Interleukin-3 and interleukin-1 alpha allow earlier bone marrow progenitors to respond to human colony-stimulating factor 1

Abstract By using human bone marrow cells enriched for early progenitors by selective immunoadsorption and plated at low cell density (10(3) to 10(4) cells/mL/9.6 cm2) in semisolid methylcellulose culture, we have analyzed the cooperative effects of human colony-stimulating factor 1 (CSF-1), granulocyte-macrophage-CSF (GM-CSF), interleukin-1 alpha (IL-1 alpha), and gibbon as well as human recombinant IL-3 on the formation of monocytic colonies. CSF-1 alone stimulated mature monocytic colony formation by human CFU-M. However, in the presence of IL-3 and erythropoietin, CSF-1 stimulated maximal immature monocytic colony formation at low concentrations and inhibited the formation of granulomonocytic, erythrocytic, and mixed colonies. Cultures with CSF-1 and IL-3 contained more immature monocytic colonies than did cultures with CSF-1 alone. IL-1 alpha alone had little effect. However, IL-1 alpha in combination with optimal concentrations of either CSF-1, GM- CSF, or IL-3 increased the number of colonies containing immature or mature monocytic colonies.

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Interleukin-3 and interleukin-1 alpha allow earlier bone marrow progenitors to respond to human colony-stimulating factor 1

Blood ◽

10.1182/blood.v72.6.1870.bloodjournal7261870 ◽

1988 ◽

Vol 72 (6) ◽

pp. 1870-1874

Author(s):

YQ Zhou ◽

ER Stanley ◽

SC Clark ◽

JA Hatzfeld ◽

JP Levesque ◽

...

Keyword(s):

Bone Marrow ◽

Colony Formation ◽

Bone Marrow Cells ◽

Interleukin 1 ◽

Colony Stimulating Factor ◽

Cooperative Effects ◽

Gm Csf ◽

Low Concentrations ◽

Low Cell Density ◽

Stimulating Factor

By using human bone marrow cells enriched for early progenitors by selective immunoadsorption and plated at low cell density (10(3) to 10(4) cells/mL/9.6 cm2) in semisolid methylcellulose culture, we have analyzed the cooperative effects of human colony-stimulating factor 1 (CSF-1), granulocyte-macrophage-CSF (GM-CSF), interleukin-1 alpha (IL-1 alpha), and gibbon as well as human recombinant IL-3 on the formation of monocytic colonies. CSF-1 alone stimulated mature monocytic colony formation by human CFU-M. However, in the presence of IL-3 and erythropoietin, CSF-1 stimulated maximal immature monocytic colony formation at low concentrations and inhibited the formation of granulomonocytic, erythrocytic, and mixed colonies. Cultures with CSF-1 and IL-3 contained more immature monocytic colonies than did cultures with CSF-1 alone. IL-1 alpha alone had little effect. However, IL-1 alpha in combination with optimal concentrations of either CSF-1, GM- CSF, or IL-3 increased the number of colonies containing immature or mature monocytic colonies.

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Recombinant human macrophage colony-stimulating factor (M-CSF) requires subliminal concentrations of granulocyte/macrophage (GM)-CSF for optimal stimulation of human macrophage colony formation in vitro.

Journal of Experimental Medicine ◽

10.1084/jem.166.6.1851 ◽

1987 ◽

Vol 166 (6) ◽

pp. 1851-1860 ◽

Cited By ~ 46

Author(s):

D Caracciolo ◽

N Shirsat ◽

G G Wong ◽

B Lange ◽

S Clark ◽

...

Keyword(s):

Bone Marrow ◽

Colony Formation ◽

Human Macrophage ◽

Colony Stimulating Factor ◽

Colony Assay ◽

Gm Csf ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

Human macrophage colony-stimulating factor (M-CSF or CSF-1), either in purified or in recombinant form, is able to generate macrophagic colonies in a murine bone marrow colony assay, but only stimulates small macrophagic colonies of 40-50 cells in a human bone marrow colony assay. We report here that recombinant human granulocytic/macrophage colony stimulating factor (rhGM-CSF) at concentrations in the range of picograms enhances the responsiveness of bone marrow progenitors to M-CSF activity, resulting in an increased number of macrophagic colonies of up to 300 cells. Polyclonal antiserum against M-CSF did not alter colony formation of bone marrow progenitors incubated with GM-CSF at optimal concentration (1-10 ng/ml) for these in vitro assays. Thus, GM-CSF at higher concentrations (nanogram range) can by itself, elicit macrophagic colonies, and at lower concentrations (picogram range) acts to enhance the responsiveness of these progenitors to M-CSF.

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Effect of mouse interferon on growth and differentiation of mouse bone marrow cells stimulated by two different types of colony-stimulating factor

Blood ◽

10.1182/blood.v62.3.597.597 ◽

1983 ◽

Vol 62 (3) ◽

pp. 597-601 ◽

Cited By ~ 21

Author(s):

Y Yamamoto-Yamaguchi ◽

M Tomida ◽

M Hozumi

Keyword(s):

Bone Marrow ◽

Bone Marrow Cells ◽

Mouse Bone Marrow ◽

Colony Stimulating Factor ◽

Gm Csf ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor ◽

Mouse Bone Marrow Cells ◽

Marrow Cells

Abstract The effects of mouse L-cell interferon (IFN) on growth of mouse bone marrow cells and their differentiation into macrophages and granulocytes were investigated in a liquid suspension culture system with two different types of colony-stimulating factor (CSF). Within 7 days, most bone marrow cells differentiated into macrophages in the presence of macrophage colony-stimulating factor (M-CSF) derived from mouse fibroblast L929 cells, but into both granulocytes (40%) and macrophages (23%) in the presence of a granulocyte-macrophage colony- stimulating factor (GM-CSF) from mouse lung tissue. IFN inhibited growth of bone marrow cells with both M-CSF and GM-CSF, but had 20 times more effect on bone marrow cells stimulated with M-CSF than on those stimulated with GM-CSF. A low concentration of IFN (50 IU/ml) stimulated production of macrophages by GM-CSF in liquid culture medium, whereas it selectively inhibited colony formation of macrophages in semisolid agar culture. IFN caused no detectable block of late stages of differentiation; mature macrophages and granulocytes were produced even when cell proliferation was inhibited by IFN. These results indicate that IFN preferentially affects growth and differentiation of the cell lineage of macrophages among mouse bone marrow cells.

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Effect of mouse interferon on growth and differentiation of mouse bone marrow cells stimulated by two different types of colony-stimulating factor

Blood ◽

10.1182/blood.v62.3.597.bloodjournal623597 ◽

1983 ◽

Vol 62 (3) ◽

pp. 597-601 ◽

Cited By ~ 1

Author(s):

Y Yamamoto-Yamaguchi ◽

M Tomida ◽

M Hozumi

Keyword(s):

Bone Marrow ◽

Bone Marrow Cells ◽

Mouse Bone Marrow ◽

Colony Stimulating Factor ◽

Gm Csf ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor ◽

Mouse Bone Marrow Cells ◽

Marrow Cells

The effects of mouse L-cell interferon (IFN) on growth of mouse bone marrow cells and their differentiation into macrophages and granulocytes were investigated in a liquid suspension culture system with two different types of colony-stimulating factor (CSF). Within 7 days, most bone marrow cells differentiated into macrophages in the presence of macrophage colony-stimulating factor (M-CSF) derived from mouse fibroblast L929 cells, but into both granulocytes (40%) and macrophages (23%) in the presence of a granulocyte-macrophage colony- stimulating factor (GM-CSF) from mouse lung tissue. IFN inhibited growth of bone marrow cells with both M-CSF and GM-CSF, but had 20 times more effect on bone marrow cells stimulated with M-CSF than on those stimulated with GM-CSF. A low concentration of IFN (50 IU/ml) stimulated production of macrophages by GM-CSF in liquid culture medium, whereas it selectively inhibited colony formation of macrophages in semisolid agar culture. IFN caused no detectable block of late stages of differentiation; mature macrophages and granulocytes were produced even when cell proliferation was inhibited by IFN. These results indicate that IFN preferentially affects growth and differentiation of the cell lineage of macrophages among mouse bone marrow cells.

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Interleukin-1 synergizes with granulocyte-macrophage colony-stimulating factor on granulocytic colony formation by intermediate production of granulocyte colony-stimulating factor

Blood ◽

10.1182/blood.v74.7.2398.2398 ◽

1989 ◽

Vol 74 (7) ◽

pp. 2398-2404 ◽

Cited By ~ 13

Author(s):

MR Schaafsma ◽

JH Falkenburg ◽

N Duinkerken ◽

J Van Damme ◽

BW Altrock ◽

...

Keyword(s):

Bone Marrow Cells ◽

Interleukin 1 ◽

Colony Growth ◽

Colony Stimulating Factor ◽

Gm Csf ◽

Accessory Cells ◽

Granulocytic Colony ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

Abstract Interleukin-1 (IL-1) was found to act synergistically with granulocyte- macrophage colony-stimulating factor (GM-CSF) on granulocytic colony growth of normal human bone marrow cells, depleted of mononuclear phagocytes and T lymphocytes. Using CD34/HLA-DR-enriched bone marrow cells we demonstrated that this activity of IL-1 was not a direct action on hematopoietic progenitor cells, but an effect of an intermediate factor produced by residual accessory cells in response to IL-1. Neutralization experiments using an anti-IL-6 antiserum showed that IL-1-induced IL-6 did not contribute to the observed synergy. Furthermore, IL-6 by itself had neither a direct stimulatory effect on CFU-GM colony growth, nor did it act synergistically with GM-CSF on granulocytic or monocytic colony formation. Neutralization experiments with an anti-G-CSF monoclonal antibody showed that IL-1-induced G-CSF production was responsible for the synergy with GM-CSF. Using combinations of G-CSF and GM-CSF this synergistic activity could be detected at concentrations of G-CSF as low as 0.1 ng/mL (10 U/mL). Our results indicate that IL-1, but not IL-6, stimulates the GM-CSF- dependent proliferation of relatively mature myeloid progenitor cells in the presence of small numbers of accessory cells.

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In vivo administration of recombinant human interleukin-1 and macrophage colony-stimulating factor (M-CSF) induce a rapid loss of M- CSF receptors in mouse bone marrow cells and peritoneal macrophages: effect of administration route

Blood ◽

10.1182/blood.v77.9.1923.1923 ◽

1991 ◽

Vol 77 (9) ◽

pp. 1923-1928 ◽

Cited By ~ 7

Author(s):

BD Chen

Keyword(s):

Bone Marrow ◽

Bone Marrow Cells ◽

Interleukin 1 ◽

Colony Stimulating Factor ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

In Vivo Administration ◽

Stimulating Factor ◽

Marrow Cells

Abstract Earlier studies suggested the existence of a blood-bone marrow barrier that significantly inhibits the transfer of plasma macrophage colony- stimulating factor (M-CSF) to responsive hematopoietic cells in vivo as indicated by its failure to induce a receptor downregulation in bone marrow cells. In this study, the effect of recombinant human interleukin-1 (rhuIL-1) was investigated. In vivo administration of rhuIL-1, either intraperitoneally (IP) or intravenously (IV), induced a rapid transient loss of M-CSF receptor binding activity in bone marrow cells, with a nadir occurring between 2 to 4 hours while loss of M-CSF receptors by cells in the peritoneal cavity occurred only in animals receiving rhuIL-1 via IP administration. The loss of M-CSF receptor activity after rhuIL-1 treatment was correlated with an elevated level of circulating M-CSF. However, the loss of M-CSF receptors in marrow cells was prevented by dexamethasone (Dex) treatment before rhuIL-1 administration. The fact that Dex treatment also reduced the level of circulating M-CSF after rhuIL-1 administration suggests that the inhibitory effects of IL-1 are mediated through locally produced M-CSF. Administration of rhuM-CSF at higher doses, either IV or IP, also induced a loss of M-CSF receptor of lesser degree in the marrow cells. However, the loss of M-CSF receptors by the peritoneal cells was induced only in mice receiving rhuM-CSF through IP administration. Taken together, these results indicate the existence of a unidirectional barrier that prevents the transfer of blood M-CSF and IL- 1 to peritoneal cavity but not vice versa.

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Macrophage colony-stimulating factor-induced bone marrow macrophages do not synthesize or release prostaglandin E2

Blood ◽

10.1182/blood.v83.11.3316.3316 ◽

1994 ◽

Vol 83 (11) ◽

pp. 3316-3323 ◽

Cited By ~ 8

Author(s):

Y Shibata ◽

DR Bjorkman ◽

M Schmidt ◽

Y Oghiso ◽

A Volkman

Keyword(s):

Bone Marrow ◽

Enzyme Activity ◽

Prostaglandin E2 ◽

Bone Marrow Cells ◽

Mrna Levels ◽

Colony Stimulating Factor ◽

Murine Bone Marrow ◽

Gm Csf ◽

Stimulating Factor

Abstract Previously, we found that murine bone marrow-derived macrophages (MO) induced in vitro by MO-specific colony-stimulating factor (M-CSF) have little capacity to release prostaglandin E2 (PGE2) and other eicosanoids. This work focused on the functional and transcriptional expression of the key enzymes for the PGE2 synthesis in the MO. Nonadherent bone marrow cells were cultured with RPMI1640 plus 10% fetal bovine serum (FBS) further supplemented with either M-CSF or granulocyte-macrophage (GM)-CSF and interleukin-3 (IL-3). Cellular PGG/H synthase (cyclooxygenase) levels were quantified by cytometric analysis with antibodies specific for the two isozymes of PGG/H synthase (PGG/H synthases 1 and 2). The enzyme activity was monitored by adding exogenous arachidonic acid (AA) substrate to the bone marrow MO cultures and to the cell-free particulate fractions. The levels of PGE2 converted were quantitated by radioimmunoassay (RIA). mRNA levels of the enzymes were detected by Northern blot analysis hybridized with mouse PGG/H synthase cDNA probes, 2.7 kb (PGG/H synthase 1) and 4.2 kb (PGG/H synthase 2). In addition, cellular phospholipase A2 (PLA2) activities were detected with sn-2–14C-arachidonyl phosphatidylcholine as a substrate. Cells proliferating in the presence of GM-CSF and IL-3 for more than 4 days showed significant release of PGE2 (> 7 ng/10(6) cells) when stimulated by AA. These cells also expressed significant amounts of PGG/H synthase 1 protein, its mRNA (2.7 kb) and cellular PLA2. M-CSF-induced MO, in sharp contrast, expressed little PGG/H synthase protein, mRNA, cellular enzyme activity, or PGE2 release, despite comparable levels of cellular PLA2 activity. These data suggest that the capacity of differentiating marrow-derived MO to form PGE2 is growth factor-dependent.

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In vivo administration of recombinant human interleukin-1 and macrophage colony-stimulating factor (M-CSF) induce a rapid loss of M- CSF receptors in mouse bone marrow cells and peritoneal macrophages: effect of administration route

Blood ◽

10.1182/blood.v77.9.1923.bloodjournal7791923 ◽

1991 ◽

Vol 77 (9) ◽

pp. 1923-1928

Author(s):

BD Chen

Keyword(s):

Bone Marrow ◽

Bone Marrow Cells ◽

Interleukin 1 ◽

Colony Stimulating Factor ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

In Vivo Administration ◽

Stimulating Factor ◽

Marrow Cells

Earlier studies suggested the existence of a blood-bone marrow barrier that significantly inhibits the transfer of plasma macrophage colony- stimulating factor (M-CSF) to responsive hematopoietic cells in vivo as indicated by its failure to induce a receptor downregulation in bone marrow cells. In this study, the effect of recombinant human interleukin-1 (rhuIL-1) was investigated. In vivo administration of rhuIL-1, either intraperitoneally (IP) or intravenously (IV), induced a rapid transient loss of M-CSF receptor binding activity in bone marrow cells, with a nadir occurring between 2 to 4 hours while loss of M-CSF receptors by cells in the peritoneal cavity occurred only in animals receiving rhuIL-1 via IP administration. The loss of M-CSF receptor activity after rhuIL-1 treatment was correlated with an elevated level of circulating M-CSF. However, the loss of M-CSF receptors in marrow cells was prevented by dexamethasone (Dex) treatment before rhuIL-1 administration. The fact that Dex treatment also reduced the level of circulating M-CSF after rhuIL-1 administration suggests that the inhibitory effects of IL-1 are mediated through locally produced M-CSF. Administration of rhuM-CSF at higher doses, either IV or IP, also induced a loss of M-CSF receptor of lesser degree in the marrow cells. However, the loss of M-CSF receptors by the peritoneal cells was induced only in mice receiving rhuM-CSF through IP administration. Taken together, these results indicate the existence of a unidirectional barrier that prevents the transfer of blood M-CSF and IL- 1 to peritoneal cavity but not vice versa.

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Stimulation of human myelopoiesis by leukotrienes B4 and C4: interactions with granulocyte-macrophage colony-stimulating factor

Blood ◽

10.1182/blood.v81.2.352.bloodjournal812352 ◽

1993 ◽

Vol 81 (2) ◽

pp. 352-356

Author(s):

L Stenke ◽

M Mansour ◽

P Reizenstein ◽

JA Lindgren

Keyword(s):

Colony Formation ◽

Bone Marrow Cells ◽

Growth Stimulation ◽

Colony Stimulating Factor ◽

Gm Csf ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Synthase Inhibitor ◽

Stimulating Factor ◽

Stimulation Of

The regulatory role of leukotrienes (LT) on human myelopoiesis was investigated. Mononuclear bone marrow cells from 31 healthy donors were cultivated in the presence of suboptimal concentrations of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) for 10 days in semisolid agar. The addition of LTC4 or LTB4 to the cultures dose- dependently stimulated myeloid stem cell proliferation. Maximal effects were observed at 10(-8) mol/L, at which LTC4 induced a 91% +/- 23% (mean +/- SEM; P = .004) and LTB4 a 73% +/- 22% (P = .008) increase in colony formation. In contrast, addition of the LTB4 isomer 5(S), 12(S)- diHETE did not affect the growth. LTD4 exerted a weak potentiating effect on progenitor proliferation (17% +/- 7% growth stimulation at 10(-10) mol/L; P = .034), whereas LTE4 was without consistent effect. Furthermore, LTC4-induced stimulation of colony formation was insensitive to the LTD4 antagonist ICI 198615. The dual lipoxygenase and prostaglandin endoperoxide synthase inhibitor CL42A potently suppressed the proliferation of myeloid colonies, a suppression that could be reversed by parallel addition of LTB4 or LTC4. The results suggest that both LTB4 and LTC4 possess strong and specific synergistic stimulatory effects on GM-CSF-induced human myeloid progenitor cell growth.

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Biosynthetic (recombinant) human granulocyte-macrophage colony- stimulating factor: effect on normal bone marrow and leukemia cell lines

Blood ◽

10.1182/blood.v67.1.31.31 ◽

1986 ◽

Vol 67 (1) ◽

pp. 31-36 ◽

Cited By ~ 113

Author(s):

M Tomonaga ◽

DW Golde ◽

JC Gasson

Keyword(s):

Bone Marrow ◽

Progenitor Cells ◽

Bone Marrow Cells ◽

Leukemia Cell ◽

Colony Stimulating Factor ◽

Normal Peripheral Blood ◽

Gm Csf ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

Abstract To examine the biologic properties of the molecule encoded by the human gene for granulocyte-macrophage colony-stimulating factor (GM-CSF), we expressed the cloned complementary DNA (cDNA) in transfected monkey COS cells and purified the resultant protein. Purified biosynthetic human GM-CSF was added to cultures of normal hematopoietic progenitor cells in semisolid media, and the resulting colonies were characterized cytochemically. Non-adherent light-density bone marrow cells from healthy adult volunteers were maximally stimulated with GM-CSF (approximately 250 pmol/L, and four types of colonies were consistently identified by aspirating the individual colonies and staining with a triple stain for specific and nonspecific esterases and eosinophilic granules. Pure neutrophilic granulocyte (G), mixed granulocyte- macrophage (GM), pure macrophage (M), and pure eosinophil (EO) colonies were observed, the mean incidences on day 8 being 70%, 20%, 5%, and 5%, and on day 14, 7.5%, 16.6%, 50.9%, and 25.0%, respectively. In all types of colonies, complete maturation to segmented forms or typical macrophages was detected. GM-CSF did not enhance the growth of BFU-E from normal peripheral blood buffy coat cells in the simultaneous presence of erythropoietin alone or erythropoietin with purified erythroid-potentiating activity. GM-CSF stimulated HL-60 and KG-1 colony formation twofold and fivefold, respectively; consistent differentiation induction towards monocytic and eosinophilic lineages was observed in HL-60 but not in KG-1. These in vitro findings indicate that GM-CSF is a multilineage stimulator for progenitor cells of G, GM, M, and EO colonies.

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