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)

A human pro-B cell line, named JKB-1, was established from the bone marrow of a 16-year-old girl with acute lymphoblastic leukemia (ALL) in relapse. The origin of the JKB-1 cell line was indicated by its chromosomal and immunologic similarity to the patient's fresh leukemic cells. This cell line has been growing for more than 14 months in suspension culture medium and had a doubling time of about 24 hours. JKB-1 expressed terminal deoxynucleotide transferase (TdT) and early antigens (HLA-DR, CD19, CD24) of B cells, with heavy chain gene rearrangement. However, it did not express late antigens (CD10, CD20, CD21, CD22, CD23) of B cells, light chain gene rearrangement, and cytoplasmic mu-chain. These results suggested that JKB-1 is at the stage of "pro-B" cell or early B-cell precursors. This cell line was induced to differentiate after 7 days of co-incubation with irradiated bone marrow stromal cells because of the expression of pre-B cell antigens (CD10, CD20), cytoplasmic mu-chain, light chain gene rearrangement, and disappearance of TdT, JKB-1 cells adhered to a preestablished bone marrow stromal cell layer with string-like processes under scanning electron microscope. When JKB-1 cells were separated from the stromal layer by a cyclopore membrane with 0.45 micron pore size, they did not differentiate. Bone marrow stromal cell conditioned medium could not induce differentiation either. Thus it was suspected that direct contact between JKB-1 cells and stromal cells was required for differentiation. In methylcellulose semisolid medium, the colony size and number of JKB-1 cells were increased by stem cell factor (SCF), or interleukin (IL)-3, or IL-7, but they were decreased by IL-6. Moreover, SCF synergized with IL-3 or IL-7 to stimulate the proliferation of JKB-1 cells. Because there are very few reproducible models for examining early stages of human B-cell differentiation, the JKB-1 cell line would be useful for studying the relationship between human B-cell differentiation and bone marrow microenvironment, as well as leukemogenesis.
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PMID:Establishment of a human pro-B cell line (JKB-1) and its differentiation of preestablished bone marrow stromal cell layer. 817 77

Neutral endopeptidase 24.11 (NEP/CALLA/CD10), an enzyme expressed on early lymphoid progenitors, neutrophils, and various other cell types, inactivates many biologically active peptides, including the bacterial chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP). Inhibition of CD10/NEP on the surface of human neutrophils (PMNs) in vitro inhibits migration toward this chemotaxin, suggesting that enzymatic inactivation by NEP regulates the neutrophil response to fMLP. Because PMNs in inflammatory sites are exposed to various cytokines, we evaluated the effects of selected cytokines on CD10/NEP activity in vitro. Of five cytokines tested--interleukin-1 (IL-1), IL-6, and IL-8, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor (GM-CSF)--GM-CSF provided the most consistent increase in surface NEP activity. Low concentrations (10(-9)-10(-7) M) of GM-CSF increased NEP activity in a time- and concentration-dependent manner to more than 225% that of control (phosphate-buffered saline-treated) cells. Cytofluorometry of cells stained with a fluorescent antibody to CD10 indicated that GM-CSF increased expression of surface CD10/NEP antigen in a similar manner. The effect of GM-CSF on NEP activity was enhanced still further by simultaneous exposure to IL-1, suggesting that combinations of cytokines may direct and regulate the neutrophil response within an inflammatory site. Rapid upregulation of CD10/NEP underscores the importance of this enzyme for control of peptide mediators of inflammation.
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PMID:Up-regulation of neutral endopeptidase (CALLA) in human neutrophils by granulocyte-macrophage colony-stimulating factor. 831 51

We employed a highly sensitive method to assay protein tyrosine kinase activity in extracts of subpopulations of CD34+ bone marrow progenitor cells isolated by fluorescence activated cell sorting in an attempt to better define how growth-factor induction of enzymatic activity relates to progenitor cell maturation. FACS analysis confirmed that, under the conditions employed, essentially all of the CD34+ cells in adult human marrow that lacked the CD38 antigen were devoid of the myeloid maturation marker CD33 as well as the lineage antigens: CD10, 13, 14, 15, 16, 19, 71 and glycophorin A. A variable portion (50-90%) of these CD34+, CD38- progenitor cells expressed HLA-DR. CD34+, CD38- cells that did not express HLA-DR were found to lack detectable levels of either membrane or cytosolic tyrosine kinase activity. HLA-DR+ progenitor cells that lacked CD38 possessed elevated levels of cytosolic tyrosine kinase activity but only low levels of plasma membrane activity. In contrast, CD34+ cells that expressed CD38 (and HLA-DR) possessed high levels of membrane-associated tyrosine kinase activity. A cocktail of haemopoietic growth factors that included IL-3, IL-6 and stem cell factor effectively induced tyrosine kinase activity in CD34+, CD38-, HLA-DR- progenitor cells. Growth factor induction of tyrosine kinase activity in these cells was not inhibited by actinomycin D or cyclohexamide. Most of the tyrosine kinase activity induced by these growth factors was recovered from the cytosolic fraction of disrupted cells. Thus, induction of cytosolic tyrosine kinase activity is an early event in the response of uncommitted haemopoietic cells to haemopoietic growth factors. Subsequent activation of membrane tyrosine kinases may initiate key transduction processes as these cells begin to differentiate.
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PMID:Growth factor induction of cytosolic protein tyrosine kinase activity in human haemopoietic progenitor cells isolated by flow cytometry. 865 68

The severe combined immunodeficient (SCID) mouse model is an important tool with which to study new strategies for treating hematologic neoplasia. For these experiments, a large number of human cell lines growing in SCID mice are a prerequisite. We describe a new Epstein-Barr virus (EBV)-positive B cell line, designated BEVA, with a complex karyotype including translocations t(14:18)(q32;q21) and t(4;11) (q21;q23) that meets this need. As demonstrated by Southern blot analysis, BCL2 at 18q21, but not MLL/ALL1 at 11q23, was involved in these translocations. BEVA cells coexpressed lymphoid (IgG-kappa, CD19, CD20, CD21, and CD24) and myeloid (CD11b, CD15, and CDw65) markers. Interestingly, the cell line was established from the bone marrow culture of a patient with acute myeloid leukemia (AML). Examination of bone marrow biopsy specimens suggested the presence of non-Hodgkin's lymphoma (NHL) in this patient in addition to AML. In vitro and in vivo growth characteristics of the BEVA cell line were compared with the previously described EBV-positive B cell line DoHH2, also carrying a translocation t(14;18)(q32;q21). These DoHH2 cells additionally expressed CD10, whereas, in contrast to BEVA cells, only a small population of DoHH2 cells showed expression of CD44. Both cell lines showed similar growth characteristics in vitro, but reacted differently to cytokines, including interleukin (IL)-4, IL-6, IL-7, and alpha-interferon (IFN). Upon inoculation in SCID mice, marked differences were observed in the dissemination patterns of the BEVA or DoHH2 cells. Although both cell lines circulated in the blood and were predominantly found in murine bone marrow and lymphoid tissues, DoHH2 cells infiltrated the murine spleens, whereas BEVA cells could only rarely be detected in these tissues. In contrast to DoHH2 cells, BEVA cells gave rise to tumor masses in liver, kidney, and para-aortal or mesenteric lymph nodes. The relationship between these in vitro differences and the observed differences in dissemination of both cell lines is discussed.
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PMID:Characterization of a novel malignant B cell line with t(14;18) and t(4;11) established from a patient with acute monoblastic leukemia. 929 3

The effects of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3 and IL-6 on clonogenic growth of blast-cell progenitors from 19 immunologically defined CD10-positive B-lineage acute lymphoblastic leukemias (ALL) coexpressing (My+ALLs) or not (My-ALLs) myeloid antigens have been studied. Our results demonstrate that GM-CSF was able to support the clonogenic growth of blast cells from My+ALLs, being totally ineffective on My-All samples. Accordingly, both alpha and beta chains of GM-CSF receptor (R) were expressed by My+ALL blasts, as investigated by reverse-transcriptase polymerase chain reaction (RT-PCR). Colony cells from GM-CSF-stimulated My+ALL cultures displayed the same immunophenotype as primary leukemic cells at diagnosis (CD10+, CD19+, CD22+), and retained the expression of myeloid-associated antigens and of GM-CSF-R transcripts. Moreover, My+ALL blasts showed a preferential sensitivity to the growth-promoting activity of IL-3 and IL-6, as compared with My-ALL cells. In addition to rearrangements of the JH region of immunoglobulin genes, My+ALL cells showed aberrant rearrangements of gamma (three cases) and beta (two cases) T-cell receptor genes, as well as of bcr sequences (three cases). Our data, showing an unexpected cross-lineage response of My+ALLs to GM-CSF, and their preferential stimulation by IL-3 and IL-6, as compared with My-ALLs, further support the concept that My+ALLs represent a separate entity with unique biological features.
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PMID:Human granulocyte-macrophage colony-stimulating factor supports the clonogenic growth of B-lineage acute lymphoblastic leukemias expressing myeloid antigens. 942 72

Epstein-Barr-virus-associated posttransplant lymphoproliferative disease ranges from transient lymphadenitis to aggressive lymphoma. This study characterizes an in vitro model to study the pathogenesis of this disease with a cell culture system. Five B-cell lines derived from posttransplant lymphoproliferative disease tissue were characterized with regard to immunophenotype, karyotype, molecular genetics, cytokine production, and growth regulation. All cell lines expressed CD19, CD21, CD22, CD43, and CD77, but not CD10 antigens. Immunoglobulin light chain restriction was seen in four of five cell lines, and cytogenetic abnormalities were demonstrable in three of the five. Cells proliferating in culture contained multiple Epstein-Barr virus episomes and showed lytic viral replication. All cell lines produced tumor necrosis factor-beta and interleukin-10 without evidence of autocrine growth regulatory loops involving these cytokines. No evidence of IL-1 alpha, IL-2, IL-4, IL-5 or IL-6 production was found by reverse transcriptase polymerase chain reaction. Adding 500 U IFN-alpha/ml to the culture medium resulted in 30% inhibition of [3H]thymidine incorporation.
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PMID:In vitro culture of B-lymphocytes derived from Epstein-Barr-virus-associated posttransplant lymphoproliferative disease: cytokine production and effect of interferon-alpha. 946 86

A novel biphenotypic leukemia cell line, NALM-29, was established from a 46-year-old Japanese male patient with acute lymphoblastic leukemia (ALL). The primary leukemic blasts showed a common ALL phenotype with CD19+, CD10+, CD13-, HLA-DR+ and Igs-. NALM-29 cells display biphenotypic characteristics: expression of the intracellular enzyme myeloperoxidase at the mRNA and protein level and cell surface positivity for CD19, CD10, CD13, CD33 and HLA-DR. NALM-29 fulfills EGIL criteria as B-cell precursor (BCP) leukemia B-II type. NALM-29 cells have a lymphoblastic morphological appearance; the immunoglobulin heavy chain gene is rearranged. NALM-29 cells responded significantly to the proliferative stimuli of FLT-3 ligand and IL-7, but not to GM-CSF, IL-3, IL-6, PIXY-321 or SCF. Proliferation of cells was inhibited significantly by IL-4, TNF-alpha or TNF-beta treatment. Cytogenetic analysis revealed the characteristic t(9;22)(q34;q11); expression of the m-bcr e1-a2 BCR-ABL fusion gene (typically found in ALL) was determined by PCR amplification of cDNA. The immunological, cytogenetic and functional characterization of NALM-29 suggests that this cell line may represent a scientifically significant in vitro model for BCP-type leukemia cells with biphenotypic characteristics.
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PMID:A novel biphenotypic B-cell precursor leukemia cell line (NALM-29) carrying t(9;22)(q34;q11) established from a patient with acute leukemia. 1045 71

The role of neuropeptides in initiating and modulating airway inflammation was examined in a human bronchial epithelial cell line (i.e. BEAS-2B). At a range of concentrations, exposure of BEAS-2B cells to Substance P (SP) or calcitonin gene related protein resulted in immediate increases in intracellular calcium ([Ca(2+)](i)), the synthesis of the transcripts for the inflammatory cytokines, IL-6, IL-8 and TNFalpha after 2 h exposure, and the release of their proteins after 6 h exposure. Addition of thiorphan (100 nM), an inhibitor of neutral endopeptidase, enhanced the levels of SP-stimulated cytokine release. Stimulation of IL-6 by SP occurred in a conventional receptor-mediated manner as demonstrated by its differential release by fragments SP 4-11 and SP 1-4 and by the blockage of IL-6 release with the non-peptide, NK-1 receptor antagonist, CP-99 994. In addition to the direct stimulation of inflammatory cytokines, SP (0.5 microM), in combination with TNFalpha (25 units/ml), synergistically stimulated IL-6 release. BEAS-2B cells also responded to the botanical irritant, capsaicin (10 microM) with increases in [Ca(2+)](i) and IL-8 cytokine release after 4 h exposure. The IL-8 release was dependent on the presence of extracellular calcium. Capsaicin-stimulated increases of [Ca(2+)](i) and cytokine release could be reduced to control levels by pre-exposure to capsazepine, an antagonist of capsaicin (i.e. vanilloid) receptor(s) or by deletion of extracellular calcium from the exposure media. The present data indicate that the BEAS-2B human epithelial cell line expresses neuropeptide and capsaicin-sensitive pathways, whose activation results in immediate increases of [Ca(2+)](i) stimulation of inflammatory cytokine transcripts and the release of their cytokine proteins.
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PMID:Neuropeptides and capsaicin stimulate the release of inflammatory cytokines in a human bronchial epithelial cell line. 1065 23

Seven patients with peripheral B-cell lymphoma associated with hemophagocytic syndrome are reported. In all cases, the histologic subtype was diffuse large B-cell lymphoma. Hemophagocytic features were noted in the bone marrow with lymphomatous infiltration. Hemophagocytic syndrome occurred with presentation of the lymphoma and was characterized by high fever, cytopenias, and elevated levels of lactate dehydrogenase, ferritin, C-reactive protein, and cytokines [interferon gamma, macrophage colony-stimulating factor, soluble interleukin (sIL)-2R, and IL-6] without evidence of infection. The phenotypes of lymphomas were suspected CD19+, CD20+, S-Ig+, CD10-, and coexpression of CD5 in some cases. Flow cytometric analysis showed a low CD4/CD8 ratio in peripheral blood and bone marrow. We suggest that the pathogenesis of hemophagocytic syndrome is hypercytokinemia induced by a proliferation of reactive CD8+ T cells. Previous reports of B-cell lymphoma with hemophagocytic syndrome demonstrated similar clinical manifestations and poor prognoses. The invasion patterns of these diffuse large B-cell lymphomas with hemophagocytosis may be classified into three groups: microscopic lymph-node involvement type, gross lymph-node involvement type, and splenic lymphoma type. Although hemophagocytic syndromes have been reported to be associated with T-cell lymphomas, our results indicate an association with diffuse large B-cell lymphoma.
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PMID:B-cell lymphoma-associated hemophagocytic syndrome: clinicopathological characteristics. 1096 86

We investigated the levels of 6 different cytokines in the sera of 10 newly diagnosed patients with B cell lineage acute lymphoblastic leukemia (ALL) and detected a significant increase in IL-6 and IFN-alpha serum levels in comparison to that of healthy controls. Whole blood cell cultures of 10 ALL patients and 20 control individuals were induced with classical cytokine inducers, such as virus, PHA and LPS, and their ability to produce 9 different cytokines was compared. Blood cells of ALL patients produced significantly less IL-1alpha, IL-1beta, IL-10 and TNF-alpha than control cells and not significanly lower levels of IL-6, but comparable with control levels of IL-2, IL-4. rHuGM-CSF added to cell cultures 24 h before induction significantly enhanced the production of IL-1alpha, IL-1beta and TNF-alpha in controls, but only IL-1alpha and IL-1beta in the blood cell cultures of patients with ALL. GM-CSF did not significantly influence the production of IFN-alpha, IFN-gamma, IL-2, IL-4 and IL-10 in the control cells and the cells of ALL patients. The patients examined differed not only in the expression of CD10 and CD34 antigens on blast cells, but also in the reaction to GM-CSF treatment, which was found as very high standard deviation values. We suppose that these differences can partially explain the different effects of GM-CSF when used to ameliorate neutropenia of ALL patients after chemotherapy and to reduce the incidence of microbial infections.
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PMID:Cytokine production in whole blood cell cultures of patients with B-lineage acute lymphoblastic leukemia. The influence of granulocyte-macrophage colony-stimulating factor. 1126 94


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