scholarly journals Granulocyte‐Macrophage Colony‐Stimulating Factor Induces Modest Increases in Plasma Human Immunodeficiency Virus (HIV) Type 1 RNA Levels and CD4+Lymphocyte Counts in Patients with Uncontrolled HIV Infection

2003 ◽  
Vol 188 (12) ◽  
pp. 1804-1814 ◽  
Author(s):  
Jeffrey M. Jacobson ◽  
Michael M. Lederman ◽  
John Spritzler ◽  
Hernan Valdez ◽  
Pablo Tebas ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Colony Stimulating Factor ◽  
Immunodeficiency Virus ◽  
Macrophage Colony Stimulating Factor ◽  
Hiv Type 1 ◽  
Cd4 Lymphocyte ◽  
Macrophage Colony ◽  
Stimulating Factor

scholarly journals Macrophage colony-stimulating factor enhances the susceptibility of macrophages to infection by human immunodeficiency virus and reduces the activity of compounds that inhibit virus binding

Blood ◽  
1994 ◽  
Vol 84 (10) ◽  
pp. 3405-3412 ◽  
Author(s):  
A Bergamini ◽  
CF Perno ◽  
L Dini ◽  
M Capozzi ◽  
CD Pesce ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Dextran Sulfate ◽  
Colony Stimulating Factor ◽  
Immunodeficiency Virus ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Anti Hiv ◽  
Stimulating Factor ◽  
Soluble Cd4

Abstract The effects of macrophage colony-stimulating factor (M-CSF) on CD4 receptor expression, susceptibility to human immunodeficiency virus type 1 (HIV) infection, and anti-HIV activity of dextran sulfate and soluble-CD4 were studied in cultured, human primary macrophages. M-CSF stimulated macrophage cells to express the CD4 receptor, and this resulted in an increase of both the number of CD4+ cells and the density of the receptor on the cell surface. M-CSF also significantly enhanced the susceptibility of macrophage cells to HIV infection. Interestingly, the anti-HIV activity of dextran sulfate and soluble-CD4 (two compounds that interfere with HIV-CD4 binding with different mechanisms) was reduced 100-fold and fivefold, respectively, in M-CSF- treated macrophages. Human blood concentrations of M-CSF are reported to be similar to those used in this work (1,000 U/mL); thus, it is conceivable that also in vivo this cytokine may modify the susceptibility of macrophages to HIV and the ability of dextran sulfate and soluble CD4 to inhibit HIV replication. These results suggest that the in vitro study in M-CSF-treated macrophages of promising drugs inhibitors of HIV-CD4 binding could provide further insights into the potential efficacy of these compounds in patients.

scholarly journals Macrophage colony-stimulating factor enhances the susceptibility of macrophages to infection by human immunodeficiency virus and reduces the activity of compounds that inhibit virus binding

Blood ◽  
1994 ◽  
Vol 84 (10) ◽  
pp. 3405-3412 ◽  
Author(s):  
A Bergamini ◽  
CF Perno ◽  
L Dini ◽  
M Capozzi ◽  
CD Pesce ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Dextran Sulfate ◽  
Colony Stimulating Factor ◽  
Immunodeficiency Virus ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Anti Hiv ◽  
Stimulating Factor ◽  
Soluble Cd4

The effects of macrophage colony-stimulating factor (M-CSF) on CD4 receptor expression, susceptibility to human immunodeficiency virus type 1 (HIV) infection, and anti-HIV activity of dextran sulfate and soluble-CD4 were studied in cultured, human primary macrophages. M-CSF stimulated macrophage cells to express the CD4 receptor, and this resulted in an increase of both the number of CD4+ cells and the density of the receptor on the cell surface. M-CSF also significantly enhanced the susceptibility of macrophage cells to HIV infection. Interestingly, the anti-HIV activity of dextran sulfate and soluble-CD4 (two compounds that interfere with HIV-CD4 binding with different mechanisms) was reduced 100-fold and fivefold, respectively, in M-CSF- treated macrophages. Human blood concentrations of M-CSF are reported to be similar to those used in this work (1,000 U/mL); thus, it is conceivable that also in vivo this cytokine may modify the susceptibility of macrophages to HIV and the ability of dextran sulfate and soluble CD4 to inhibit HIV replication. These results suggest that the in vitro study in M-CSF-treated macrophages of promising drugs inhibitors of HIV-CD4 binding could provide further insights into the potential efficacy of these compounds in patients.

scholarly journals Human Immunodeficiency Virus Type 1 Infection Inhibits Granulocyte-Macrophage Colony-Stimulating Factor-Induced Activation of STAT5A in Human Monocyte-Derived Macrophages

2003 ◽  
Vol 77 (23) ◽  
pp. 12630-12638 ◽  
Author(s):  
Tammra J. Warby ◽  
Suzanne M. Crowe ◽  
Anthony Jaworowski
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Monocyte ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Immunodeficiency Virus ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infects cells of the monocyte/macrophage lineage. While infection of macrophages by HIV-1 is generally not cytopathic, it does impair macrophage function. In this study, we examined the effect of HIV-1 infection on intracellular signaling in human monocyte-derived macrophages (MDM) stimulated with the growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF is an important growth factor for cells of both the macrophage and granulocyte lineages and enhances effector functions of these cells via the heterodimeric GM-CSF receptor (GM-CSFR). A major pathway which mediates the effects of GM-CSF on macrophages involves activation of the latent transcription factor STAT5A via a Janus kinase 2 (JAK2)-dependent pathway. We demonstrate that GM-CSF-induced activation of STAT5A is inhibited in MDM after infection in vitro with the laboratory-adapted R5 strain of HIV-1, HIV-1Ba-L, but not after infection with adenovirus. HIV-1 infection of MDM did not decrease the STAT5A or JAK2 mRNA level or STAT5A protein level or result in increased constitutive activation of STAT5A. Surface expression of either the α-chain or common βc-chain of GM-CSFR was also unaffected. We conclude that HIV-1 inhibits GM-CSF activation of STAT5A without affecting expression of the known components of the signaling pathway. These data provide further evidence of disruption of cellular signaling pathways after HIV-1 infection, which may contribute to immune dysfunction and HIV-1 pathogenesis.

scholarly journals Subcutaneous recombinant granulocyte-macrophage colony-stimulating factor used as a single agent and in an alternating regimen with azidothymidine in leukopenic patients with severe human immunodeficiency virus infection [see comments]

Blood ◽  
1990 ◽  
Vol 76 (3) ◽  
pp. 463-472 ◽  
Author(s):  
JM Pluda ◽  
R Yarchoan ◽  
PD Smith ◽  
N McAtee ◽  
LE Shay ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Geometric Mean ◽  
Hematologic Toxicity ◽  
Colony Stimulating Factor ◽  
Immunodeficiency Virus ◽  
P24 Antigen ◽  
Macrophage Colony Stimulating Factor ◽  
The Mean ◽  
Macrophage Colony ◽  
Stimulating Factor

We investigated the effects of recombinant human granulocyte-macrophage colony-stimulating factor (rGM-CSF) administered by the subcutaneous route, first alone and then alternating with azidothymidine (AZT), in leukopenic patients with severe human immunodeficiency virus (HIV) infection. Ten patients with acquired immunodeficiency syndrome (AIDS) or related disorders, five of whom could not tolerate conventional doses of AZT, were administered rGM-CSF subcutaneously for 12 days. They then were administered an alternating regimen using AZT for 1 week, followed by 5 days of subcutaneous rGM-CSF and 2 days without any medication. During the initial 12 days of GM-CSF administration, there was an increase in the mean white blood cell (WBC) value. In addition, rGM-CSF stimulated circulating monocytes as evidenced by an increase in superoxide anion production and expression of surface HLA-DR antigen. However, at the same time rGM-CSF increased the serum HIV p24 antigen in each of the six evaluable patients from 189 x/divided by 2.02 pg/mL (geometric mean x/divided by SEM) at entry to 375 x/divided by 2.11 pg/mL (P less than .05). During the subsequent period of alternating AZT and rGM-CSF treatment, serum HIV p24 antigen fell below the day 14 value in most patients, particularly after the weeks of AZT administration. The mean T4 cell value increased in patients who had not previously received AZT, but generally did not change in those who had prior AZT exposure. Hematologic toxicity appeared to be somewhat reduced compared with continuous full-dose AZT therapy, and two patients with previous AZT hematologic toxicity tolerated this alternating regimen for 25 weeks. Additional regimens simultaneously combining these two agents are worth exploring.

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