scholarly journals Inhibition of human lymphocyte proliferation by monoclonal antibody to transferrin receptor

Blood ◽  
1983 ◽  
Vol 62 (4) ◽  
pp. 821-826 ◽  
Author(s):  
J Mendelsohn ◽  
I Trowbridge ◽  
J Castagnola
Keyword(s):  
Cell Cycle ◽  
Monoclonal Antibody ◽  
Lymphocyte Proliferation ◽  
Human Lymphocytes ◽  
Nitrilotriacetic Acid ◽  
S Phase ◽  
Inhibitory Effects ◽  
Mitogenic Response ◽  
Cell Cycle Inhibition ◽  
Partial Reversal

Abstract A monoclonal antibody, 42/6, which blocks the binding of transferrin to its receptor on the cell membrane, inhibits proliferation of human lymphocytes stimulated by phytohemagglutinin. Anti-receptor antibody B3/25, which does not block transferrin binding, does not alter the mitogenic response. Addition of soluble iron, in the form of ferric nitrilotriacetic acid, results in partial reversal of inhibition. Lymphocytes in the quiescent phase of the cell cycle at the time of 42/6 antibody addition are unable to traverse S phase, whereas cells actively proliferating when antibody is added are sensitive to its inhibitory effects throughout all phases of the cell cycle. Inhibition is static rather than cidal, since it can be reversed by removal of antibody after up to 48 hr of exposure.

scholarly journals Inhibition of human lymphocyte proliferation by monoclonal antibody to transferrin receptor

Blood ◽  
1983 ◽  
Vol 62 (4) ◽  
pp. 821-826 ◽  
Author(s):  
J Mendelsohn ◽  
I Trowbridge ◽  
J Castagnola
Keyword(s):  
Cell Cycle ◽  
Monoclonal Antibody ◽  
Lymphocyte Proliferation ◽  
Human Lymphocytes ◽  
Nitrilotriacetic Acid ◽  
S Phase ◽  
Inhibitory Effects ◽  
Mitogenic Response ◽  
Cell Cycle Inhibition ◽  
Partial Reversal

A monoclonal antibody, 42/6, which blocks the binding of transferrin to its receptor on the cell membrane, inhibits proliferation of human lymphocytes stimulated by phytohemagglutinin. Anti-receptor antibody B3/25, which does not block transferrin binding, does not alter the mitogenic response. Addition of soluble iron, in the form of ferric nitrilotriacetic acid, results in partial reversal of inhibition. Lymphocytes in the quiescent phase of the cell cycle at the time of 42/6 antibody addition are unable to traverse S phase, whereas cells actively proliferating when antibody is added are sensitive to its inhibitory effects throughout all phases of the cell cycle. Inhibition is static rather than cidal, since it can be reversed by removal of antibody after up to 48 hr of exposure.

scholarly journals TIME SEQUENCE OF NUCLEAR PORE FORMATION IN PHYTOHEMAGGLUTININ-STIMULATED LYMPHOCYTES AND IN HELA CELLS DURING THE CELL CYCLE

1972 ◽  
Vol 55 (2) ◽  
pp. 433-447 ◽  
Author(s):  
Gerd G. Maul ◽  
Helmut M. Maul ◽  
Joseph E. Scogna ◽  
Michael W. Lieberman ◽  
Gary S. Stein ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
Hela Cells ◽  
Pore Formation ◽  
Human Lymphocytes ◽  
Time Sequence ◽  
S Phase ◽  
Nuclear Pore ◽  
Nuclear Surface ◽  
Nuclear Pores

The time sequence of nuclear pore frequency changes was determined for phytohemagglutinin (PHA)-stimulated human lymphocytes and for HeLa S-3 cells during the cell cycle. The number of nuclear pores/nucleus was calculated from the experimentally determined values of nuclear pores/µ2 and the nuclear surface. In the lymphocyte system the number of pores/nucleus approximately doubles during the 48 hr after PHA stimulation. The increase in pore frequency is biphasic and the first increase seems to be related to an increase in the rate of protein synthesis. The second increase in pores/nucleus appears to be correlated with the onset of DNA synthesis. In the HeLa cell system, we could also observe a biphasic change in pore formation. Nuclear pores are formed at the highest rate during the first hour after mitosis. A second increase in the rate of pore formation corresponds in time with an increase in the rate of nuclear acidic protein synthesis shortly before S phase. The total number of nuclear pores in HeLa cells doubles from ∼2000 in G1 to ∼4000 at the end of the cell cycle. The doubling of the nuclear volume and the number of nuclear pores might be correlated to the doubling of DNA content. Another correspondence with the nuclear pore number in S phase is found in the number of simultaneously replicating replication sites. This number may be fortuitous but leads to the rather speculative possibility that the nuclear pore might be the site of initiation and/or replication of DNA as well as the site of nucleocytoplasmic exchange. That is, the nuclear pore complex may have multiple functions.

scholarly journals Ovine herpesvirus-2-encoded microRNAs target virus genes involved in virus latency

2014 ◽  
Vol 95 (2) ◽  
pp. 472-480 ◽  
Author(s):  
Aayesha Riaz ◽  
Inga Dry ◽  
Claire S. Levy ◽  
John Hopkins ◽  
Finn Grey ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Lymphocyte Proliferation ◽  
Luciferase Reporter ◽  
Mrna Levels ◽  
Malignant Catarrhal Fever ◽  
Virus Latency ◽  
Cell Cycle Inhibition ◽  
Host Genes ◽  
Virus Biology

Herpesviruses encode microRNAs (miRNAs) that target both virus and host genes; however, their role in herpesvirus biology is understood poorly. We identified previously eight miRNAs encoded by ovine herpesvirus-2 (OvHV-2), the causative agent of malignant catarrhal fever (MCF), and have now investigated the role of these miRNAs in regulating expression of OvHV-2 genes that play important roles in virus biology. ORF20 (cell cycle inhibition), ORF50 (reactivation) and ORF73 (latency maintenance) each contain predicted targets for several OvHV-2 miRNAs. Co-transfection of miRNA mimics with luciferase reporter constructs containing the predicted targets showed the 5′ UTRs of ORF20 and ORF73 contain functional targets for ovhv-miR-2 and ovhv2-miR-8, respectively, and the 3′ UTR of ORF50 contains a functional target for ovhv2-miR-5. Transfection of BJ1035 cells (an OvHV-2-infected bovine T-cell line) with the relevant miRNA mimic resulted in a significant decrease in ORF50 and a smaller but non-significant decrease in ORF20. However, we were unable to demonstrate a decrease in ORF73. MCF is a disease of dysregulated lymphocyte proliferation; miRNA inhibition of ORF20 expression may play a role in this aberrant lymphocyte proliferation. The proteins encoded by ORF50 and ORF73 play opposing roles in latency. It has been hypothesized that miRNA-induced inhibition of virus genes acts to ensure that fluctuations in virus mRNA levels do not result in reactivation under conditions that are unfavourable for viral replication and our data supported this hypothesis.

scholarly journals Lymphocyte cell-cycle analysis by flow cytometry. Evidence for a specific postmitotic phase before return to G0.

1980 ◽  
Vol 85 (2) ◽  
pp. 459-465 ◽  
Author(s):  
D P Richman
Keyword(s):  
Cell Cycle ◽  
Human Lymphocytes ◽  
Late Phase ◽  
S Phase ◽  
Cycle Phase ◽  
Thymidine Uptake ◽  
Large Numbers ◽  
Distinct Cell ◽  
Lymphocyte Cell ◽  
Supravital Staining

We studied the cell cycle of lectin-stimulated human lymphocytes, making use of a flow cytometer. The RNA and DNA content of large numbers of individual cells was determined by supravital staining with acridine orange. The present study confirmed previous observations by others of a progression from G0 through G1 and S phase to G2/mitosis during the first 3 d in culture. It was also found that on subsequent days stimulated cells, before their return to G0, remained stationary in a state in which they contained the G0 complement of DNA and approximately twice the G0 complement of RNA. Cell-cycle manipulation with vinblastine and 5-bromo-2-deoxyuridine (BUdR) revealed that previous passage through both S phase and mitosis was required for entry into this newly observed late phase. In addition, there was high correlation (r = 0.973, P less than 0.001) between the number of cells in the late phase and measured [3H]thymidine uptake. It therefore appears that, in this system, stimulated cells remain in a distinct cell-cycle phase for a number of hours before their return to the resting state.

scholarly journals Deferoxamine: a reversible S-phase inhibitor of human lymphocyte proliferation

Blood ◽  
1984 ◽  
Vol 64 (3) ◽  
pp. 748-753 ◽  
Author(s):  
HM Lederman ◽  
A Cohen ◽  
JW Lee ◽  
MH Freedman ◽  
EW Gelfand
Keyword(s):  
Ribonucleotide Reductase ◽  
Lymphocyte Proliferation ◽  
Potent Inhibitor ◽  
Reductase Activity ◽  
S Phase ◽  
Ferric Ion ◽  
Inhibitory Effects ◽  
Ribonucleotide Reductase Activity ◽  
B And T Lymphocytes

Deferoxamine is widely used therapeutically as a chelator of ferric ion in disorders of iron overload. This study demonstrates that this drug is a potent inhibitor of DNA synthesis by human B and T lymphocytes in vitro, but has relatively little effect on the synthesis of RNA and protein. The inhibitory effects of deferoxamine are completely reversible by washing or by adding stoichiometric amounts of Fe3+. Micromolar concentrations of deferoxamine decrease intracellular levels of deoxyribonucleoside triphosphates, which is similar to the effects of hydroxyurea. The binding of iron by deferoxamine likely causes an inhibition of ribonucleotide reductase activity, thereby preventing cells from completing the S phase of the cell proliferation cycle. As a reversible and nontoxic S-phase inhibitor, it may have important experimental and therapeutic applications.

Purine and pyrimidine analogues irreversibly prevent passage of lymphocytes from the G1 to the S phase of the cell cycle

1984 ◽  
Vol 62 (5) ◽  
pp. 280-287 ◽  
Author(s):  
Christine E. Boumah ◽  
George Setterfield ◽  
J. Gordin Kaplan
Keyword(s):  
Cell Cycle ◽  
Human Lymphocytes ◽  
S Phase ◽  
Inhibition Of Proliferation ◽  
Dna And Rna ◽  
Pyrimidine Analogue ◽  
Dna And Rna Synthesis ◽  
Irreversible Effects ◽  
Excess Thymidine ◽  
Irreversible Effect

Six-hour pulses of the purine analogue 8-azaguanine (8-AG) and the pyrimidine analogue 5-fluorouracil (5-FU) produced a novel irreversible effect on mouse and human lymphocytes. Cells treated with these analogues early during culture with concanavalin A and then washed in presence of excess natural base could pass normally through the various stages of blast formation (e.g., increased K+ transport, increase in nuclear and cytoplasmic volume, disaggregation of chromatin), but showed a severe inhibition of DNA synthesis when this was measured by [3H]thymidine incorporation at 48 h of culture; this was true irrespective of whether the 6-h pulse with analogue occurred at 0, 12, or 24 h of culture in the presence of mitogen. The analogue 6-mercaptopurine, which strongly inhibited DNA and RNA synthesis while present in the medium, had no irreversible effects, unlike 5-FU and 8-AG. The persistence of the effects of 5-FU in presence of excess thymidine in the medium suggested that inactivation of thymidylate synthetase was not responsible for the inhibition observed here. The effect was expressed in the presence or absence of protein synthesis; therefore, the observed inhibition of proliferation was not due to synthesis of a toxic protein, but to an effect on the formation or function of the DNA synthesizing system and (or) on its template, thus preventing the cells from passing from the G1to the S phase of the cell cycle.

scholarly journals Amiloride added together with bumetanide completely blocks mouse 3T3-cell exit from G0/G1-phase and entry into S-phase

1986 ◽  
Vol 239 (3) ◽  
pp. 745-750 ◽  
Author(s):  
R Panet ◽  
D Snyder ◽  
H Atlan
Keyword(s):  
Cell Cycle ◽  
Growth Factors ◽  
Dna Synthesis ◽  
Serum Insulin ◽  
S Phase ◽  
G1 Phase ◽  
G1 Arrest ◽  
Inhibitory Effects ◽  
Cell Transition ◽  
Mitogenic Signal

In this study we tested the hypothesis that stimulation of univalent-cation fluxes which follow the addition of growth factors are required for cell transition through the G1-phase of the cell cycle. The effect of two drugs, amiloride and bumetanide, were tested on exit of BALB/c 3T3 cells from G0/G1-phase and entry into S-phase (DNA synthesis). Amiloride, an inhibitor of the Na+/H+ antiport, only partially inhibited DNA synthesis induced by serum. Bumetanide, an inhibitor of the Na+/K+ co-transport, only slightly suppressed DNA synthesis by itself, but when added together with amiloride completely blocked cell transition through G1 and entry into S-phase. Similar inhibitory effects of the two drugs were found on the induction of ornithine decarboxylase (ODC) (a marker of mid-G1-phase) in synchronized cells stimulated by either partially purified fibroblast growth factor (FGF) or serum. To test this hypothesis further, cells arrested in G0/G1 were stimulated by serum, insulin or FGF. All induced similar elevations of cellular K+ content during the early G1-phase of the cell cycle. However, serum and FGF, but not insulin, released the cells from the G0/G1 arrest, as measured by ODC enzyme induction. This result implies that the increase in cellular K+ content may be necessary but not sufficient for induction of early events during the G1-phase. The synergistic inhibitory effects of amiloride and bumetanide on the two activities stimulated by serum growth factors, namely ODC induction (mid-G1) and thymidine incorporation into DNA (S-phase), suggested that the amiloride-sensitive Na+/H+ antiport system together with the bumetanide-sensitive Na+/K+ transporter play a role in the mitogenic signal.

The comparison of epirubicin-treated MCF-7 mammosphere cells to the treated monolayer cells

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13542-e13542
Author(s):  
M. Huang ◽  
F. Zhang ◽  
Y. Xu ◽  
H. Wang ◽  
S. Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
S Phase ◽  
G1 Phase ◽  
Cell Cycle Distribution ◽  
Inhibitory Effects ◽  
Lower Effect ◽  
G2 Phase ◽  
Cell Inhibition ◽  
Mcf 7

e13542 Objective: To explore the different effects of epirubicin on the MCF-7 mammosphere cells and the monolayer cells. Methods: MCF-7 cells were cultured in suspension to generate primary mammospheres. The inhibitory effects of epirubicin on MCF-7 mammosphere cells and the monolayer cells by were measured by MTT assay. The change of CD44+CD24- expression and cell cycle distribution in MCF-7 mammosphere cells and the monolayer cells under epirubicin condition was analyzed by flow cytometry. Results: The cell inhibition was lower in MCF-7 mammosphere cells than that in the monolayer cells when induced by the same concentration of epirubicin (>100 ng/ml),(P<0.01). The CD44+CD24- expression was significantly higher in MCF-7 mammosphere cells than that in the monolayer cells under 400 ng/μl epirubicin for 72 h, (22.8% ± 4.8% Vs 3.3% ± 0.8%),(P<0.01). The cell cycle indicated that MCF-7 mammosphere cells had higher proportion of G0/G1 phase than the monolayer cells, (74.33% ± 3.20% Vs 53.40% ± 3.45%) (P<0.01). Epirubicin had little effect on the G0/G1 phase of MCF-7 mammosphere cells and the monolayer cells, but the S phase and G2 phase was not the case. Conclusion: Epirubicin had lower inhibitory effects on MCF-7 mammosphere cells and it can be used to enrich breast cancer stem cell. Epirubicin had lower effect on the G0/G1 phase of MCF-7 mammosphere cells as compared with control. No significant financial relationships to disclose.

Tentacle morphogenesis in hydra. II. Formation of a complex between a sensory nerve cell and a battery cell

Development ◽  
1990 ◽  
Vol 109 (4) ◽  
pp. 897-904 ◽  
Author(s):  
E. Hobmayer ◽  
T.W. Holstein ◽  
C.N. David
Keyword(s):  
Cell Cycle ◽  
Monoclonal Antibody ◽  
Nerve Cell ◽  
Interstitial Cell ◽  
Sensory Nerve ◽  
S Phase ◽  
Nerve Cells ◽  
Battery Cell ◽  
Head Activator ◽  
Hydra Magnipapillata

Differentiation of sensory nerve cells in tentacles of Hydra magnipapillata was investigated using the monoclonal antibody NV1. NV1+ sensory nerve cells form specific complexes with battery cells in tentacles. NV1+ cells can only be formed by differentiation from interstitial cell precursors. These precursors complete a terminal cell cycle in the distal gastric region at the base of tentacles; differentiation from the S/G2 boundary to expression of the NV1 antigen requires 30h. During this time, precursors move from the distal gastric region into the tentacles, differentiate to morphologically fully formed nerve cells and then begin expressing NV1 antigen. The neuropeptide head activator stimulates NV1+ differentiation in S-phase of the precursor's cell cycle.

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