Granulocyte Colony-stimulating Factor Synergistically Augments 1,25-Dihydroxyvitamin D₃-Induced Monocytic Differentiation in Murine Bone Marrow Cell Cultures

Abstract

In a series of studies, we have reported that 1,25-dihydroxyvitamin D (3), a known stimulator of monocytic differentiation, primes bone marrow progenitor cells or promyelocytic HL-60 cells to the actions of several factors involved in both monocytic and granulocytic differentiation. In the present study, we have further examined the combinational effects of 1,25-dihydroxyvitamin D (3) and the other inducer of granulopoiesis, granulocyte colony-stimulating factor, on non-fractionated native murine bone-marrow cell culture. Over 6 days of treatment, human granulocyte colony-stimulating factor sustained cell viability, increased the size of small rounded non-adherent cells, and induced granulocytic differentiation, while 1,25-dihydroxyvitamin D (3) decreased cell viability, promoted the development of large adherent flattened cells, and upregulated some monocytic differentiation markers. Combining these two factors over 6 days synergistically upregulated phagocyte activity, membrane-bound interleukin-1alpha, NAD(P)H oxidase, monocytic Mac-1, and non-specific esterase. Similar effects were observed in successive treatment with granulocyte colony-stimulating factor followed by 1,25-dihydroxyvitamin D (3), but successive treatment in reverse order was somewhat less effective. No combinational treatment upregulated granulocytic lactate dehydrogenase, Gr-1, or chloroacetate esterase to as great an extent as was obtained with granulocyte colony-stimulating factor alone, indicating that granulocytic differentiation is attenuated by addition of 1,25-dihydroxyvitamin D (3). Therefore, in contrast to our previous data, the present findings suggest that granulocyte colony-stimulating factor synergistically augments 1,25-dihydroxyvitamin D (3)-induced monocytic differentiation in our murine bone-marrow cell cultures. Considering previously published data, we also suggest that these synergistic effects may be mainly due to the combination of two distinct effects such as the primary proliferative effects of granulocyte colony-stimulating factor on multipotent stem cells and the subsequent differentiative effects of 1,25-dihydroxyvitamin D (3) on proliferating cells.

Macrophages and Giant Cell Proliferation Associated with Bone Protein Synthesis and Calcification in the Trachea and Bronchi of Rabbits Intoxicated with Solanum glaucophyllum

“…The differentiation of monocytes to macrophages and their fusion to form giant cells, induced by the 1,25(OH) 2 D 3 , has been well documented experimentally. 1, 14, 15, 20, 21 The proliferation of macrophages and multinucleated giant cells in the present study could be the response of these cells to the action of the 1,25(OH) 2 D 3 present in S. glaucophyllum . Such action has been suggested in similar infiltrates in the muscle layer of the stomach of rabbits experimentally poisoned with the same plant 18 and in arteries and lungs of sheep with enzootic calcinosis induced by the calcinogenic plant Nierembergia veitchii .…”

“…The participation of 1,25(OH) 2 D 3 in the differentiation of monocytes to macrophages and fusion to form multinucleated giant cells has been extensively studied. 1, 11, 14, 15, 21 Infiltration of macrophages and multinucleated giant cells in lung, arteries, stomach, and heart were described in natural and experimental calcinosis induced by calcinogenic plants 2– 4, 18, 28, 37, 41 that contain high levels of 1,25(OH) 2 D 3 as a glycoside derivative. 40…”

Melatonin and Vitamin D Interfere with the Adipogenic Fate of Adipose-Derived Stem Cells

“…Vitamin D3 has a range of physiological functions in the body, the most important being the maintenance of the calcium and phosphorus balance [14] in osteoblasts, where it usually inhibits cellular proliferation and induces differentiation [15]. …”

Expressions of polypeptide: N-acetylgalactosaminyltransferase in leukemia cell lines during 1,25-dihydroxyvitamin D3 induced differentiation

“…In addition to its hormonal action on calcium metabolism, 1, 25(OH) 2 D3 has been known as an inducer of leukocyte differentiation, stimulating the differentiation of bone marrow progenitor cells or HL60 cells toward monocyte/macrophage lineage [20,21]. It was reported that 1,25(OH) 2 D3 also participated in the growth arrest, apoptosis or differentiation of other cancer cells, such as prostate and thyroid cancers [22,23].…”