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.

Granulocyte-macrophage colony-stimulating factor preferentially activates the 94-kD STAT5A and an 80-kD STAT5A isoform in human peripheral blood monocytes

Blood ◽  
1996 ◽  
Vol 88 (4) ◽  
pp. 1206-1214 ◽  
Author(s):  
RL Rosen ◽  
KD Winestock ◽  
G Chen ◽  
X Liu ◽  
L Hennighausen ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Human Peripheral Blood ◽  
Janus Kinase ◽  
Lower Molecular Weight ◽  
Colony Stimulating Factor ◽  
Enhancer Element ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Granulocyte-macrophage colony-stimulating factor (GM-CSF) induces immediate effects in monocytes by activation of the Janus kinase (JAK2) and STAT transcription factor (STAT5) pathway. Recent studies have identified homologues of STAT5, STAT5A, and STAT5B, as well as lower molecular weight variants of STAT5. To define the activation of the STAT5 homologues and lower molecular weight variant in human monocytes and monocytes differentiated into macrophages by culture in macrophage- CSF (M-CSF), we measured the GM-CSF induced tyrosine phosphorylation of STAT5A, STAT5B, and any lower molecular weight STAT5 isoforms. Freshly isolated monocytes expressed 94-kD STAT5A, 92-kD STAT5B, and an 80-kD STAT5A molecule. Whereas 94-kD STAT5A was clearly tyrosine phosphorylated and bound to the enhancer element, the gamma response region (GRR), of the Fc gamma RI gene, substantially less tyrosine phosphorylated STAT5B bound to the immobilized GRR element. Macrophages lost their ability to express the 80-kD STAT5A protein, but retained their ability to activate STAT5A. STAT5A-STAT5A homodimers and STAT5A- STAT5B heterodimers formed in response to GM-CSF. Therefore, activation of STAT5A predominates compared to STAT5B when assayed by direct immunoprecipitation and by evaluation of bound STATs to immobilized GRR. Selective activation of STAT5 homologues in addition to generation of lower molecular isoforms may provide specificity and control to genes expressed in response to cytokines such as GM-CSF.

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