-associated protein in a new strain of Lactobacillus, L15, from flounder (Paralichthys olivaceus). 1735 Jan 86

Adhesion of circulating monocytes to vascular endothelial cells, a critical step in both inflammation and atherosclerosis, is mediated by cross-linkage of adhesion molecules expressed on the surface of both cell types. Dietary flavonoids have been shown to have anti-inflammatory properties, decreasing the expression of cell adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) on endothelial cells. However, flavonoids are efficiently metabolised during absorption and the forms reaching the systemic circulation are glucuronidated, sulphated and methylated. Most previous in vitro studies of the effects of flavonoids have used the parent compounds at concentrations far higher than those physiologically achievable. We investigated the ability of quercetin and its human metabolites, at physiological concentrations (2 micromol/L and 10 micromol/L), to attenuate the inflammation-induced upregulated expression of VCAM-1, ICAM-1 and of the chemokine, monocyte chemoattractant protein-1 (MCP-1), in human umbilical vein endothelial cells (HUVECs), at the protein and transcript levels. Quercetin treatment reduced the inflammation-induced over-expression of VCAM-1 and ICAM-1 (protein and transcript) in HUVECs. Quercetin also inhibited MCP-1 gene expression. However, quercetin 3'-sulfate, quercetin 3-glucuronide and 3'-methylquercetin 3-glucuronide (isorhamnetin 3-glucuronide) generally exhibited either a reduced ability to inhibit the expression of these molecules compared with the parent aglycone or had no effect. However, all three metabolites inhibited VCAM-1 cell surface expression at 2 micromol/L. These results indicate that both quercetin and its metabolites, at physiological concentrations, can inhibit the expression of key molecules involved in monocyte recruitment during the early stages of atherosclerosis.
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PMID:Comparative effects of quercetin and its predominant human metabolites on adhesion molecule expression in activated human vascular endothelial cells. 1788 Sep 82

New evidence about diabetic microangiopathy has enabled us to identify an integrated pathogenesis of diabetic complications, including classic metabolic pathways induced by hyperglycaemia, insulin-resistance, hyperinsulinaemia, hormonal alterations and growth factors. Oxidative stress is the most important cause of endothelial damage inducing leukocyte adhesion, altered coagulation and inflammation. Adhesion molecules are a marker of endothelial damage and a potential therapeutic target. Changes in the extracellular matrix induced by TGFbeta1 and lower levels of eparan-sulfate, increased thickness of basement membranes and loss of pericytes are early events of diabetic retinopathy and diabetic nephropathy. Capillary rarefaction produced by genetic factors or by fetal undernourishment contributes to the beginning of insulin-resistance and hypertension. Psychophysical tests, electroretinogram and evoked potentials show retinal functional alterations; fundoscopy and retinal fluorescein angiography show retinal anatomic alterations. The diagnosis of diabetic neuropathy is based not only on traditional neurological examination and electroneurograms, but also on neurothesiometry for sensory testing. Medical treatment of diabetic microangiopathy is based on control of glycaemia, lipemia and blood pressure using glytazones, ACE-inhibitors, angiotensin II receptor antagonists and statins. New knowledgeabout microangiopathy pathogenesis suggests potential drugs for its therapy (ruboxistaurin, AGE-inhibitors, angiopoietin-1 and anti-VEGF, etc.), not yet on sale.
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PMID:Diabetic microangiopathy: physiopathological, clinical and therapeutic aspects. 1791 58

P. falciparum malaria severely affects pregnant women and children. Despite immunity through lifelong exposure to malaria, pregnant women become susceptible to infections causing anaemia, abortions and low birth weight. They experience massive accumulation of infected erythrocytes (IEs) in the placenta. Adhesion of IEs to host endothelial receptors is mediated by members of a large diverse protein family called P. falciparum erythrocyte membrane protein 1 (PfEMP1). Pregnancy malaria is generally associated with the emergence of a distinct subset of parasites expressing a unique PfEMP1 that binds to the host-receptor chondroitin sulfate A (CSA). Resistance to pregnancy malaria is associated with the acquisition of antibodies that block IEs binding to placental CSA. The absence (or rare occurrence) of CSA-binding parasites in malaria patients (children, men and non-pregnant women) suggests that these parasites become virulent only during pregnancy. The molecular mechanisms used by P. falciparum to achieve the timely expression of the Pf-CSA ligand in pregnant women remain puzzling. In this review we will discuss two hypothetical mechanisms by which CSA-binding parasites may arise during pregnancy. The first, a selection process by the placenta of a distinct sub-population of P. falciparum expressing a particular PfEMP1. The second, an induction mechanism that facilitates the expression of a particular PfEMP1 protein by specific host factor(s) present only during pregnancy.
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PMID:Plasmodium falciparum during pregnancy: a puzzling parasite tissue adhesion tropism. 1795 21

Implantation is a complex process involving interactions between the embryo and the uterus. Adhesion, remodeling of the maternal vasculature, and decidualization are crucial events necessary for successful implantation to occur. Heparanase (HPSE), an endo-beta-D-glucuronidase, cleaves heparan sulfate at specific sites, leading to release of growth factors that may be involved in decidualization and remodeling of the maternal vasculature. HPSE also can function as a cell adhesion molecule. The aim of this study was to determine the expression of HPSE in the uteri of nonpregnant and pregnant baboons as well as in human stromal fibroblasts decidualized in vitro. We examined the localization and expression of HPSE using immunohistochemistry, Western blotting, RT-PCR, and activity assays. In nonpregnant baboon uteri, HPSE expression was localized to the apical surface of the glandular epithelia and in glandular secretions. However, in pregnant baboon uteri, HPSE was localized primarily in decidua. Uteri obtained at midpregnancy had higher heparanase activity compared with the nonpregnant uteri. A slight increase in HPSE expression was observed in human stromal fibroblasts decidualized in vitro. HPSE and HPSE2 mRNA transcripts were present in both decidualized tissue and cells. Increases in heparanase activity in the decidua from pregnant baboon uteri compared with tissue from nonpregnant animals and in human stromal fibroblasts decidualized in vitro suggest that HPSE plays a role in extracellular matrix remodeling and in increasing heparin-binding growth factor release during embryo implantation.
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PMID:Decidual heparanase activity is increased during pregnancy in the baboon (Papio anubis) and in in vitro decidualization of human stromal cells. 1798 58

Recent evidence has linked intestinal permeability to mucosal inflammation, but molecular studies are lacking. Candidate regulatory molecules localized within the tight junction (TJ) include Junctional Adhesion Molecule (JAM-A), which has been implicated in the regulation of barrier function and leukocyte migration. Thus, we analyzed the intestinal mucosa of JAM-A-deficient (JAM-A(-/-)) mice for evidence of enhanced permeability and inflammation. Colonic mucosa from JAM-A(-/-) mice had normal epithelial architecture but increased polymorphonuclear leukocyte infiltration and large lymphoid aggregates not seen in wild-type controls. Barrier function experiments revealed increased mucosal permeability, as indicated by enhanced dextran flux, and decreased transepithelial electrical resistance in JAM-A(-/-) mice. The in vivo observations were epithelial specific, because monolayers of JAM-A(-/-) epithelial cells also demonstrated increased permeability. Analyses of other TJ components revealed increased expression of claudin-10 and -15 in the colonic mucosa of JAM-A(-/-) mice and in JAM-A small interfering RNA-treated epithelial cells. Given the observed increase in colonic inflammation and permeability, we assessed the susceptibility of JAM-A(-/-) mice to the induction of colitis with dextran sulfate sodium (DSS). Although DSS-treated JAM-A(-/-) animals had increased clinical disease compared with controls, colonic mucosa showed less injury and increased epithelial proliferation. These findings demonstrate a complex role of JAM-A in intestinal homeostasis by regulating epithelial permeability, inflammation, and proliferation.
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PMID:JAM-A regulates permeability and inflammation in the intestine in vivo. 1803 51


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