Molecular Mechanisms of Apoptosis Induced by an Immunomodulating Peptide on Human Monocytes

2000 ◽  
Vol 379 (2) ◽  
pp. 353-362 ◽  
Author(s):  
Juan A. Osés-Prieto ◽  
Natalia López-Moratalla ◽  
Esteban Santiago ◽  
Jean P. Jaffrézou ◽  
Maria J. López-Zabalza
Keyword(s):  
Molecular Mechanisms ◽  
Human Monocytes ◽  
Immunomodulating Peptide

Alteration of Actin Organization by Jaspamide Inhibits Ruffling, but not Phagocytosis or Oxidative Burst, in HL-60 Cells and Human Monocytes

Blood ◽  
1999 ◽  
Vol 93 (11) ◽  
pp. 3994-4005 ◽  
Author(s):  
Ina Fabian ◽  
Drora Halperin ◽  
Smadar Lefter ◽  
Leonid Mittelman ◽  
Rom T. Altstock ◽  
...  
Keyword(s):  
Oxidative Burst ◽  
Phagocytic Activity ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Cyclic Peptide ◽  
De Novo ◽  
Human Monocytes ◽  
Actin Organization ◽  
Fibrous Network ◽  
Intracellular Movement

Abstract Jaspamide, a naturally occurring cyclic peptide isolated from the marine sponge Hemiastrella minor, has fungicidal and growth-inhibiting activities. Exposure of promyelocytic HL-60 cells and human monocytes to jaspamide induces a dramatic reorganization of actin from a typical fibrous network to focal aggregates. HL-60 cells exposed to 5 × 10−8 mol/L or 10−7 mol/L jaspamide exhibited a reduced proliferation rate. In addition, 10−7mol/L jaspamide induced maturation of HL-60 cells as indicated by the appearance of a lobulated nucleus in 55% ± 5% of the cells and immunophenotypic maturation of the leukemia cells (upregulation of CD16 and CD14 B antigens). Further characterization has shown that F-actin is aggregated both in HL-60 cells and in human monocytes exposed to 10−7 mol/L jaspamide. Well-spread cultured human monocytes contracted and adopted round shapes after treatment with jaspamide. Moreover, a dose-dependent increase in both total actin and de novo synthesized portions of the soluble actin was observed in jaspamide-treated HL-60 cells. Jaspamide treatment inhibits ruffling and intracellular movement in HL-60 cells and monocytes, but does not affect phagocytic activity or respiratory burst activity. The consequential effects of jaspamide-induced actin reorganization on ruffling, versus its negligible effect on phagocytosis and oxidative burst, may shed light on molecular mechanisms of actin involvement in these processes. Jaspamide disrupts the actin cytoskeleton of normal and malignant mammalian cells with no significant effect on phagocytic activity and may, therefore, be considered as a novel therapeutic agent.

Specific translocation of tuftsin (Thr-Lys-Pro-Arg), a natural immunomodulating peptide, into the nuclei of human monocytes

1989 ◽  
Vol 159 (3) ◽  
pp. 1147-1153 ◽  
Author(s):  
Jyoti R. Wagle ◽  
Allen T. Ansevin ◽  
Steven E. Dessens ◽  
Kenji Nishioka
Keyword(s):  
Human Monocytes ◽  
Immunomodulating Peptide

Alteration of Actin Organization by Jaspamide Inhibits Ruffling, but not Phagocytosis or Oxidative Burst, in HL-60 Cells and Human Monocytes

Blood ◽  
1999 ◽  
Vol 93 (11) ◽  
pp. 3994-4005
Author(s):  
Ina Fabian ◽  
Drora Halperin ◽  
Smadar Lefter ◽  
Leonid Mittelman ◽  
Rom T. Altstock ◽  
...  
Keyword(s):  
Oxidative Burst ◽  
Phagocytic Activity ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Cyclic Peptide ◽  
De Novo ◽  
Human Monocytes ◽  
Actin Organization ◽  
Fibrous Network ◽  
Intracellular Movement

Jaspamide, a naturally occurring cyclic peptide isolated from the marine sponge Hemiastrella minor, has fungicidal and growth-inhibiting activities. Exposure of promyelocytic HL-60 cells and human monocytes to jaspamide induces a dramatic reorganization of actin from a typical fibrous network to focal aggregates. HL-60 cells exposed to 5 × 10−8 mol/L or 10−7 mol/L jaspamide exhibited a reduced proliferation rate. In addition, 10−7mol/L jaspamide induced maturation of HL-60 cells as indicated by the appearance of a lobulated nucleus in 55% ± 5% of the cells and immunophenotypic maturation of the leukemia cells (upregulation of CD16 and CD14 B antigens). Further characterization has shown that F-actin is aggregated both in HL-60 cells and in human monocytes exposed to 10−7 mol/L jaspamide. Well-spread cultured human monocytes contracted and adopted round shapes after treatment with jaspamide. Moreover, a dose-dependent increase in both total actin and de novo synthesized portions of the soluble actin was observed in jaspamide-treated HL-60 cells. Jaspamide treatment inhibits ruffling and intracellular movement in HL-60 cells and monocytes, but does not affect phagocytic activity or respiratory burst activity. The consequential effects of jaspamide-induced actin reorganization on ruffling, versus its negligible effect on phagocytosis and oxidative burst, may shed light on molecular mechanisms of actin involvement in these processes. Jaspamide disrupts the actin cytoskeleton of normal and malignant mammalian cells with no significant effect on phagocytic activity and may, therefore, be considered as a novel therapeutic agent.

Abstract 15252: Ischemic-Trained Monocytes Improve Arteriogenesis During Hindlimb Ischemia

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Gustavo Falero-Diaz ◽  
Catarina d Barboza ◽  
Felipe Pires ◽  
Roberto I Vazquez-Padron ◽  
Omaida C Velazquez ◽  
...  
Keyword(s):  
Blood Flow ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Local Effect ◽  
Human Monocytes ◽  
Hindlimb Ischemia ◽  
Artery Ligation ◽  
Trained Immunity ◽  
Major Player ◽  
Before And After

Introduction: Recent studies have shown that innate response can build immunological memory. This process called “trained immunity” is an epigenetic reprogramming of the monocytes driven by a metabolism shift towards glycolysis. Hypothesis: Since HIF-1a is a major player in monocytes activation and also targets some epigenetic enzymes, we hypothesize that hypoxia/ischemia can lead to “trained immunity” improving arteriogenesis in a mouse model of hindlimb ischemia. Methods: Mice subjected to a unilateral single ischemia insult for 24hours (24h group: femoral artery ligation for 24 h) or by ischemia reperfusion cycles (Cycle group: ischemia-reperfusion in 4 cycles of 5 minutes) or non-ischemia (sham group), were used as donors in the monocyte transfer experiment. Recipient mice underwent to permanent hindlimb ischemia one day prior the tail vein injection of bone marrow (BM) monocytes from the ischemic leg. Laser Doppler assessed blood flow recovery before and after hindlimb ischemia. Arteriogenesis was quantified on recipient mice by assessing the diameter of gracilis collaterals. A 24h group monocytes from ischemia and non-ischemia leg was used as donors to test the systemic vs. local effect of the ischemic-trained monocytes. Lin- cells were used as a control. Cultured human monocytes were subjected to 24h hypoxia and gene expression for epigenetic enzymes was performed by real time rt-PCR Results: Blood flow recovery in recipients who received ischemic-trained monocytes (24h and cycle) improved overtime compared to sham. Arteriogenesis was significant greater in 24h group compared to sham. Surprisingly, the improvement in blood flow recovery was abolished using combined monocytes from ischemic and non-sichemic, suggesting that ischemia training has a local effect in the monocytes. The Lin- experiment confirmed that the ischemia training is monocyte specific. Moreover, hypoxia regulated epigenetic enzymes responsible for histones methylation in human monocytes. Conclusions: Monocytes can be trained by previous ischemia/hypoxia insult and improve arteriogenesis during hindlimb ischemia. The molecular mechanisms that lead the trained immunity by hypoxia still unknown, however epigenetic modifications might play a role in this process.

Signaling Pathway Triggered by a Short Immunomodulating Peptide on Human Monocytes

1997 ◽  
Vol 338 (2) ◽  
pp. 136-142 ◽  
Author(s):  
Marı́a J. López-Zabalza ◽  
Silvia Martı́nez-Lausı́n ◽  
M.Teresa Bengoechea-Alonso ◽  
Natalia López-Moratalla ◽  
Alvaro González ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Human Monocytes ◽  
Immunomodulating Peptide

Four SR Proteins Play Opposing Roles in the Regulated Biosynthesis of Tissue Factor in Human Monocytic Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2128-2128
Author(s):  
Sajiv Chandradas ◽  
Gintaras Deikus ◽  
Jonathan G. Tardos ◽  
David H Bechhofer ◽  
Vladimir Y Bogdanov
Keyword(s):  
Complex Formation ◽  
Tissue Factor ◽  
Binding Sites ◽  
Molecular Mechanisms ◽  
Conflicts Of Interest ◽  
Sr Proteins ◽  
Human Monocytes ◽  
Wild Type ◽  
Binding Motifs ◽  
Rna Probes

Abstract Abstract 2128 Poster Board II-105 Background. Circulating Tissue Factor (TF) is a major contributor to the etiology of thrombotic disorders. Blood monocytes are the primary source of circulating TF, which they express in two forms: full length TF (flTF), a transmembrane surface protein, and alternatively spliced TF (asTF), a secreted soluble protein. The presence or absence of the internal cassette exon 5 in the TF mRNA determines whether the encoded protein is flTF or asTF, respectively. While the procoagulant potential of flTF vastly exceeds that of asTF when assessed using conventional static assays, asTF exhibits unique angiogenic properties distinct from flTF. Investigation of the molecular mechanisms governing TF exon 5 processing is of much interest as it may afford novel approaches to modulate monocyte-mediated blood thrombogenicity as well as monocyte-induced angiogenesis. Using a splicing reporter system developed to study the processing of TF pre-mRNA, we previously determined that SR proteins ASF/SF2 and SRp55 are vital for TF exon 5 inclusion in human monocytes (Tardos et al, J Thromb Haemost 6:877-884, 2008). In the course of more recent experiments, we found that in contrast to ASF/SF2 and SRp55, two other SR proteins – SC35 and SRp40 – appear to promote exclusion of this variable exon: weakening of the binding motifs for SC35 (sites 33 and 81) and SRp40 (site 44), whose positions in exon 5 overlap with the binding sites for ASF/SF2 and SRp55, results in the decrease of the splicing event unique to asTF. The competition of these four SR proteins for binding to their overlapping binding sites may thus play a role in the maintenance of the asTF / flTF ratio; however, a physical association of SC35 and SRp40 with their putative sites in exon 5 was not demonstrated. Objective. To determine whether SC35 and/or SRp40 physically associate with their putative binding sites. Results. To evaluate interaction of the SR proteins SC35 and SRp40 with their putative binding sites in TF exon 5, we employed RNA mobility shift assay methodology using freshly prepared nuclear extracts of THP-1 cells, a monocytic cell line, and in vitro transcribed, uniformly labeled RNA probes comprising the two regions of interest – one spanning SC35 site 33 and SRp40 site 44, and the other spanning the SC35 site 81. As expected, these RNA probes yielded reproducible band shift products, confirming RNA-protein complex formation. We then developed three counterpart mutant RNA probes in which the SC35 and SRp40 binding motifs were selectively weakened by targeted site-directed mutagenesis, and performed RNA gel shift assays alongside the corresponding wild-type probes. Each mutant probe exhibited a significantly weaker interaction with the SR proteins compared to its wild-type counterpart: the SC35 site 33 mutant probe produced a 31.1% reduction in complex formation relative to wild-type (p = 0.011), the SRp40 site 44 mutant probe also produced a 31.1% reduction in complex formation relative to wild-type (p = 0.0001), and the SC35 site 81 mutant probe produced a 33.0% reduction in complex formation relative to wild-type (p = 0.0151). Conclusions. We show for the first time that SR proteins SC35 and SRp40 physically associate with functional binding sites within TF exon 5. The SC35 and SRp40 binding sites overlap with the binding sites for ASF/SF2 and SRp55, the SR proteins that promote exon 5 inclusion. The opposing effects of distinct SR proteins on TF exon 5 processing reveal a heretofore unknown mechanism governing regulated TF biosynthesis. Further studies of SR protein-mediated effects on the TF profile of human monocytes are likely to aid in the development of novel therapeutic strategies aimed at selective targeting of biologically distinct TF forms. Disclosures: No relevant conflicts of interest to declare.

Molecular mechanisms of IL-4 effect on HIV expression in promonocytic cell lines and primary human monocytes

1994 ◽  
Vol 56 (3) ◽  
pp. 335-339 ◽  
Author(s):  
Hassan Naif ◽  
Michael Ho-Shon ◽  
Joon Chang ◽  
Anthony L. Cunningham
Keyword(s):  
Cell Lines ◽  
Molecular Mechanisms ◽  
Human Monocytes

scholarly journals Iκκ Mediates NF-κB Activation in Human Immunodeficiency Virus-Infected Cells

1999 ◽  
Vol 73 (5) ◽  
pp. 3893-3903 ◽  
Author(s):  
Susana Asin ◽  
Julie A. Taylor ◽  
Sergey Trushin ◽  
Gary Bren ◽  
Carlos V. Paya
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Viral Persistence ◽  
Human Monocytes ◽  
Regulatory Domains ◽  
Immunodeficiency Virus ◽  
Monocytes And Macrophages ◽  
Infected Cells

ABSTRACT Human monocytes and macrophages are persistent reservoirs of human immunodeficiency virus (HIV) type-1. Persistent HIV infection of these cells results in increased levels of NF-κB in the nucleus secondary to increased IκBα, IκBβ, and IκBɛ degradation, a mechanism postulated to regulate viral persistence. To characterize the molecular mechanisms regulating HIV-mediated degradation of IκB, we have sought to identify the regulatory domains of IκBα targeted by HIV infection. Using monocytic cells stably expressing different transdominant molecules of IκBα, we determined that persistent HIV infection of these cells targets the NH2 but not the COOH terminus of IκBα. Further analysis demonstrated that phosphorylation at S32 and S36 is necessary for HIV-dependent IκBα degradation and NF-κB activation. Of the putative N-terminal IκBα kinases, we demonstrated that the Iκκ complex, but not p90 rsk , is activated by HIV infection and mediates HIV-dependent NF-κB activation. Analysis of viral replication in cells that constitutively express IκBα negative transdominant molecules demonstrated a lack of correlation between virus-induced NF-κB (p65/p50) nuclear translocation and degree of viral persistence in human monocytes.

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