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U Kyas

Publications and source records attributed to U Kyas.

7 recordsLinked to original sources
PubMed1998

[The CD95/CD95L system as target for modulation of allogeneic immune responses].

The effects of COS7 cells which constitutively express the apoptosis-inducing human CD95 ligand (COSh95L cells) on in vitro alloimmune responses were investigated. In the presence of COSh95L cells a clear-cut inhibition of alloantigen-induced proliferation was observed. In these cultures fully activated blastoid T cells were absent suggesting that deletion of activated T cells is one mechanism of COSh95L-mediated inhibition of proliferation. Non-fully activated cells were not eliminated in MLR by COSh95L cells but achieved a hyporesponsive state as shown by their failure to proliferate in response to restimulation with alloantigen or mitogen. These data indicate that the effects of CD95L on T cells are heterogeneous. Further analysis of the actions of CD95L in T cells of different activation states and subsets will be crucial to estimate the therapeutical potential of this molecule as target for immunomodulation after allo- and xenotransplantation.

Animals↗
PubMed1992

Effects of human stem cell factor (c-kit ligand) on proliferation of myeloid leukemia cells: heterogeneity in response and synergy with other hematopoietic growth factors.

A novel hematopoietic growth factor, the stem cell factor (SCF), for primitive hematopoietic progenitor cells has recently been purified and its gene has been cloned. In this study we tested the mitogenic activity of recombinant human SCF on myeloid leukemia cells as well as the expression of its receptor. We have investigated the proliferation of 31 myeloid leukemia cell lines as well as fresh myeloid leukemic blasts from 17 patients in a 72-hour 3H-thymidine uptake assay in the presence of various concentrations of recombinant human (rh) SCF alone or in combination with saturating concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, M-CSF, interleukin-3 (IL-3), or erythropoietin (EPO). Only five of 31 lines, but fresh leukemic blasts from 12 of 17 patients with acute myeloid leukemia (AML), significantly responded to SCF. The responding cell lines were of the acute promyelocytic, chronic myeloid, megakaryoblastic, and erythroleukemia origin, the responding blast preparations of all French-American-British subtypes. Synergistic activities of SCF were found with G-CSF, GM-CSF, EPO, and IL-3. To determine the SCF binding sites on leukemic cells, we used 125I-radiolabeled SCF in Scatchard analysis and cross-linking studies. The leukemic cell lines responding to SCF expressed from 2,300 up to 29,000 binding sites per cell. The SCF receptor expression was downregulated in vitro by the presence of its ligand. Cross-linking studies demonstrated a 150-Kd SCF receptor on the surface of all responding myeloid leukemias. This study suggests that SCF may be an important factor for the growth of myeloid leukemia cells, either as a direct stimulus or as a synergistic factor for other cytokines. Furthermore, using polymerase chain reaction analysis of total RNA from the myeloid leukemia lines, we found expression of SCF-mRNA in 17 of 30 lines, suggesting autocrine mechanisms in the growth of a subgroup of leukemic cells by coexpression of SCF and its receptor.

Cell Division↗
PubMed1992

Expression of receptors for granulocyte colony-stimulating factor on neutrophils from patients with severe congenital neutropenia and cyclic neutropenia.

We studied granulocyte colony-stimulating factor (G-CSF) binding sites on neutrophils from patients with severe congenital neutropenia (SCN; Kostmann-syndrome) and cyclic neutropenia (CN) during treatment with recombinant human (rh) G-CSF. G-CSF receptor expression was measured by scatchard analysis. Neutrophils from six healthy controls expressed between 480 and 1,210 binding sites per cell, whereas neutrophils from five SCN patients expressed increased numbers of G-CSF binding sites ranging between 2,100 and 3,900 per cell. Neutrophils from four patients with CN expressed 350 to 1,600 binding sites per cell. The affinity of rhG-CSF to its receptor was similar in patients and controls. These data suggest that SCN patients and CN patients are not defective in G-CSF receptor expression as judged by the numbers of G-CSF binding sites and binding affinity; however, we cannot exclude defects in parts of the G-CSF receptor that may be involved in the signal transduction pathway.

Adolescent↗
PubMed1992

Phenotypical and biochemical characterization of a variant CD45R expression pattern in human leukocytes.

As a result of a regulatory polymorphism a variant pattern of CD45R expression can be found in 8% of healthy individuals. We have previously reported that all resting T cells of these individuals react with CD45RA monoclonal antibodies (mAb) that are directed to the high-molecular mass isoforms (220 and 205 kDa) of the leukocyte common antigen (CD45). In addition, their T cells remain CD45RA+ after in vitro activation. In this report we studied the regulatory CD45R polymorphism in more detail. Flow cytometry studies revealed that CD45RA antigens are weakly expressed on normal monocytes but are absent from granulocytes. In individuals displaying the variant CD45R pattern both monocytes and granulocytes were CD45RA+. In controls and variant T cells CD45RA mAb precipitated two chains with molecular masses of about 220 and 205 kDa. In activated T cells from controls (CD45RA-) neither p220 nor the p205 chain of CD45RA could be detected. However, activated T cells from variant individuals (CD45RA+) did not express p220 but expressed p205 of CD45RA. These data indicate that there is a failure to down-regulate p205 CD45RA in individuals displaying the variant CD45R expression pattern. Since their T cells lost p220 CD45RA during activation the data also suggest that the two isoforms detected by CD45RA mAb can be regulated independently.

Antigens, CD↗
PubMed1986

Phospholipase A2 activity in T-lymphocytes.

Phospholipase A2 activity was shown indirectly in T-lymphocytes from rat thymus and a permanent T-cell line by the liberation of arachidonic acid from phospholipids. In addition, phospholipase A2 activity was measured directly with two different substrates, phosphatidylcholine and labelled E. coli.

Animals↗
PubMed1986

The receptor for interleukin 1 in plasma membranes of the human leukemia cell K 562: biological and biochemical characterization.

Murine interleukin 1 (IL 1) inhibited concentration dependently the proliferation of murine T cell lymphomas and the human leukemic cell line K 562. The cytostatic action of IL 1 was not associated with cytotoxicity and appeared to be irreversible. Changes in the expression of surface antigens, like a rapid decrease of transferrin receptors or, more delayed, an increase in HLA-A, B, C antigen density suggested that a differentiation step was induced by IL 1. This effect of IL 1 was a direct one and most likely mediated by a specific receptor molecule. In order to characterize the receptor for IL 1, highly purified plasma membranes from K 562 were incubated with murine IL 1, and the phosphorylation pattern of plasma membrane proteins was investigated by the addition of radiolabeled ATP. At 0 degree C, IL 1 induced the specific phosphorylation of a 41 kDa membrane protein in a time- and concentration-dependent manner. Analysis of the phosphoamino acid composition revealed that IL 1 induced specifically the phosphorylation of tyrosine residues of the 41 kDa protein. Crosslinking experiments proved that the 41 kDa protein had an IL 1 binding site, strongly suggesting that the 41 kDa protein was the receptor for IL 1 itself. Affinity labeling with an ATP-analogue showed that this protein possessed an ATP binding and cleaving site. We conclude from this that the receptor for IL 1 in the plasma membranes of K 562 is a transmembranous protein of 41 kDa, which possesses a tyrosine specific protein kinase activity with an autophosphorylating capacity.

Animals↗