Evidence that Granulocyte/Macrophage-Colony-Stimulating Factor and Interferon-γ Maintain the Viability of Human Peripheral Blood Monocytes in Part by Their Suppression of IL-10 Production

1995 ◽  
Vol 107 (1-3) ◽  
pp. 90-92 ◽  
Author(s):  
Michael K. Bach ◽  
John R. Brashler
Keyword(s):  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Interferon Γ ◽  
Colony Stimulating Factor ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Generation of Functional Human Dendritic Cells From Adherent Peripheral Blood Monocytes by CD40 Ligation in the Absence of Granulocyte-Macrophage Colony-Stimulating Factor

Blood ◽  
1998 ◽  
Vol 92 (11) ◽  
pp. 4238-4247 ◽  
Author(s):  
Peter Brossart ◽  
Frank Grünebach ◽  
Gernot Stuhler ◽  
Volker L. Reichardt ◽  
Robert Möhle ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Colony Stimulating Factor ◽  
Blood Monocytes ◽  
Rt Pcr ◽  
Cd40 Ligation ◽  
Peripheral Blood Monocytes ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Recently it has been shown that dendritic cells (DC) can develop from peripheral blood monocytes when grown in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). However, it is unclear whether DC can also develop from monocytes in absence of these cytokines. We therefore analyzed the effect of Flt-3 ligand (Flt3L) and of CD40 ligand on the development of human DC from blood monocytes in the absence of GM-CSF. Adherent peripheral blood mononuclear cells (PBMNC) were cultured in the presence of different cytokine combinations and analyzed for the expression of surface molecules and antigen presenting capacity. For functional analyses, cells were tested for their ability to stimulate allogeneic T lymphocytes in a mixed lymphocyte reaction (MLR), to present soluble antigens, and to induce primary HIV-peptide–specific cytotoxic T-cell (CTL) responses in vitro. Furthermore, expression of DC-CK1, a recently identified chemokine with specific expression in DC, and of IL-18 (IGIF), a growth and differentiation factor for Th 1 lymphocytes, was analyzed by reverse-transcription polymerase chain reaction (RT-PCR). In our study, Flt3L alone was not sufficient to generate DC and required addition of IL-4. DC generated with Flt3L and IL-4 underwent maturation after stimulation with tumor necrosis factor- (TNF-) or CD40L, characterized by CD83 expression, upregulation of MHC, adhesion, and costimulatory molecules as well as increased allogeneic proliferative response. In contrast, CD40 ligation alone promoted differentiation of adherent blood monocytes into functional DC in the absence of GM-CSF and IL-4. These cells displayed all phenotypic and functional characteristics of mature DC and were potent stimulatory cells in priming of major histocompatibility complex (MHC) class I–restricted CTL responses against an HIV-peptide, whereas their ability to present soluble protein antigens was reduced. Using a semiquantitative RT-PCR, DC-CK1 and IL-18 transcripts were detected in all generated DC populations, independent of growth factors used. Our findings provide further evidence for the importance of CD40-CD40L interaction for initiation and maintenance of T-cell responses and confirm the emerging concept that blood monocytes provide an additional source of DC depending on external stimuli.

Generation of Functional Human Dendritic Cells From Adherent Peripheral Blood Monocytes by CD40 Ligation in the Absence of Granulocyte-Macrophage Colony-Stimulating Factor

Blood ◽  
1998 ◽  
Vol 92 (11) ◽  
pp. 4238-4247 ◽  
Author(s):  
Peter Brossart ◽  
Frank Grünebach ◽  
Gernot Stuhler ◽  
Volker L. Reichardt ◽  
Robert Möhle ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Colony Stimulating Factor ◽  
Blood Monocytes ◽  
Rt Pcr ◽  
Cd40 Ligation ◽  
Peripheral Blood Monocytes ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Recently it has been shown that dendritic cells (DC) can develop from peripheral blood monocytes when grown in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). However, it is unclear whether DC can also develop from monocytes in absence of these cytokines. We therefore analyzed the effect of Flt-3 ligand (Flt3L) and of CD40 ligand on the development of human DC from blood monocytes in the absence of GM-CSF. Adherent peripheral blood mononuclear cells (PBMNC) were cultured in the presence of different cytokine combinations and analyzed for the expression of surface molecules and antigen presenting capacity. For functional analyses, cells were tested for their ability to stimulate allogeneic T lymphocytes in a mixed lymphocyte reaction (MLR), to present soluble antigens, and to induce primary HIV-peptide–specific cytotoxic T-cell (CTL) responses in vitro. Furthermore, expression of DC-CK1, a recently identified chemokine with specific expression in DC, and of IL-18 (IGIF), a growth and differentiation factor for Th 1 lymphocytes, was analyzed by reverse-transcription polymerase chain reaction (RT-PCR). In our study, Flt3L alone was not sufficient to generate DC and required addition of IL-4. DC generated with Flt3L and IL-4 underwent maturation after stimulation with tumor necrosis factor- (TNF-) or CD40L, characterized by CD83 expression, upregulation of MHC, adhesion, and costimulatory molecules as well as increased allogeneic proliferative response. In contrast, CD40 ligation alone promoted differentiation of adherent blood monocytes into functional DC in the absence of GM-CSF and IL-4. These cells displayed all phenotypic and functional characteristics of mature DC and were potent stimulatory cells in priming of major histocompatibility complex (MHC) class I–restricted CTL responses against an HIV-peptide, whereas their ability to present soluble protein antigens was reduced. Using a semiquantitative RT-PCR, DC-CK1 and IL-18 transcripts were detected in all generated DC populations, independent of growth factors used. Our findings provide further evidence for the importance of CD40-CD40L interaction for initiation and maintenance of T-cell responses and confirm the emerging concept that blood monocytes provide an additional source of DC depending on external stimuli.

scholarly journals Antibody-dependent antitumor cytotoxicity by human monocytes cultured with recombinant macrophage colony-stimulating factor. Induction of efficient antibody-mediated antitumor cytotoxicity not detected by isotope release assays.

1989 ◽  
Vol 170 (2) ◽  
pp. 511-526 ◽  
Author(s):  
D H Munn ◽  
N K Cheung
Keyword(s):  
Human Peripheral Blood ◽  
Neuroblastoma Cell ◽  
Colony Stimulating Factor ◽  
Blood Monocytes ◽  
Macrophage Colony Stimulating Factor ◽  
Activated Monocytes ◽  
Macrophage Colony ◽  
Neuroblastoma Cell Lines ◽  
Stimulating Factor

Macrophage colony-stimulating factor (M-CSF) is known to stimulate proliferation of monocyte/macrophage progenitors and enhance in vitro antitumor cytotoxicity by murine macrophages. In this paper we have shown that recombinant human M-CSF causes human peripheral blood monocytes to differentiate in culture into metabolically active macrophage-like cells. These cells mediate very efficient antibody-dependent cellular cytotoxicity (ADCC) against human melanoma and neuroblastoma cell lines in the presence of two murine IgG3 mAbs (3F8 and R24). They also mediate antibody-independent cytotoxicity (or cytostasis) to a lesser extent. Human serum had an inconsistent effect on ADCC, but often induced similar high levels of ADCC. Cytotoxicity was measured using a novel ELISA to detect surviving tumor cells after ADCC. Two conventional isotope-release assays (51Cr and [3H]TdR) underestimated or entirely failed to detect ADCC by M-CSF-activated monocytes. Optimal activation occurred with 100-300 U/ml of M-CSF, and required 9-11 d for completion. Most of the M-CSF cultured monocytes expressed the low-affinity Fc receptor (CD16). ADCC by cells of the monocyte/macrophage lineage using murine IgG3 mAbs may have significance for the immunotherapy of human malignancies.

Si-Jun-Zi-Tang Regulate Granulocyte Macrophage Colony-stimulating Factor Secretion by Human Peripheral Blood Mononuclear Cells

1996 ◽  
Vol 24 (01) ◽  
pp. 45-52 ◽  
Author(s):  
Jerming Tseng ◽  
Tsui-Li Li
Keyword(s):  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Suppressive Effect ◽  
Dependent Manner ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Dose Dependent ◽  
Stimulating Factor

Si-Jun-Zi-Tang is one of the widely used Chinese herbal medicines. In this study, human peripheral blood monocytes were treated in vitro with 50% hot ethanol extract of Si-Jun-Zi-Tang and its four major ingredients (Dangshen, Baizhu, Gancao and Fuling). The concentration of granulocyte-macrophage colony-stimulating factor (GM-CSP) in the culture supernatant at 3 hours and 18 hours were measured using an ELISA. Dangshen and Gancao significantly suppressed GM-CSP secretion in a dose-dependent manner. Baizhu showed no statistically significant effect on GM-CSP secretion 18 hours after in vitro drug-treatment. Fuling, by contrast, significantly augmented GM-CSP secretion in a dose dependent manner after 18 hours of drug treatment. Si-Jun-Zi-Tang showed a suppressive effect on GM-CSP secretion at 3 hours but significantly augmented GM-CSP secretion when the cells were treated with 8 mg/ml of the drug for 18 hours. The data suggested that Si-Jun-Zi-Tang might modulate hematopoiesis and immune response via regulating GM-CSP secretion, and the presence of Fuling in Si-Jun-Zi-Tang could counteract the suppressive effect of Dangshen and Gancao on GM-CSP secretion.

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