Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human foetal liver cells are an enriched source of mast cell progenitors that complete their differentiation and mature in response to stem cell factor, the ligand for Kit, in liquid culture. These mast cells are Kit+, metachromatic with toluidine blue+, tryptase+, histamine+ and show ultrastructure features of mast cells. Using a panel of monoclonal antibodies (mAb) against different cell-surface antigens (33 mAb were used), the cell-surface phenotype of human stem cell factor-dependent foetal liver-derived mast cells was examined by flow cytometry. Consistent with previous reports on tissue-derived mast cells, those derived from foetal liver in vitro expressed HLA class I, CD9, CD29, CD33, CD43, CD45 and Kit. Unlike mast cells dispersed from tissue, a high expression of CD13 was found. Also, these in vitro-derived mast cells express little, if any, high-affinity IgE receptor. However, small amounts of mRNA for the alpha-chain in foetal liver-derived mast cells compared to KU812 cells (a human basophil-like cell line) could be detected by Northern blotting. Full expression of Fc epsilon RI may require additional growth factor(s).
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PMID:Phenotypic characterization of stem cell factor-dependent human foetal liver-derived mast cells. 768 44

Opioid peptides are converted by mushroom tyrosinase into melanin-like compounds retaining the peptide moiety (opio-melanins). Opio-melanins, owing to the presence of the linked aminoacids and in contrast with DOPA-melanin, are soluble compounds. The enkephalin-generated melanins are cleaved by carboxypeptidase A and pronase whereas aminopeptidase M cannot remove aminoacids from the pigment. Enkephalins, as well as other opioid peptides, (alpha-endorphin, kyotorphin, esorphins) if oxidized in presence of DOPA and tyrosinase are readily incorporated into DOPA-melanin. The resulting mixed-melanins (opio-melanin + DOPA-melanin) can be solubilized in hydrophilic solvents. Melanin from leu-enkephalin exhibits paramagnetism as evidenced by an EPR spectrum identical to that of DOPA-melanin, but unlike the latter pigment, it does not appear to oxidize NADH, probably for the presence of the peptide moiety that exerts a hampering effect on the oxidizing capacity.
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PMID:Some biochemical properties of melanins from opioid peptides. 790 28

We have established the peptidase content of a P2 fraction (enriched in synaptosomes) and plasma membranes prepared from canine intestinal mucosa. Fourteen exo- and endopeptidases were assayed with fluorimetric or chromogenic substrates and identified by means of specific peptidase inhibitors. Post-proline dipeptidyl aminopeptidase IV, aminopeptidase M, and carboxypeptidase A were the most abundant exopeptidases, while aminopeptidases A and B, dipeptidyl aminopeptidase, pyroglutamyl peptide hydrolase I, and carboxypeptidase B displayed little, if any, activity. Endopeptidase 24.11 was the only endopeptidase that was detected in high amount. By contrast, proline endopeptidase exhibited a low activity, while angiotensin-converting enzyme, endopeptidase 24.15, endopeptidase 24.16, and cathepsin B and D-like activities were not detected. The catabolic rates of the two related neuropeptides, neurotensin (NT) and neuromedin N (NN), established that NN was inactivated 16 to 24 times faster than NT by plasma membrane and P2 fractions, respectively. Furthermore, the two peptides underwent qualitatively distinct mechanisms of degradation. A phosphoramidon-sensitive formation of NT(1-10) was detected as the major NT catabolite, indicating that NT was susceptible to an endoproteolytic cleavage elicited by endopeptidase 24.11. By contrast, NN was inactivated by the action of an exopeptidase at its N-terminus, leading to the formation of [des-Lys1]NN. The occurrence of this NN metabolite was prevented by bestatin and actinonin, but not by the aminopeptidase B inhibitor, arphamenine B, indicating that the release of the N-terminal residue of NN was likely due to aminopeptidase M.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential catabolic fate of neuromedin N and neurotensin in the canine intestinal mucosa. 833 46

LAMA-84, a human leucocytic cell line, which upon establishment was described as having megakaryocytic, erythroid and granulocytic characteristics, was analysed for expression of various differentiation markers. In addition to some of the previously described phenotypic characteristics, this cell line was found to express mRNA for several proteins characteristic for basophilic leucocytes and mast cells. The authors show that LAMA-84 cells express mRNA for the mast cell tryptase, the proteoglycan core protein, carboxypeptidase A and the alpha and beta chains of the high affinity IgE receptor (Fc epsilon RI). The authors examined the potential of LAMA-84 to differentiate in serum-free medium or after DMSO or PMA treatment. Depending on the inducing factor, surface expression of the Fc epsilon RI alpha-chain was increased from 20% to 35-50% of the cells and mRNA levels for tryptase were increased in serum-free medium and after DMSO treatment. LAMA-84 was found to express CD13, CDw17, CD29, CD33, CD40, CD45 and CD117. Furthermore, mRNA for the eosinophil/basophil markers Charcot-Leyden crystal (CLC) protein and the major basic protein (MBP), as well as the erythrocyte differentiation marker alpha-globin, was detected. However, the authors observed only trace amounts of mRNA for another erythroid differentiation marker (glycophorin), trace amounts of the megakaryocytic marker GPIIIa, and no detectable level of GPIb alpha. By comparing the expression pattern of a panel of differentiation markers in LAMA-84, and a second human cell line (KU812) expressing a basophil phenotype, it is evident that these cell lines, which presently are the only two cell lines identified with basophilic characteristics, share a large number of phenotypic characteristics.
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PMID:Characterization of a human basophil-like cell line (LAMA-84). 869 92

pl6l is a membrane glycoprotein expressed on mast cells and on activated macrophages but on few if any other cells of hematopoietic lineages. Its lack of expression on basophils makes it useful to distinguish mast cells from basophils and aids in the analysis of mast cells and their precursors. p161 was purified from the mast cell line CFTL-12 by affinity chromatography and subjected to limited proteolysis. The sequences of the resultant peptides indicated that p161 is homologous with rat and human CD13/aminopeptidase N. Using oligonucleotide primers derived from rat CD13 cDNA, a mouse cDNA was obtained. Its deduced amino acid sequence displays 87% identity with rat CD13 and 76 % identity with human CD13. Expression of the mouse cDNA in M12 cells, which are p161 negative, renders these cells positive for staining with the monoclonal anti-p161 Ab, K-1. Furthermore, a mAb raised against partially purified mouse intestinal aminopeptidase N specifically blocked the binding of K-1 to both CFTL-12 cells and the transfected M12 cells. These results strongly indicate that mouse p161 is CD13/aminopeptidase N. Northern blot analysis shows that p161 mRNA is most abundantly expressed in the intestinal tract and kidney and is present in liver, lymph node, spleen, and brain.
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PMID:p161, a murine membrane protein expressed on mast cells and some macrophages, is mouse CD13/aminopeptidase N. 880 62

The intestinal enzymatic degradation of the immunomodulating peptides thymotrinan (TP3), thymocartin (TP4), and thymopentin (TP5), three oligopeptides derived from the naturally occurring thymus hormone thymopoietin, was investigated to evaluate their potential for peroral drug delivery. In the presence of brush-border membrane vesicles, crude pancreas extract and everted rings from duodenum, jejunum, ileum, and colon, all peptides were shown to be degraded both by pancreatic enzymes and brush-border aminopeptidases. Degradation clearances (Cldeg) of TP3, TP4, and TP5 were calculated for a quantitative comparison of peptide stability. In the presence of crude pancreas extract, there was a rapid degradation of TP5 (Cldeg 17.9 ml/min) in comparison with TP3 and TP4 (Cldeg 0.95 and 0.56 ml/min, respectively, at 0.2 mM peptide concentration) caused by the cleavage of the C-terminal tyrosine by carboxypeptidase A, whereas TP3 and TP4 underwent hydrolysis by aminopeptidase N. In the presence of brush-border membrane vesicles, the degradation clearances were 3.9, 3.1, and 2.4 ml/min at 0.2 mM concentrations of TP4, TP5, and TP3, respectively. The clearance of all peptides was lowered with increasing peptide concentrations, indicating saturable degradation processes. The degradation of the thymopoietin oligopeptides in the presence of brush-border membrane enzymes was exclusively catalyzed by aminopeptidase N. The degradation of all peptides was highly dependent on the intestinal segment, with the lowest degradation clearance observed in the colon.
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PMID:Enzymatic cleavage of thymopoietin oligopeptides by pancreatic and intestinal brush-border enzymes. 895 40

The immunophenotypic characteristics of both bone marrow (BM) and peripheral blood (PB) mast cells (MC), from a patient suffering from an aggressive systemic mast cell disease (SMCD), were sequentially analyzed by flow cytometry using direct immunofluorescence. Analysis was carried out at diagnosis, during clinical response induced by interferon alfa-2h/prednisone therapy, and later at relapse. Our results show that together with the CD117 and IgE characteristic markers, at diagnosis BM MC showed strong expression of CD11c, CD13, CD29, CD33, CD44, CD45, CD63, and CD71, and they were also positive for CD2, CD22, CD25, and CD54 although at a lower level. PB MC displayed similar immunophenotypic characteristics although they had a lower expression of CD11c, CD25, CD33, CD63, CD69, and CD71 with a higher reactivity for CD117. Unlike BM MC, PB MC were weakly positive for CD41a and CD61. Sequential studies showed decreased numbers of both BM and PB MC during clinical response associated with a higher expression of the CD29 and CD54 adhesion molecules. In turn, clinical relapse was related to increased numbers of PB and BM MC together with lower CD2, CD11c, CD45, and and CD54 expression and a higher reactivity for the CD117 and CD25 antigens. CD2 had become negative at the last follow-up study. In addition, an increased proportion of S-phase MC was observed at relapse. These findings suggest that the assessment of the quantitative expression of cell-adhesion molecules and growth-factor receptors together with cell cycle studies of mast cells could be of value for monitoring therapy and predicting clinical outcome in aggressive SMCD.
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PMID:Sequential immunophenotypic analysis of mast cells in a case of systemic mast cell disease evolving to a mast cell leukemia. 914 16

We have been developing a novel bioadhesive drug-carrier matrix that protects embedded therapeutic peptides and proteins from degradation by the most abundant intestinal proteases. Increasing amounts of the Bowman-Birk inhibitor (BBI) were thereby covalently linked to chitosan-EDTA. The bioadhesive properties of the resulting polymer-BBI conjugates and their inhibitory effect toward trypsin (EC 3.4.21.4), chymotrypsin (EC 3.4.21.1), elastase (3.4.21.36), carboxypeptidase A (EC 3.4.17.1), and aminopeptidase N (EC 3.4.11.2) were evaluated in vitro. Whereas unmodified chitosan-EDTA exhibited under our experimental conditions an adhesive strength of 54.4 +/- 7.7 mN, it was determined to be 21.0 +/- 3.8 mN for the comparably most adhesive polymer-BBI conjugate (mean +/- SD; n = 5). All polymer-BBI conjugates showed a strong inhibitory activity toward the serine proteases trypsin and chymotrypsin. However, the protective effect toward elastase was markedly lower. Due to the high binding affinity of chitosan-EDTA toward zinc, which represents an essential cofactor for carboxypeptidase A and aminopeptidase N, all polymer-BBI conjugates displayed additionally a strong protective effect toward these exopeptidases. The novel bioadhesive polymer-BBI conjugates described in this study seem to be very useful drug-carrier matrixes in overcoming the enzymatic barrier to orally administered peptide and protein drugs.
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PMID:Intestinal peptide and protein delivery: novel bioadhesive drug-carrier matrix shielding from enzymatic attack. 954 94

The purpose of the present study was to synthesize and evaluate mucoadhesive polymers, exhibiting a high capacity to bind bivalent cations which are essential co-factors for intestinal proteolytic enzymes. Under the formation of amide bonds, the complexing agent EDTA was covalently bound to the primary amino groups of chitosan. One gram of the resulting conjugate with the lowest amount of remaining free amino groups (0.1 +/- 0.03%; mean +/- SD, n = 3) based on free chitosan as 1.0 was capable of binding 1.4 +/- 0.1 mM calcium, 2.0 +/- 0.1 mM zinc and 1.9 +/- 0.03 mM cobalt (mean +/- SD, n = 3) under intestinal pH-conditions, respectively. Whereas proteolytic activity of the serine proteases trypsin (EC 3.4.21.4), alpha-chymotrypsin (EC 3.4.21.1) and elastase (EC 3.4.21.36) could not be inhibited, proteolytic activity of the zinc proteases carboxypeptidase A (EC 3.4.17.1) and aminopeptidase N (EC 3.4.11.2) was strongly inhibited by the chitosan-EDTA conjugate. Moreover, it displays quick swelling properties in water and basic aqueous solutions. The adhesive force of the conjugate was even higher than of chitosan HCl. However, lowering the percentage of covalently attached EDTA on the polymer, leads to a significantly reduced adhesive force. According to these results, chitosan-EDTA conjugates exhibiting the lowest amount of remaining free amino groups, seem to be a useful tool in overcoming the enzymatic barrier for perorally administered therapeutic peptides.
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PMID:Mucoadhesive polymers as platforms for peroral peptide delivery and absorption: synthesis and evaluation of different chitosan-EDTA conjugates. 968 88

Flavonoids and other benzopyrone substances, having an appropriate hydroxylation profile, may inhibit the metalloenzymes leucine aminopeptidase (LAP), aminopeptidase M (AP-M), and carboxypeptidase A (CP-A). A structural feature that evidently favours the interaction between flavonoids and the three metalloenzymes is the 2,3-double bond conjugating the A and B rings and conferring a planar structure. This can be considered virtually indispensable for inhibition of the three metallopeptidases, though the hydroxylation profile required differed for each of the enzymes, and the interaction mechanism and behaviour also differed. The inhibitory effect of flavonoids on LAP was reversible, and to be effective the flavonoid had to have conjugated A and B rings and ortho-dihydroxylation on at least one of the aromatic rings. This same requirement was essential for inhibition by coumarins and was attributed to a catechol-like mechanism of interaction. The inhibitory effects on AP-M were due to inactivation of the enzyme, irreversibly altered by flavonoids with a 2,3-double bond and a minimum of one hydroxyl substituent on each of the aromatic rings. With CP-A, conjugation of the A and B rings enhanced the inhibitory effect of flavonoids, though it was not strictly required. The interaction between the polyphenolic substances tested and the two zinc aminopeptidases was not reversed by adding zinc to the reaction medium, indicating that the inhibition is not due to the coordination of the phenolic hydroxyl groups with the catalytical zinc of active site, though the presence of zinc affected the interaction behaviour differently according to each substance's hydroxylation profile.
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PMID:Inhibition of zinc metallopeptidases by flavonoids and related phenolic compounds: structure-activity relationships. 979 38


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