Recombinant human granulocyte-colony stimulating factor and recombinant human macrophage colony stimulating factor synergize in vivo to enhance proliferation of granulocyte-macrophage, erythroid, and multipotential progenitor cells in mice

1988 ◽  
Vol 38 (2) ◽  
pp. 127-136 ◽  
Author(s):  
Hal E. Broxmeyer ◽  
Douglas E. Williams ◽  
Scott Cooper ◽  
Giao Hangoc ◽  
Peter Ralph
Blood ◽  
1990 ◽  
Vol 75 (4) ◽  
pp. 846-850 ◽  
Author(s):  
TR Ulich ◽  
J del Castillo ◽  
LR Watson ◽  
SM Yin ◽  
MB Garnick

Abstract Macrophage colony-stimulating factor (recombinant human M-CSF) given as a single intravenous injection to Lewis rats induces a dose-dependent peripheral monocytosis, neutrophilia, and lymphopenia. The monocytosis peaks at 28 to 32 hours with a seven- to eightfold increase in the number of circulating monocytes and promonocytes. The peripheral monocytosis is accompanied by a slight increase in marrow blasts, promonocytes, and monocytes. A monocytopenia reaching a nadir at 15 minutes precedes the monocytosis, suggesting that M-CSF activates circulating monocytes and causes intravascular margination. The M-CSF- induced neutrophilia and lymphopenia are relatively mild in magnitude, are observed between 2 and 16 hours after injection, and are no longer evident at later time-points. The monocytosis was at least partially inhibited by dexamethasone. M-CSF-induced monocytosis most likely reflects a direct effect of M-CSF on marrow monocyte precursor proliferation, maturation, and release, whereas the neutrophilia and lymphopenia may reflect indirect effects mediated by the known ability of M-CSF to cause the release of other cytokines.


2019 ◽  
Vol 20 (20) ◽  
pp. 5113 ◽  
Author(s):  
Janice A. Layhadi ◽  
Samuel J. Fountain

Tissues differentially secrete multiple colony stimulating factors under conditions of homeostasis and inflammation, orientating recruited circulating monocytes to differentiate to macrophage with differing functional phenotypes. Here, we investigated ATP-evoked intracellular Ca2+ responses in human macrophage differentiated with macrophage colony-stimulating factor (M-CSF). Extracellular ATP evoked (EC50 13.3 ± 1.4 μM) robust biphasic intracellular Ca2+ responses that showed a dependency on both metabotropic (P2Y) and ionotropic (P2X) receptors. qRT-PCR and immunocytochemistry revealed the expression of P2Y1, P2Y2, P2Y6, P2Y11, P2Y13, P2X1, P2X4, P2X5, and P2X7. Pharmacological analysis revealed contribution of only P2X4 and P2Y11 to the Ca2+ response evoked by maximal ATP concentrations (100 µM). This study reveals the contribution of P2X4 and P2Y11 receptor activation to ATP-evoked intracellular Ca2+ responses, and makes comparison with macrophage differentiated using granulocyte colony-stimulating factor (GM-CSF).


Blood ◽  
1991 ◽  
Vol 78 (4) ◽  
pp. 967-974 ◽  
Author(s):  
N Sato ◽  
K Sawada ◽  
M Kannonji ◽  
T Tarumi ◽  
N Sakai ◽  
...  

Abstract To facilitate the investigation of the direct interaction between hematopoietic progenitors and colony-stimulating factors, we have developed a method to purify human marrow progenitor cells. Using density centrifugation, negative panning with concanavalin A coated plates, positive selection of CD34-positive cells with immunomagnetic microspheres, overnight adherence to a plastic dish, negative selection with a panel of monoclonal antibodies, and density centrifugation, human marrow progenitor cells were purified from 1.5% to 53.2%, a 42- fold purification, with a 4.8% yield. The purified cells consisted of 38% erythroid, 9% colony forming unit-granulocyte (CFU-G), 29% CFU- macrophage (CFU-M), 12% CFU-eosinophil/basophil (CFU-Eo/Ba), and 4% CFU- mix. The purified cells cultured in serum-free fibrin clots with recombinant human macrophage colony-stimulating factor (rM-CSF) for 14 days developed a pure population of CFU-M colonies. An appearance of CFU-M colonies was present after the addition of 1 U/mL of rM-CSF and the maximum stimulation was found at 100 U/mL. When the purified cells were cultured in serum-free medium with rM-CSF in a limiting dilution assay and the percentage of nonresponder wells for CFU-M colonies was plotted against cell concentration, serum-free cultures yielded a straight line through the origin, indicating that CFU-M development did not depend on accessory cells and that rM-CSF acted directly on the CFU- M.


1999 ◽  
Vol 17 (4) ◽  
pp. 1296-1296 ◽  
Author(s):  
Alberto Ballestrero ◽  
Fabio Ferrando ◽  
Anna Garuti ◽  
Palma Basta ◽  
Roberta Gonella ◽  
...  

PURPOSE: To compare the toxicity and effects on hematologic recovery and circulating progenitor cell mobilization of three cytokine regimens administered after high-dose cyclophosphamide (HD-CTX; 6 g/m2), given as the first step of a high-dose sequential chemotherapy. PATIENTS AND METHODS: Forty-eight patients with breast cancer or non-Hodgkin's lymphoma were randomized to receive granulocyte colony-stimulating factor (G-CSF) alone (arm 1), granulocyte-macrophage colony-stimulating factor (GM-CSF) alone (arm 2), or sequential interleukin-3 (IL-3) and GM-CSF (arm 3). Cytokines were administered as a single daily subcutaneous injection at a dose of 5 to 6 μg/kg/d. Progenitor cells were evaluated in peripheral blood as well as in apheretic product as both CD34+ cells and granulocyte-macrophage colony-forming units (CFU-GM). RESULTS: Neutrophil recovery was faster in arm 1 as compared with arms 2 and 3 (P < .0001); no significant differences were observed between arms 2 and 3. In arm 3, a moderate acceleration of platelet recovery was observed, but it was statistically significant only as compared with arm 1 (P = .028). The peak of CD34+ cells was hastened in a median of 2 days in arm 1 compared with arms 2 and 3 (P = .0002), whereas the median peak value of CD34+ cells and CFU-GM was similar in the three patient groups. Administration of IL-3 and GM-CSF resulted in more significant toxicity requiring pharmacologic treatment in 90% of patients. CONCLUSION: The three cytokine regimens administered after HD-CTX are comparably effective in reducing hematologic toxicity and mobilizing the hematopoietic progenitor cells. G-CSF accelerates leukocyte recovery and progenitor mobilization. Although G-CSF–treated patients have somewhat slower platelet recovery, they definitely have fewer side effects.


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