Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies raised in rabbits to detergent-solubilized pig kidney microvillar proteins have been used to investigate the membrane hydrolases by crossed immunoelectrophoresis. Eight enzymes were detected by specific staining methods: aminopeptidase M, dipeptidylpeptidase IV, neutral endopeptidase, aminopeptidase A, carboxypeptidase P, gamma-glutamyltransferase, trehalase and phosphodiesterase I. The mobility of all these enzymes, with the exception of trehalase and neutral endopeptidase, was increased by treatment of the detergent-solubilized preparation with papain. The difference between the detergent and proteinase forms of these enzymes is attributed to the removal of a small, non-antigenic peptide to which detergent is bound in significant quantities. This interpretation was further supported by experiments in which the microvillus fraction was labelled with an intramembrane photolabelling reagent, 1-azido-4-[125I]iodobenzene. After photolysis, the radioactivity in the membrane could be solubilized by detergent treatment but not by papain treatment. Radioautography after crossed charge-shift immunoelectrophoresis showed a good correlation between charge-shift (signifying the presence of detergent bound to a hydrophobic domain) and the presence of the label.
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PMID:Proteins of the kidney microvillar membrane. Immunoelectrophoretic analysis of the membrane hydrolases: identification and resolution of the detergent- and proteinase-solubilized forms. 48 90

The ectoenzymes acting in the metabolism of peptides play an essential role in renal cell-cell communication. We have studied four of these ectoenzymes, aminopeptidases N and A (APN, APA), dipeptidylpeptidase IV (DPP IV) and neutral endopeptidase (NEP) in cultured human glomerular mesangial and epithelial cells and cultured rabbit renal cortical vascular smooth muscle cells. APN is present at the surface of both mesangial and epithelial cells with identical characteristics. Its expression (enzyme activity and immunoreactive protein) is induced by phorbol-esters and other protein kinase C-stimulating agents. APA is present only in glomerular epithelial cells. Its expression is induced by glucocorticoids and cyclic AMP-stimulating agents. DPP IV is also present only in glomerular epithelial cells. Its expression (enzyme activity, immunoreactive protein and mRNA) is induced by interferon gamma. NEP is present in glomerular epithelial cells and vascular smooth muscle cells. The expression of the latter enzyme is inhibited in the presence of serum via the combined effect of Ca2+i and PKC-stimulating agents. In contrast, glucocorticoids and cyclic GMP induce its expression. NEP plays a major role in the catabolism by these cells of atrial natriuretic factor. All these data emphasize the multiplicity of the mechanisms controlling ectopeptidase expression in cultured glomerular and renal vascular cells.
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PMID:[Ectoenzymes of peptidic metabolism in renal glomerular and vascular cells]. 133 92

The human colon cancer cell line Caco-2 undergoes spontaneous enterocytic differentiation during growth, and expresses a number of brush-border-membrane-associated hydrolases typical of a differentiated phenotype. Among these are alkaline phosphatase, dipeptidyl peptidase IV and sucrase-isomaltase (sucrase, EC 3.2.1.48). Neutral endopeptidase 24.11 [EC 3.4.24.11, neprilysin (NEP)] is another abundant protease of normal enterocytes but its presence in Caco-2 cells has not been fully documented yet. In this paper, we show that Caco-2 cell extracts hydrolyse tritiated [D-Ala2Leu5]enkephalin with a Km of 180 microM, very close to the value obtained for the NEP present in the rabbit kidney (118 microM). Western-blot analysis of brush-border membranes purified from post-confluent cells revealed a protein with an apparent molecular mass of 94000 Da similar to that of the rabbit kidney NEP. The amount of enzyme in cell extracts increased as a function of the age of the culture, indicating that NEP expression is correlated with the degree of cell differentiation as is also the case for sucrase and dipeptidylpeptidase IV (DPP-IV). Binding of a radiolabelled antibody to Caco-2 cell monolayers grown on semi-permeable filters indicated that 95% of NEP molecules present at the cell surface are on the apical side. Immunocytochemical and flow cytometric analysis of intact and permeabilized cells were also used to investigate the presence of NEP and DPP-IV at the surface of Caco-2 cells. Whereas DPP-IV staining appeared to be homogeneous throughout the entire cell population, NEP-related fluorescence exhibited a bimodal distribution which indicates an uneven expression of the protein at the cell surface. Permeabilization of monolayers with saponin before staining restored a labelling pattern for NEP similar to the one obtained for DPP-IV. This suggests that although DPP-IV and NEP follow similar patterns of expression when enzymic activities are measured on whole-cell extracts, targeting of these brush-border proteins to the cell surface appears to be regulated in different ways.
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PMID:Polarized distribution of neutral endopeptidase 24.11 at the cell surface of cultured human intestinal epithelial Caco-2 cells. 136 26

Immunological abnormalities including lymphocyte subset, lymphocyte immune functional assays, chemical antibodies, and different markers for autoimmune response were examined in individuals exposed to a variety of chemicals in computer manufacturing plants. A comparison of 289 individuals exposed to chemicals to 120 controls revealed that exposed individuals had a significantly higher percentage with either increased or decreased T helper/T suppressor ratios. In addition, the individuals with abnormal T4/T8 ratios demonstrated significant elevation in chemical-hapten antibodies. Therefore, 87 exposed subjects with abnormal T4/T8 ratios were selected for further evaluation by lymphocyte phenotypic expression and T cell, B cell, NK activity, and autoimmune markers, and were compared to 60 controls. The comparison of exposed individuals with controls indicated elevation of T cell (CD3), B cell (CD19), and activated T cell (CD10, CD15, CD26, CD38), suppressed T cell and B cell function decreased or increased NK cell cytotoxic activity. Autoimmunity due to chemical exposure was evidenced by elevation of TA1 phenotype frequencies and presence of rheumatoid factor, immune complexes, ANA, and anti myelin basic protein antibodies. We conclude that chemical exposure may induce immune abnormalities including immune suppression and autoimmunity.
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PMID:Immune alteration associated with exposure to toxic chemicals. 145 35

Using an indirect immunoperoxidase technique, we tested frozen specimens from 12 Wilms' tumors with monoclonal antibodies (MoAbs) reacting against a large panel of molecules including laminin, fibronectin, cytokeratin, vimentin, villin, CD24, CALLA/CD10, CR1, CD26, class I and class II major histocompatibility complex (MHC) molecules, and endothelium factor VIII. These molecules were chosen because they are markers of specific segments of the mature kidney and because their loss or acquisition is indicative of different steps of human nephrogenesis. KI67 MoAb was used to evaluate the proliferating activity of the cells. The blastemal component (cell compact areas) of Wilms' tumors consisted of vimentin-positive cells with a fibronectin network. However, signs of epithelial maturation were present in compact areas where cytokeratin-positive cells producing laminin were observed. The cells exhibited a high degree of proliferating activity. The tubule formations consisted of cytokeratin-positive cells and had a defined laminin border. All the cells, whether in compact areas or in tubules, were strongly CD24-positive. Some tubular formations showed signs of proximal maturation with the presence of CALLA, CD26, and even villin. In four cases class I-MHC molecules were expressed by some tubular cells. Large cystic cavities present in five cases were edged by cytokeratin, CD24-positive cells, or by vimentin, CALLA, CR1-positive cells. Some glomeruloid bodies, present in two cases, were also composed of vimentin, CALLA, and CR1-positive cells which correspond to the mature podocyte phenotype. The interstitial tissue contained mainly laminin and fibronectin network with macrophages and few CD3 lymphocytes. The presence of large cells with muscular differentiation was noted; round vimentin and CD26-positive cells were also seen. The endothelial cells of the vessels exhibited vimentin, factor VIII, and class I and class II MHC molecules as do mature cells, but in some cases the endothelial cells lacked class II molecule expression and were CALLA-positive. These results which confirmed and extended those previously described show that cell differentiation in Wilms' tumor mimics that observed during metanephros development. Moreover, this study shows that tumoral cells in nephroblastoma share several antigens with cells from lymphoid lineage (CD24, CALLA, and CD26) as do developing and mature kidney cells. Such cell phenotype dissection provides a useful and reliable tool for testing the influence of various factors on the development of hetero-transplanted or cultured Wilms' tumors.
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PMID:Cell differentiation in Wilms' tumor (nephroblastoma): an immunohistochemical study. 169 63

The authors tested frozen sections from 28 renal cell carcinomas (RCC)--21 clear, 1 eosinophilic, 4 basophilic, and 2 spindle-shaped cell type--with monoclonal antibodies (MAb) reacting against cytokeratin, vimentin, CD24, CALLA/CD10, villin, CD26, and HLA class I and class II molecules. These molecules are markers of specific segments of the mature kidney, and their loss or acquisition reflects the different steps of human nephrogenesis. KI67 MAb was used to evaluate cell-proliferating activity. All RCC cases expressed cytokeratin. Coexpression of vimentin was observed in 21 of 28 cases. Whether of clear or chromophilic type, all tumoral cells strongly expressed CD24 molecule, present on primitive blastema cells. All clear-type RCCs expressed CALLA/CD10 and 60% were also villin positive; some were faintly positive for CD26. CALLA, villin, and CD26 were not detected in basophilic cell type. HLA class I molecules were variably expressed in almost all cases, but HLA class II were never detected on tumoral cells. Except for the spindle-shaped population, cell-proliferating activity was low. These results favor the hypothesis that RCCs derive from cells that have 'recovered' the different options of metanephric differentiation. Clear cells show evidence of maturation toward proximal type, while basophilic cells do not. It would be of interest to evaluate the usefulness of serum measurements of villin and/or CALLA as markers in clear cell-type RCC.
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PMID:Expression of the human nephron differentiation molecules in renal cell carcinomas. 169 23

The clinical presentation of cervical metastases in a young woman presenting with cervical lymphadenopathy is described. The clinical, histological, ultrastructural and immunological findings establishing the diagnosis of a renal primary tumour are seen. The significance of mixed tumour cell expression of antigens specific for the proximal tubule (CD10, DPP4 and aminopeptidase N) and of Tamm Horsfall protein, normally expressed on the thick ascending limb of loop of Henle and distal tubule, is discussed.
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PMID:Tamm Horsfall protein expression by a small renal cell carcinoma presenting with metastases. 196 77

To analyze the influence of cell differentiation and the effects of hormones on the subcellular distribution of apical antigens in polarized epithelial cells, we have compared the localization of three brush border (BB) hydrolases [neutral endopeptidase (ENDO), aminopeptidase N (APN), and dipeptidylpeptidase IV (DPPIV)] in primary cultures of renal proximal tubule cells grown in various culture media. The degree of cell differentiation modulated by medium composition was estimated by measuring proximal functions, including glucose transport, specific enzymatic activities, and PTH responsiveness. In the dedifferentiated state observed in cells grown in 1% fetal calf serum (FCS)-supplemented medium, the three hydrolases are abnormally concentrated in a cytoplasmic vesicle compartment with weak expression on both membrane domains. By contrast, in serum-free hormonally defined medium (DM: insulin, 5 microgram/ml; dexamethasone, 5 x 10(-8) M), which markedly enhances morphological and functional cell differentiation, the distribution of hydrolases parallels that observed in the normal tubule. When added to the DM devoid of hormones, insulin has little polarizing effect, whereas dexamethasone dramatically increases the apical expression of the hydrolases, which then almost disappear from the basolateral membrane and cytoplasmic vesicular compartments. This glucocorticoid hormone augments the amount of immunoreactive antigen detectable on the apical domain in paraformaldehyde-fixed cells but does not change the total enzymatic activity. This suggests the presence in tubular cells of a dexamethasone-dependent polarizing machinery that requires de novo RNA and protein synthesis, and probably acts mainly by targeting a storage cytoplasmic pool of enzyme to the apical domain.
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PMID:Polarized membrane expression of brush-border hydrolases in primary cultures of kidney proximal tubular cells depends on cell differentiation and is induced by dexamethasone. 197 36

We previously characterized a dimeric, Mr = 115,000, developmentally regulated mouse T cell-activating molecule (THAM). We show in this report that the THAM-specific mAb H194-112 exhibits strong reactivity with several nonlymphoid tissues including polarized enterocytes from small intestine, kidney cortical tubuli, and liver bile ductuli, as well as kidney glomeruli and lung alveoloar pneumocytes. Both the tissue distribution and the structural features of THAM made it likely that this molecule belongs to the ectoenzyme family. This was confirmed by the following experimental evidence: 1) the H194-112+ molecules from enterocyte brush borders (BB) or M14.T thymoma cells were recognized by several antisera specific for intestinal aminopeptidase N (AP-N); 2) mAb H194-112 was found to immunodeplete the AP-N activity from both thymic or enterocyte BB detergent extracts; 3) the hydrophilic, Mr = 115,000 form obtained by papain treatment of thymoma or enterocyte BB could be immunopurified on H194-112 column and exhibited, after hypotonic elution, strong enzymatic activity on the AP-N substrates (i.e., leucyl or alanyl beta-derivatives); 4) mAb H194-112 was found to inhibit the AP-N activity when assayed on alanyl but not leucyl beta-naphthylamide substrate; and 5) preincubation of AP-N with mAb H194-112 prevented the inhibiting effects of bestatin and D,L-methionyl hydroxamate on AP-N activity. These data add a new member to the list of functional ectoenzymatic markers of lymphoid cells (i.e., CD10, CD13, CD26, CD55, and CD73). In view of the known immunomodulating properties of bestatin, one may speculate that the T cell-activating effects of mAb H194-112 is related to an impairment of a surface enzymatic function regulating lymphoid cell activation.
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PMID:Characterization of the neutral aminopeptidase activity associated to the mouse thymocyte-activating molecule. 218 10

Some of the many cell-surface antigens defined by the CD (cluster differentiation) nomenclature have lately emerged as proteins with well-characterised enzymic activities. One important example is CD10 or CALLA (common acute lymphoblastic leukaemia antigen), which is identical to endopeptidase-24.11, an enzyme with an important role in the hydrolysis of biologically active peptides. CD13 and CD26 are also surface peptidases. These enzymes, which have a wide distribution on the surfaces of various cell types, may have specific roles in the control of growth and differentiation in both haemopoietic and epithelial cell systems.
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PMID:Cell-surface peptidases as modulators of growth and differentiation. 257 Oct 20


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