Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nature of effectors of interferon (IFN)-alpha or IFN-gamma-induced killer cell activity remains unclear. The aim of this study was to examine killer cell activity induced by IFN-alpha alone, IFN-gamma alone or a combination of both in patients with renal cell carcinoma (RCC) and to determine the phenotypic patterns of these effectors. The study group included 14 patients (12 men and 2 women, median age 64 years, range 36-77) with confirmed RCC. Peripheral blood mononuclear cells (PBMC) from RCC patients or normal volunteers were cultured with IFN-alpha alone, IFN-gamma alone or a combination of both. Cytotoxic activity was assayed against ACHN cells. Subpopulations of effector cells in IFN-induced killer cell activity were characterized by cell sorting. The most effective type of IFN and the optimal concentration of IFN necessary to induce the maximal killer cell activity varied among RCC patients. The killer activity induced by a combination of IFN-alpha and IFN-gamma was significantly greater than that induced by IFN-alpha or IFN-gamma alone. The greatly increased killer activity induced by IFN-alpha and IFN-gamma was seen in the subpopulations CD3(-) CD16(+), CD3(-) CD56(+) and subpopulation CD3(+)CD4(-), CD3(-)CD16(+), CD3(-)CD56(+), CD57(+)CD16(-), respectively. An optimal type of IFN and optimal concentration of IFN seem to increase the effective rate of treatment of RCC. In addition, the role of IFN-alpha seems to be different from that of IFN-gamma in host defense against RCC. A combination treatment with IFN-alpha and IFN-gamma seems to be suitable to increase the effective rate if we could reduce the side effects of IFNs.
Int J Mol Med 2002 Sep
PMID:The effectors of killer activity induced by interferon-alpha and gamma in peripheral blood mononuclear cells. 1216 7

Dendritic cells (DCs) in the rheumatoid arthritis (RA) joint mediate the immunopathological process and act as a potent antigen presenting cell. We compared the expression of co-stimulatory and adhesion molecules on DCs in RA patients versus controls with traumatic joint lesions and evaluated the correlation between the immunophenotypical presentation of DCs and the clinical status of the disease. Samples of peripheral venous blood, synovial fluid (SF) and synovial tissue (ST) were obtained from 10 patients with RA at the time of hip or knee replacement and from 9 control patients with knee arthroscopy for traumatic lesions. Clinical status was appreciated using the DAS28 score. Blood, SF and dissociated ST cell populations were separated by centrifugation and analyzed by flow cytometry. Cells phenotypes were identified using three-color flow cytometry analysis for the following receptors HLA-DR, CD80, CD83, CD86, CD11c, CD18, CD54, CD58, CD3, CD4, CD8, CD19, CD20, CD14, CD16, CD56. HLA-DR molecules, co-stimulatory receptors CD80, CD86, CD83 and adhesion molecules CD18, CD11c, CD54, CD58, were analyzed by two-color immunofluorescence microscopy on ST serial sections. In patients with active RA (DAS28>5.1) we found a highly differentiated subpopulation of DCs in the ST and SF that expressed an activated phenotype (HLA-DR, CD86+, CD80+, CD83+, CD11c+, CD54+, CD58+). No differences were found between circulating DCs from RA patients and control patients. Our data suggest an interrelationship between clinical outcome and the immunophenotypical presentation of DCs. Clinical active RA (DAS28>5.1) is associated with high incidence of activated DCs population in the ST and SF as demonstrated by expression of adhesion and co-stimulatory molecules.
J Cell Mol Med
PMID:Co-stimulatory and adhesion molecules of dendritic cells in rheumatoid arthritis. 1241 58

A novel membrane protein has been identified in the course of screening for differentially expressed cDNAs in human embryonic hematopoietic sites. This 37- to 38-kDa molecule, designated KLIP-1 (killer lineage protein), consisting of 350 amino acids and containing five transmembrane domains, is encoded by the 5093-bp KLIP-1 gene, composed of nine exons and located on chromosome 6 (6p21.1-6p21.2). We found the KLIP-1 protein to be expressed by nucleated hematopoietic cells, from early embryonic hematopoietic stem cells through mature adult blood lymphoid lineages, either as membrane or as cytoplasmic molecules. In day-30/32 human embryo sections, KLIP-1 protein expression is restricted to circulating hematopoietic cells at hematopoiesis sites. Membrane KLIP-1 is expressed by fetal and adult GP-A(+) erythroblasts, the fetal liver CD34(+) subset, fetal spleen, and adult bone marrow CD56(+) NK and CD19(+) B cells. Among mature blood cells, surface KLIP-1 expression is restricted to CD56(+) NK cells, indicating KLIP-1 to be a novel marker of this population. Altogether, these results indicate that membrane export of KLIP-1 antigen is developmentally and ontogenetically regulated. The high degree of conservation of the KLIP-1 protein sequence among mammals strongly suggests that it plays an important role during hematopoiesis and may exercise similar functions in human and mouse blood cells. The KLIP-1 molecule may therefore constitute a powerful tool for improving knowledge of both human hematopoiesis and NK cell ontogeny and immune functions.
Blood Cells Mol Dis
PMID:Characterization of a novel hematopoietic marker expressed from early embryonic hematopoietic stem cells to adult mature lineages. 1249 Feb 90

Although a number of studies on the phenotypic changes that occur after T-cell activation have already been published, the specific immunophenotypic features of T-lymphocytes and the frequency at which TCR-variable region (TCR-V) restricted T-cell expansions occur "in vivo" during acute viral infection still remains to be established. We report on the immunophenotype and TCR-V repertoire of peripheral blood T-cells from 28 patients with acute infectious mononucleosis. Immunophenotypic studies were performed by flow cytometry using direct immunofluorescence techniques and stain-and-then-lyse sample preparation protocols with three- and four-colour combinations of monoclonal antibodies directed against a large panel of T- and NK-cell associated markers, activation- and adhesion-related molecules and TCR-Vbeta, -Vgamma and -Vdelta families. Nearly all patients (27/28) showed a massive expansion of CD8(+)/TCRalphabeta(+) T cells, the majority (>90%) of which displayed an immunophenotype compatible with T-cell activation: CD2(+high), CD7(+low), CD11a(+high), CD38(+high), HLA-DR(+high), CD28(+/-low), CD45RO(+high), CD45RA(-/+low), CD11b(-/+low), CD11c(+/-low), CD16(-), CD56(-), CD57(-), CD62L(-), CD94(-), CD158a(-), CD161(-), NKB1(-). Additionally, the levels of both CD3 and CD5 were slightly decreased compared to those found in normal individuals. Late-activation antigens, such as CD57, were found in small proportions of CD8(+)/TCRalphabeta(+) T-cells. Increased numbers of CD4(+)/TCRalphabeta(+) T-cells, TCRgammadelta(+) T-cells and NK-cells were also noticed in 17, 16 and 13 of the 28 cases studied, respectively. Evidence for activation of CD4(+)/TCRalphabeta(+) and TCRgammadelta(+) T-cells relied on changes similar to those described for CD8(+)/TCRalphabeta(+) although less pronounced, except for higher levels of both CD5 and CD28 in the absence of reactivity for CD11c on CD4(+)/TCRalphabeta(+) T-cells and higher levels of CD161 and CD94 on TCRgammadelta(+) T-cells. Small expansions of one or more TCR-Vbeta families accounting for 12 +/- 7% of either the CD8(+)/TCRalphabeta(+) or the CD4(+)/TCRalphabeta(+) T-cell compartment were found in 12 of 14 patients studied, whereas the distribution of the TCR-Vgamma and -Vdelta repertoires tested in 2 of the individuals with expanded TCRgammadelta(+) T-cells was similar to that observed in control individuals. The results presented here provide evidence for an extensive T-cell activation during acute viral infection and establish the immunophenotype patterns associated with this condition.
Blood Cells Mol Dis
PMID:Immunophenotype and TCR-Vbeta repertoire of peripheral blood T-cells in acute infectious mononucleosis. 1266 82

In the present work, we studied the effects of several growth factors on survival and proliferation of freshly isolated neural progenitors expressing the polysialylated form of neural cell adhesion molecule (PSA-NCAM). Cells were obtained from postnatal day 2 rat forebrain, using isolation method. We found that (1) insulin-like growth factor 1 (IGF-1) exerts a powerful survival effect by inhibiting apoptotic cell death, (2) epidermal growth factor (EGF) strongly increases cell proliferation, (3) the combination of IGF-1 plus EGF promotes cellular expansion, (4) basic fibroblast growth factor displays only a weak mitogenic effect, and (5) platelet-derived growth factor-AA (PDGF-AA) has no effect on cell survival and proliferation. These results suggest that the postnatal PSA-NCAM(+) progenitors characterized in the present work may represent a transitional stage, between the embryonic EGF-responsive neural progenitors and the postnatal PSA-NCAM(+) progenitors already described that are PDGF-responsive. For these "early PSA-NCAM(+) progenitors," insulin-like growth factor 1 and EGF seem to play a pivotal role in the control of cell death and cell proliferation.
Mol Cell Neurosci 2003 Feb
PMID:Control of cell survival and proliferation of postnatal PSA-NCAM(+) progenitors. 1267 27

In the present study, we analyzed the immunological characteristics of mononuclear cells (MNC) isolated from both neonatal umbilical cord blood (UCB) and maternal peripheral blood (MPB) during the delivery. The in vitro proliferative response of UCB T lymphocytes was significantly reduced compared to the maternal response to phytohemagglutinin A, pokeweed mitogen, and alloantigen stimulation, in correlation with the lower percentage of UCB than MPB lymphocytes, but not with that of B cells. The mean cytotoxic activity level of interleukin-2 (IL-2)-activated natural killer (NK) was higher in UCB than in MBP, whereas the percentage of CD56(+) NK cell count was similar. Our results show differences in the immune reactivity of T and B lymphocytes from neonate and adult isolated under similar physiological conditions.
Exp Mol Pathol 2003 Aug
PMID:Phenotype and function of lymphocytes from the neonatal umbilical cord compared to paired maternal peripheral blood cells isolated during delivery. 1283 24

The aim of the present study was to characterise natural cell-mediated cytotoxicity against COS-7 cells transfected with potentially oncogenic HPV-8 L1 DNA sequences cloned in sense and antisense orientation and to evaluate their lysis by peripheral blood lymphocytes (PBL) from patients with epidermodysplasia verruciformis (EV), a rare disease associated with life-long infection by specific HPV types. COS-7 cells were transfected with HPV-8 Hinc II restriction fragment (nucleotide positions 5434-7654) cloned in sense (COS-L1S) and antisense (COS-L1A) orientation into pCB6 expression vector. Cytotoxic activity of isolated PBL against COS cell lines as well as K562 erythroleukaemic cells was evaluated by 51Cr-release assay. We found that lymphocytes responsible for natural lysis of COS and K562 cells are CD3-negative CD56-positive natural killer (NK) cells. Analysis of NK cell cytotoxic activity against different COS cell lines has revealed that lymphocytes from healthy subjects killed COS-L1S cells significantly more efficiently than wild COS-7 and COS-L1A cells. Significantly more efficient lysis of COS-L1S cells was also observed in EV patients. Thus, expression of HPV L1 renders target cells more susceptible to NK-mediated cytotoxicity that may enable more effective elimination of transformed cells.
Int J Mol Med 2004 Jan
PMID:Natural cell-mediated cytotoxicity of peripheral blood lymphocytes against target cells transfected with epidermodysplasia verruciformis-specific human papillomavirus type 8 L1 DNA sequences. 1465 93

The progeny of neural stem cells in the subventricular zone (SVZ) of the adult mammalian brain consists in polysialylated NCAM-expressing immature neurons (PSA(+) cells), which migrate to the olfactory bulb (OB) to differentiate into GABAergic interneurons. We purified murine PSA(+) cells directly from the adult brain by FACS and analyzed their gene expression profile by SAGE. Comparative analyses led to the identification of precursor-enriched genes, including Survivin, Sox-4, Meis2, Dishevelled-2, C3aR1 and Riken 3110003A17, and many so far uncharacterized transcripts. Cluster analysis showed that groups of genes involved in axon guidance and gene clusters implicated in chemotaxis are strongly upregulated, indicating a role of both cues in the control of cell migration in the adult brain. Furthermore, genes involved in apoptosis and cell proliferation are co-expressed, suggesting that the amount of precursors that is present in the adult brain is a result of an equilibrium of these processes.
Mol Cell Neurosci 2004 Apr
PMID:Purification of neuronal precursors from the adult mouse brain: comprehensive gene expression analysis provides new insights into the control of cell migration, differentiation, and homeostasis. 1508 Aug 97

The effects of hormone stimulation for IVF treatment on endometrial receptivity remain controversial. Since CD56(bright) natural killer (NK) cells in the endometrium positively contribute to implantation and decidualization whereas CD56(dim) NK cells are negatively associated with reproduction, shifts in the balance between those cells will affect receptivity. Therefore, we compared the leukocyte composition in the endometrium of IVF women (n=20) with non-pregnant women (n=18) in a natural cycle, as a parameter for endometrial quality. Biopsies were obtained 7 days after ovulation. Histological dating of the endometrium showed no increased endometrial advancement after IVF treatment as compared to the control group. Flow cytometric analysis of leukocyte subsets showed that hormonal stimulation positively affected the CD56(bright)/CD56(dim) ratio in the endometrium by a relative decrease in the cytotoxic CD56(dim)CD16(+) NK cell numbers. The relative number of T-cells remained unaffected, while the number of non-T and non-NK cells (i.e. B-cells and macrophages) was higher in the IVF group. These effects were restricted to the endometrium and not observed in peripheral blood. Within the CD56(bright) population we could identify a distinct subset of NK cells (CD56(superbright)) that was unique for the endometrium. We conclude that hormonal stimulation for IVF treatment positively affects the CD56(bright)/CD56(dim) ratio of the endometrium during the window of implantation and does not affect endometrial advancement.
Mol Hum Reprod 2004 Jul
PMID:Hormonal stimulation for IVF treatment positively affects the CD56bright/CD56dim NK cell ratio of the endometrium during the window of implantation. 1515 17

Proliferation of activated T cells and CD56 bright natural killer (Cytokine Growth Factor Rev 13:169-183, 1995) cells caused by interleukin-2 (IL-2) has been exploited in IL-2-based therapies for the treatment of metastatic renal cell carcinoma and melanoma (J Clin Oncol 13:688-696, 1995; J Clin Oncol 17: 2105-2116, 1999). In this study, we demonstrate the potentially improved therapeutic value of IL-2 variants engineered to gain 15- to 30-fold increased affinity for the IL-2 receptor alpha-subunit (IL-2Ralpha). A novel pulsed bioassay was used to more closely approximate the rapid systemic clearance pharmacokinetics of cytokines such as IL-2, compared with conventional static bioassays. In this assay, mutants with increased affinity for IL-2Ralpha exhibit significantly increased activity for T-cell proliferation, whereas static bioassays not only fail to reveal the increased activity resulting from enhanced IL-2Ralpha affinity (false negatives), but also suggest improved activity for another mutant without enhanced activity in the pulsed assay (false positive). Our studies on the mechanism leading to increased activity of IL-2 mutants with increased IL-2Ralpha affinity suggest that cell-surface IL-2Ralpha acts as a ligand reservoir for the IL-2 mutants. This leads to increased cell-surface persistence of the IL-2 mutants with increased IL-2Ralpha affinity in cell-surface ligand reservoirs and consequently increased integrated growth signal. Furthermore, a mathematical model predicts increased persistence of cell surface-bound IL-2 in vivo for enhanced IL-2Ralpha-binding IL-2 mutants, suggesting potentially improved therapeutic value of allowing cellular capture of ligands in persistent cell-surface reservoirs. Finally, our findings emphasize the critical choice of appropriate bioassays to evaluate engineered proteins and other drugs.
Mol Pharmacol 2004 Oct
PMID:Interleukin 2 (IL-2) variants engineered for increased IL-2 receptor alpha-subunit affinity exhibit increased potency arising from a cell surface ligand reservoir effect. 1538 40


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