Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous investigations established that focal subretinal injections of neuraminidase, chondroitinase, and hyaluronidase in the rabbit lead to a diffuse loss of retinal adhesiveness beyond the site of injection. This loss of adhesiveness, measured by peeling of the retina immediately after enucleation, correlates with changes in the interphotoreceptor matrix (IPM), as monitored by lectin histochemistry. In this study, rabbits were evaluated during recovery of retinal adhesiveness after subretinal injections of neuraminidase and chondroitinase. Adhesion recovered steadily 5-20 days after chondroitinase injection. After administration of neuraminidase, adhesion remained low for approximately 14 days but recovered to normal by 20 days. The recovery of adhesiveness correlated closely with reestablishment of the normal distribution of peanut agglutinin-binding glycoconjugates in the IPM, one group of molecules thought to participate in retinal adhesion. Electroretinography and light microscopy showed no abnormalities in the retina or retinal pigment epithelium after recovery. These results suggest that IPM glycoconjugates participate in maintaining retinal adhesion.
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PMID:Recovery of retinal adhesion after enzymatic perturbation of the interphotoreceptor matrix. 154 77

Asthma is a disease of airway inflammation and hyperreactivity that is associated with a lymphocytic infiltrate in the bronchial submucosa. The interactions between infiltrating T lymphocytes with cellular and extracellular matrix components of the airway and the consequences of these interactions have not been defined. We demonstrate the constitutive expression of CD44 on human airway smooth muscle (ASM) cells in culture as well as in human bronchial tissue transplanted into severe combined immunodeficient mice. In contrast, basal levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression are minimal but are induced on ASM by inflammatory mediators such as tumor necrosis factor alpha (TNF-alpha). Activated, but not resting T cells, adhere to cultured ASM; stimulation of the ASM with TNF-alpha enhanced this adhesion. Adhesion was partially blocked by monoclonal antibodies (mAb) specific for lymphocyte function-associated antigen 1 (LFA-1) and very late antigen 4 (VLA-4) on T cells and ICAM-1 and VCAM-1 on ASM cells. The observed integrin-independent adhesion was mediated by CD44/hyaluronate interactions as it was inhibited by anti-CD44 mAb 5F12 and by hyaluronidase. Furthermore, the adhesion of activated T lymphocytes induced DNA synthesis in growth-arrested ASM cells. Thus, the interaction between T cells and ASM may provide insight into the mechanisms that induce bronchial inflammation and possibly ASM cell hyperplasia seen in asthma.
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PMID:T lymphocytes adhere to airway smooth muscle cells via integrins and CD44 and induce smooth muscle cell DNA synthesis. 752 Apr 73

Our previous studies have suggested that the interaction between hyaluronic acid (HA) on peritoneal mesothelial cells and the membrane adhesion molecule, CD44, on ovarian tumour cells could be important in ovarian cancer metastasis. In order to study this further, adhesion of six ovarian tumour lines to HA coated on to a plastic surface was investigated. Four lines bound to the HA coat and two lines did not. The adhesive lines were those that expressed high amounts of CD44, but the degree of adhesion was not closely correlated with CD44 expression. The results suggested that different tumour lines had different affinities for HA. Treatment of the HA coat with hyaluronidase substantially reduced adhesion. Adhesion was also partially reduced if the tumour cells were preincubated with either soluble HA, or anti-CD44 antibodies directed against the HA binding region. An antibody against a non-HA binding region only slightly blocked adhesion at high antibody concentrations. Only the CD44H isoform was detected by immunoprecipitation on the tumour cells. These results suggest that ovarian tumour cells can attach to immobilised HA via CD44H on the cell membrane.
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PMID:Human ovarian tumour cells can bind hyaluronic acid via membrane CD44: a possible step in peritoneal metastasis. 887 6

Adhesion and migration of mouse fetal liver (FL) cells to the thymus were investigated using cells from green fluorescent protein transgenic (GFP+) mice. FL cells from GFP+ embryos at 12 gestational days (E12) of mice were incubated with 2'-deoxyguanosine-treated fetal thymus lobe (from E14) by thymic repopulation (hanging drop) culture methods. GFP+ cells were observed in the thymus lobe at the end of the repopulation culture period. A large part of the infiltrated cells expressed CD44 until day 2 of culture on a permeable membrane, then lost the expression. CD25 expression was observed from day 1 to day 4. Around day 8, GFP+ cells became both CD4+ and CD8+. The results support the early observation of the sequential expression of CD44, CD25, and CD4/8 during the early stages of thymocyte development. When anti-CD44 mAb was added at the beginning of the repopulation culture period, GFP+ FL cells adhered to the surface of the thymus lobe but did not migrate into the thymus. Pretreatment of the thymus with hyaluronidase or hyaluronate produced results similar to the results of anti-CD44 treatment. On the other hand, the addition of anti-integrin alpha4 mAb inhibited adhesion to the thymus, and almost no GFP+ cells were seen on the surface of the thymus lobe. The data suggest that integrin alpha4 and CD44 play different roles, i.e., integrin alpha4 is required for the adhesion of FL cells to the thymus lobe and CD44 is required for the migration of the cells into the thymus.
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PMID:Roles of integrins and CD44 on the adhesion and migration of fetal liver cells to the fetal thymus. 1047 89

Pathological changes in inflammatory bowel disease include an increase in intestinal mucosal mononuclear leukocytes and hyperplasia of the muscularis mucosae smooth muscle cells (M-SMCs). Because virus infections have correlated with disease flare, we tested the response of cultured M-SMCs to respiratory syncytial virus, measles virus, and the viral analogue, poly(I.C). Adhesion of U937 cells and peripheral blood mononuclear cells was used to measure the leukocyte-interactive potential of M-SMCs. Untreated M-SMCs, only minimally adhesive for leukocytes, bound U937 cells after treatment with respiratory syncytial virus or measles virus. Mononuclear leukocytes also bound to poly(I.C)-treated M-SMCs. Although both vascular cell adhesion molecule-1 mRNA and protein increased 3-4-fold in poly(I.C)-treated M-SMC cultures, U937 cell adhesion was not blocked by an anti-vascular cell adhesion molecule-1 monoclonal antibody. However, hyaluronidase digestion of poly(I.C)- or virus-treated M-SMCs dramatically reduced leukocyte adhesion ( approximately 75%). Fluorophore-assisted carbohydrate electrophoresis demonstrated a approximately 3-fold increase in surface-bound hyaluronan on poly(I.C)-treated M-SMCs compared with untreated controls. In addition, pretreatment of mononuclear cells with a blocking anti-CD44 antibody, greatly decreased adhesion to poly(I.C)-treated M-SMCs. Recognition of this virus-induced hyaluronan/CD44 mechanism of mesenchymal cell/leukocyte interaction introduces a new avenue in the research of gut inflammation.
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PMID:Mononuclear leukocytes preferentially bind via CD44 to hyaluronan on human intestinal mucosal smooth muscle cells after virus infection or treatment with poly(I.C). 1052 64

In mice bearing the Rb(6.16) or Rb(6.15) Robertsonian translocation (Rb), sperm dysfunction associated with the Rbs has been shown to lead to transmission ratio distortions (TRDs) in heterozygotes. The severity of the TRDs is directly related to the severity in the alteration of expression of the gene for the Sperm Adhesion Molecule 1 (Spam1), which maps to proximal mouse Chromosome 6 (Chr 6) near the translocation junction and encodes a sperm antigen with hyaluronidase activity. Here we demonstrate that there is a significantly reduced fertility in the Rb homozygotes (P < 0.001), based on litter size; and that with the Sperm Select Penetration assay Rb-bearing sperm have significantly decreased (P < 0.02-0.001) rates of penetration of hyaluronic acid. Catalytic kinetics studies indicate that reduced Spam1 (PH-20) hyaluronidase activity in the Rb(6.15) mice results from a qualitative defect, while for Rb(6.16) with the greater TRD both a qualitative and a quantitative deficiency (confirmed by Western analysis) of Spam1 exist. Six point mutations were shown to be clustered in the Spam1 hyaluronic acid-binding domain in Rb(6.15). For Rb(6.16) which has a gross genomic alteration at the Spam1 locus, 11 point mutations are scattered in the 5' and 3' UTRs and the coding region, where one leads to the replacement of a conserved residue. Entrapment of spontaneous Spam1 mutations, owing to recombination suppression near the Rb junctions, is proposed as the major underlying defect of the sperm dysfunction.
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PMID:Spam1 (PH-20) mutations and sperm dysfunction in mice with the Rb(6.16) or Rb(6.15) translocation. 1184 84

Rat sperm surface antigen Sperm Adhesion Molecule1, SPAM1 (a.k.a. 2B1 or PH-20) is a plasma membrane-bound glycoprotein with hyaluronidase activity and putative roles during fertilization. Previously the antigen was thought to be testis-specific but recently it has been shown to be synthesized in the epididymis (mouse, macaque and human). Using the efferent ductule ligated (EDL) rat as a model to produce a sperm-free androgen-maintained epididymis, we have examined the factors regulating the expression of epididymal 2B1. RT-PCR and in situ transcript hybridization (ISH) studies showed that 2B1 mRNA is transcribed in the principal cells in all three regions of the epididymis. Its cognate protein was also detected by Western blot analysis in sperm-free cytosols from normal epididymis and found to undergo endoproteolytic cleavage into 2 subunits of similar size to the sperm-bound form. Immunohistochemistry with a monoclonal antibody to 2B1 confirmed that the protein is present in the epididymal epithelium and luminal secretions. The intensity of staining was much stronger in the sperm-free EDL epididymis than that in the normal (sperm-present) epididymis. The protein was shown to have hyaluronidase activity at neutral pH and both its quantity and activity appeared to be greater in the EDL epididymis. It is suggested that a soluble form of SPAM1 glycoprotein is synthesized and released in the epididymis and that in addition to androgens, its regulation may involve a cross-talk between the tubule epithelium and lumicrine factors, the latter possibly of testicular origin.
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PMID:Expression and secretion of rat SPAM1(2B1 or PH-20) in the epididymis: role of testicular lumicrine factors. 1506 58

The Sperm Adhesion Molecule1 (SPAM1) is the most widely conserved sperm antigen with important roles in mammalian fertilization. Light and electron microscopy were used to localize, by in situ hybridization, the cellular and subcellular sites of Spam1 mRNA in the murine testis. Transcripts were first detected in step 3 round spermatids, gradually increased until step 8 and abruptly decreased between steps 9-11. They were predominantly localized near the ER and were not dispersed throughout the cytoplasm. Immunohistochemistry revealed that Spam1 is present on both the head and tail of sperm in the seminiferous tubules, and provided support for transcriptional regulation of its transcript. Immunocytochemistry confirmed the location of Spam1 on the tail of testicular sperm and demonstrated that it is localized to both the principal piece and the midpiece. Spam1 on epididymal sperm is localized to the midpiece of the tail and changes from a uniform distribution on the head in the caput to a regionalized pattern, first on the posterior and then on the anterior head, in caudal sperm. Spam1 on the surface of caudal sperm was shown to mediate the increase in acrosome reactions induced by the synergistic effects of HA and progesterone, as confirmed in sperm from the Rb(6.16) translocation-bearing mice which are Spam1 mutants. The similar response of human and mouse sperm to these agonists of the acrosome reaction, underscores the usefulness of the mouse as a model to study physiological aspects of SPAM1 in humans where, unlike the mouse, it is the only sperm hyaluronidase.
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PMID:Cytoplasmic localization during testicular biogenesis of the murine mRNA for Spam1 (PH-20), a protein involved in acrosomal exocytosis. 1545 44

The relation between adherence of Escherichia coli and expression of mucin-1 (Muc1: an integral membrane mucin) mRNA in the endometrium was studied in beagle bitches at different stages of the oestrous cycle and in those with cystic endometrial hyperplasia/pyometra complex (pyometra). The number of E. coli adhering to the endometrium was low at pro-oestrus and oestrus and increased at the early stage (day 10) of dioestrus, corresponding to the implantation period; it declined thereafter. Adhesion of the organisms to endometrial epithelial cells collected at day 10 of dioestrus was inhibited by the addition of D-mannose. When endometrial epithelial cells collected at pro-oestrus were treated with hyaluronidase, an enzyme that digests mucins, the numbers of E. coli adhering to the cells tended to increase. With polymerase chain reaction analysis it was possible to detect Muc1 gene transcripts in the endometrium at all stages of the oestrous cycle, although the level of Muc1 mRNA decreased by day 10 of dioestrus. The levels of Muc1 mRNA in bitches with a clinical stage of pyometra were low and comparable to those at day 10 of dioestrus. The number of E. coli adhering to the endometrium and Muc1 mRNA levels in the endometrium were inversely correlated (r=-0.77, P<0.01). Immunohistochemical analysis showed little staining for Muc1 in the endometrial epithelia at day 10 of dioestrus and in bitches with pyometra. These results suggest that reduction of Muc1 expression is associated with increased E. coli adherence in the canine uterus at the early stage of dioestrus, possibly facilitating the development of pyometra.
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PMID:Reduction of mucin-1 gene expression associated with increased Escherichia coli adherence in the canine uterus in the early stage of dioestrus. 1641 13

Prostate cancer progression can be predicted in human tumor biopsies by abundant hyaluronan (HA) and its processing enzyme, the hyaluronidase HYAL1. Accumulation of HA is dictated by the balance between expression levels of HA synthases, the enzymes that produce HA polymers, and hyaluronidases, which process polymers to oligosaccharides. Aggressive prostate tumor cells express 20-fold higher levels of the hyaluronan synthase HAS3, but the mechanistic relevance of this correlation has not been determined. We stably overexpressed HAS3 in prostate tumor cells. Adhesion to extracellular matrix and cellular growth kinetics in vitro were significantly reduced. Slow growth in culture was restored either by exogenous addition of hyaluronidase or by stable HYAL1 coexpression. Coexpression did not improve comparably slow growth in mice, however, suggesting that excess hyaluronan production by HAS3 may alter the balance required for induced tumor growth. To address this, we used a tetracycline-inducible HAS3 expression system in which hyaluronan production could be experimentally controlled. Adjusting temporal parameters of hyaluronan production directly affected growth rate of the cells. Relief from growth suppression in vitro but not in vivo by enzymatic removal of HA effectively uncoupled the respective roles of hyaluronan in growth and angiogenesis, suggesting that growth mediation is less critical to establishment of the tumor than early vascular development. Collectively results also imply that HA processing by elevated HYAL1 expression in invasive prostate cancer is a requirement for progression.
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PMID:Inducible hyaluronan production reveals differential effects on prostate tumor cell growth and tumor angiogenesis. 1750 71


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