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

We provide convergent and multiple evidence for a CD26/CXCR4 interaction. Thus, CD26 codistributes with CXCR4, and both coimmunoprecipitate from membranes of T (CD4(+)) and B (CD4(-)) cell lines. Upon induction with stromal cell-derived factor 1alpha (SDF-1alpha), CD26 is cointernalized with CXCR4. CXCR4-mediated down-regulation of CD26 is not induced by antagonists or human immunodeficiency virus (HIV)-1 gp120. SDF-1alpha-mediated down-regulation of CD26 is not blocked by pertussis toxin but does not occur in cells expressing mutant CXCR4 receptors unable to internalize. Codistribution and cointernalization also occurs in peripheral blood lymphocytes. Since CD26 is a cell surface endopeptidase that has the capacity to cleave SDF-1alpha, the CXCR4.CD26 complex is likely a functional unit in which CD26 may directly modulate SDF-1alpha-induced chemotaxis and antiviral capacity. CD26 anchors adenosine deaminase (ADA) to the lymphocyte cell surface, and this interaction is blocked by HIV-1 gp120. Here we demonstrate that gp120 interacts with CD26 and that gp120-mediated disruption of ADA/CD26 interaction is a consequence of a first interaction of gp120 with a domain different from the ADA binding site. SDF-1alpha and gp120 induce the appearance of pseudopodia in which CD26 and CXCR4 colocalize and in which ADA is not present. The physical association of CXCR4 and CD26, direct or part of a supramolecular structure, suggests a role on the function of the immune system and the pathophysiology of HIV infection.
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PMID:Comodulation of CXCR4 and CD26 in human lymphocytes. 1127 78

Caco-2 is a colonic tumour cell line which, when cultured, spontaneously exhibits enterocyte-like characteristics. Given the difficulties in maintaining long-lasting cultures of enterocytes, this cell line may be a suitable in vitro model to carry out experiments trying to delineate the involvement of enterocytes in local immune responses, and their role in pathology. It seems then reasonable to obtain a detailed immune analysis of Caco-2, and compare it with available data on enterocytes. Cytofluorometry revealed several leukocyte markers on Caco-2, present also on human enterocytes. These markers include surface proteases (CD10, CD13 and CD26), antigen-presenting cell markers (CD13, CD14, CD35 and CD63), integrins (CD18 and CD61), epithelial/endothelial markers (CD21, CD31, CD47 and CD59) and finally, CD25 and CD28. In contrast to enterocytes, HLA-class 11 molecules are not found on Caco-2, whether resting or gamma-IFN-stimulated. Moreover, culture experiments with allogeneic lymphocytes revealed that Caco-2 cells were unable to induce their proliferation. Cytokine analysis showed an increased RANTES synthesis and IL-2 transcription upon stimulation with IL-1beta. Finally, amongst RANTES receptors, CCR1 is found on Caco-2 cells, whereas CCR3 and CCR5 are not.
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PMID:Cell surface phenotype and cytokine secretion in Caco-2 cell cultures: increased RANTES production and IL-2 transcription upon stimulation with IL-1beta. 1182 1

In this study we examined surface expression of CD26 and the corresponding enzyme activity of dipeptidyl peptidase IV (DPPIV) on the cells of immature murine T-cell line, R1.1. The data obtained have shown that R1.1 cells express high density of surface CD26 as compared to normal thymus cells. This was associated with strong enzyme activity, which, based on substrates and inhibitor specificity, corresponded to DPPIV. The DPPIV enzyme activity of R1.1 cells was 10 times stronger than that found on normal murine thymus cells (V(max) = 39 micromol/min/10(6) cells, vs 3.7 micromol/min/10(6) cells, respectively). Upon activation with anti-CD3, up-regulation of both membrane CD26, as well as of DPPIV enzyme activity on R1.1 cells were observed. The finding of strong DPPIV on R1.1 cells makes them suitable model for testing putative substrates/inhibitors of the enzyme in its natural microenvironment. Since in addition to strong DPPIV, R1.1 cells also express kappa opioid receptors (KOR) [European Journal of Pharmacology 227 (1992) 257], we tested the effect of dynorphin-A(1-17), an endogenous opioid peptide with KOR selectivity, on DPPIV of R1.1 cells. Dynorphin-A(1-17) down-regulated DPPIV in a dose-dependent manner, with the potency similar to that of substance P, a known natural DPPIV substrate [Journal of Pharmacology and Experimental Therapeutics 260 (1992) 1257]. DPPIV down-regulation was resistant to bestatin and thiorphan, the inhibitors of two cell surface peptidases (APN and NEP, respectively) with potential of dynorphin-A(1-17) degradation, suggesting that the mechanism underlying the observed effect does not involve degradative products of dynorphin-A(1-17). DPPIV down-regulation was also resistent to KOR antagonist, NBI, suggesting that the mechanism underlying the observed phenomenon involves neither cointernalization of KOR and DPPIV. Collectively, cells of immature T cell line, R1.1 exert strong DPPIV enzyme activity, which could be down-regulated in the presence of dynorphin-A(1-17) by mechanism that presumably includes non-substrate inhibition. By down-regulating DPPIV, dynorphin-A(1-17) may indirectly affect activity and/or specificity of natural substrates of DPPIV, such as substance P, RANTES, and endomorphins.
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PMID:Dipeptidyl peptidase IV (DPPIV) enzyme activity on immature T-cell line R1.1 is down-regulated by dynorphin-A(1-17) as a non-substrate inhibitor. 1273 31

The cell surface aminopeptidase N (APN/CD13), overexpressed in tumor cells, plays a critical role in angiogenesis. However, potent, selective, and, particularly, noncytotoxic inhibitors ot this protein are lacking, and the present work was undertaken with the aim of developing a new generation of noncytotoxic inhibitors that bind to APN/CD13. In this context, we have synthesized a series of novel flavone-8-acetic acid derivatives. Among the herein described and evaluated compounds, the 2',3-dinitroflavone-8-acetic acid (19b) proved to be the most efficient and exhibited an IC(50) of 25 microM which is 2.5 times higher than that of bestatin (1), the natural known inhibitor of APN/CD13. However, in contrast to bestatin (1), the dinitroflavone 19b did not induce any cytotoxicity to cultured human model cells. The presence of other substituents such as NO(2) or OCH(3) groups at the 3'- or 4'-position of the B phenyl group, or the existence of steric constraints (compounds 24 and 29), did not improve selectivity and potency. The flavone 19b affinity for APN/CD13 is not recovered with other proteases such as matrix metalloproteinase-9 (MMP-9), angiotensin converting enzyme (ACE/CD143), neutral endopeptidase (NEP/CD10), gamma-glutamyl transpeptidase (CD224), or the serine proteases dipeptidyl peptidase IV (DPPIV/CD26) or cathepsin G.
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PMID:Synthesis and biological evaluation of novel flavone-8-acetic acid derivatives as reversible inhibitors of aminopeptidase N/CD13. 1293 Jan 51

Cartilage tissue engineering relies on in vitro expansion of primary chondrocytes. Monolayer is the chosen culture model for chondrocyte expansion because in this system the proliferative capacity of chondrocytes is substantially higher compared to non-adherent systems. However, human articular chondrocytes (HACs) cultured as monolayers undergo changes in phenotype and gene expression known as "dedifferentiation." To gain a better understanding of the cellular mechanisms involved in the dedifferentiation process, our research focused on the characterization of the surface molecule phenotype of HACs in monolayer culture. Adult HACs were isolated by enzymatic digestion of cartilage samples obtained post-mortem. HACs cultured in monolayer for different time periods were analyzed by flow cytometry for the expression of cell surface markers with a panel of 52 antibodies. Our results show that HACs express surface molecules belonging to different categories: integrins and other adhesion molecules (CD49a, CD49b, CD49c, CD49e, CD49f, CD51/61, CD54, CD106, CD166, CD58, CD44), tetraspanins (CD9, CD63, CD81, CD82, CD151), receptors (CD105, CD119, CD130, CD140a, CD221, CD95, CD120a, CD71, CD14), ectoenzymes (CD10, CD26), and other surface molecules (CD90, CD99). Moreover, differential expression of certain markers in monolayer culture was identified. Up-regulation of markers on HACs regarded as distinctive for mesenchymal stem cells (CD10, CD90, CD105, CD166) during monolayer culture suggested that dedifferentiation leads to reversion to a primitive phenotype. This study contributes to the definition of HAC phenotype, and provides new potential markers to characterize chondrocyte differentiation stage in the context of tissue engineering applications.
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PMID:Immunophenotypic analysis of human articular chondrocytes: changes in surface markers associated with cell expansion in monolayer culture. 1538 73

Due to their extracellular orientation, the ectopeptidases CD10, CD13, CD26, and CD143 have numerous functions, including the post-secretory processing of the neuropeptides and peptide hormones involved in the regulation of growth and differentiation in the gastrointestinal tract. We investigated the transcription and expression pattern of these four ectopeptidases in gastric carcinomas (GC), the corresponding non-neoplastic epithelium, a selection of lymph node metastases (LNM), and the MKN28, AGS, NCI-N87, KATO III gastric cancer cell lines. The gastric foveolar epithelium did not express CD10, CD13, or CD143, but the intestinal metaplasia demonstrated strong immunoreactivity at the brush border for all four ectopeptidases. CD10, CD13, and CD143 were significantly up-regulated in GCs and the lymph node metastases, confirming that they are important for the tumor cell biology. However, there is a lack of correlation between expression in intestinal metaplasia and tumor, as well as in tumor and LNM. Cell proliferation assays were performed with MKN28 and AGS, in which inhibition of CD10 significantly reduced the growth of both cell lines, and inhibition of CD13 significantly increased the proliferation of the AGS cells, indicating that the ability to degrade gastrointestinal peptides may play an important role in the pathobiology of gastric cancer.
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PMID:The ectopeptidases CD10, CD13, CD26, and CD143 are upregulated in gastric cancer. 1549 9

We describe N-[(2S)-2-(mercaptomethyl)-3-methylbutanoyl]-4-(1H-pyrazol-1-yl)-L-phenylalanine (GW796406), a vasopeptidase inhibitor (VPI) that possessed approximately 3-fold selectivity for neutral endopeptidase 24.11 (NEP) versus angiotensin-converting enzyme (ACE) in in vitro assays using rat and human enzymes. In the same assays, omapatrilat, the most extensively studied VPI, displayed approximately 3-fold selectivity for ACE. The in vivo ACE and NEP inhibition profile and the liability of the compounds to increase plasma extravasation were compared at two (low and high) therapeutically equivalent intravenous doses in the rat. At the low dose, both agents inhibited ACE activity by approximately 85%. Consistent with their in vitro ACE/NEP selectivity, omapatrilat produced 49% inhibition, whereas GW796406 produced >95% inhibition of NEP. Neither compound increased plasma extravasation. When the low dose was administered to rats pretreated with the NEP inhibitor ecadotril to normalize NEP background to <5% of control, only omapatrilat significantly increased plasma extravasation. At the high dose, omapatrilat and GW796406 produced profound, nonselective inhibition of ACE (>90%) and NEP (>95%), and they significantly increased plasma extravasation. The activity of the agents as inhibitors of dipeptidylpeptidase IV (DPP IV) and aminopeptidase P (APP) was also investigated. Neither compound inhibited DPP IV. Interestingly, omapatrilat, but not GW796406, was a relatively potent inhibitor of APP (IC50 = 260 nM). We investigated whether APP inhibition increased the plasma extravasation liability of GW796406. The low dose of GW796406 administered with apstatin, an APP inhibitor, did not increase plasma extravasation. This finding inferred that APP inhibition is not involved in plasma extravasation in the rat and that APP inhibition does not explain the increased plasma extravasation produced by omapatrilat in NEP-inhibited rats.
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PMID:Mechanism of vasopeptidase inhibitor-induced plasma extravasation: comparison of omapatrilat and the novel neutral endopeptidase 24.11/angiotensin-converting enzyme inhibitor GW796406. 1614 80

Summary Prostasomes are prostate-derived organelles in seminal plasma exhibiting pluripotent properties to facilitate the fertilization process. Seminal prostasome concentration, size distribution and expression of the prostasomal surface antigens CD10, CD13, CD26 and CD59 were examined by flow cytometry. The study group consisted of 79 men with involuntary infertility. Very strong correlations existed between the prostasome expressions of the different CD markers. Significant correlations between prostasome concentration and CD molecules were weak or lacking. Further, no or weak relationships were observed between the prostasomal CD markers and sperm morphology, seminal fructose, neutral alpha-glucosidase activity, zinc and tumour necrosis factor alpha concentrations. Flow cytometry is a practical way to study prostasomes in seminal fluid without prior separation. This is a new technique for evaluation of the role of prostasomes and their functions in male reproductive physiology.
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PMID:Flow cytometric technique for determination of prostasomal quantity, size and expression of CD10, CD13, CD26 and CD59 in human seminal plasma. 1653 55

In this study, a time-course comparison of human articular chondrocytes (HAC) and bone marrow-derived mesenchymal stem cells (MSC) immunophenotype was performed in order to determine similarities/differences between both cell types during monolayer culture, and to identify HAC surface markers indicative of dedifferentiation. Our results show that dedifferentiated HAC can be distinguished from MSC by combining CD14, CD90, and CD105 expression, with dedifferentiated HAC being CD14+/CD90bright/CD105dim and MSC being CD14-/CD90dim/CD105bright. Surface markers on MSC showed little variation during the culture, whereas HAC showed upregulation of CD90, CD166, CD49c, CD44, CD10, CD26, CD49e, CD151, CD51/61, and CD81, and downregulation of CD49a, CD54, and CD14. Thus, dedifferentiated HAC appear as a bona fide cell population rather than a small population of MSC amplified during monolayer culture. While most of the HAC surface markers showed major changes at the beginning of the culture period (Passage 1-2), CD26 was upregulated and CD49a downregulated at later stages of the culture (Passage 3-4). To correlate changes in HAC surface markers with changes in extracellular matrix gene expression during monolayer culture, CD14 and CD90 mRNA levels were combined into a new differentiation index and compared with the established differentiation indices based on the ratios of mRNA levels of collagen type II to I (COL2/COL1) and of aggrecan to versican (AGG/VER). A correlation of CD14/CD90 ratio at the mRNA and protein level with the AGG/VER ratio during HAC dedifferentiation in monolayer culture validated CD14/CD90 as a new membrane and mRNA based HAC differentiation index.
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PMID:Immunophenotypic changes of human articular chondrocytes during monolayer culture reflect bona fide dedifferentiation rather than amplification of progenitor cells. 1755 82

We have recently shown that frizzled-9 (FZD9, CD349) is expressed on the cell surface of cultured mesenchymal stromal cells (MSC) derived from the human bone marrow (BM) and chorionic placenta (PL). To study whether FZD9 is also a marker for naive mesenchymal stem cells (MSC), we analyzed the expression pattern of FZD9 on freshly isolated PL cells and determined the clonogenic potential of isolated FZD9(+) cells using the colony-forming units-fibroblastic (CFU-F) assay. About 0.2% of isolated PL cells were positive for FZD9. Two-color analysis revealed that FZD9(+) PL cells uniformly express CD9, CD63, and CD90, but are heterogeneous for CD10, CD13, and CD26 expression. In contrast to BM-derived MSC, PL-derived MSC expressed only low levels of CD271. Colony assays of sorted cells showed that clonogenic CFU-F reside exclusively in the FZD9(+) but not in the FZD9(-) fraction. Further analysis revealed that CFU-F were enriched by 60-fold in the FZD9(+)CD10(+)CD26(+) fraction but were absent in the FZD9(+)CD10(-)CD26(-) population. Cultured FZD9(+) cells expressed the embryonic stem cell makers Oct-4 and nanog as well as SSEA-4 and TRA1-2-49/6E. In addition, they could be differentiated into functional adipocytes and osteoblasts. This report describes for the first time that FZD9 is a novel and specific marker for the prospective isolation of MSC from human term PL.
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PMID:Prospective isolation and characterization of mesenchymal stem cells from human placenta using a frizzled-9-specific monoclonal antibody. 1792 62


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