scholarly journals Monocyte-macrophage-derived acidic isoferritins: normal feedback regulators of granulocyte-macrophage progenitor cells in vitro

Blood ◽  
1982 ◽  
Vol 60 (3) ◽  
pp. 595-607 ◽  
Author(s):  
HE Broxmeyer ◽  
J Bognacki ◽  
P Ralph ◽  
MH Dorner ◽  
L Lu ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Inhibitory Activity ◽  
Mononuclear Phagocytes ◽  
Pokeweed Mitogen ◽  
Target Cells ◽  
Continuous Cell Lines ◽  
Gm Csf ◽  
Monocytes And Macrophages ◽  
Macrophage Colony

Abstract The recent identification of a leukemia-associated inhibitory activity (LIA) against granulocyte-macrophage progenitor cells (CFU-GM) as acidic isoferritins has now led to detection of this activity in normal bone marrow and blood cells. Detection of this activity depends on stimulation of CFU-GM by granulocyte-macrophage colony stimulatory factors (GM-CSF), and some conditioned media (CM) sources of GM-CSF (human placental and monocyte, mouse macrophage and WEHI-3) contained low levels of acidic isoferritin that lowered colony formation. Inactivation or removal of this activity increased the stimulatory capacity of the CM. CM depleted of acidic isoferritins or CM originally devoid of this activity (human GCT, 5637, Mo, lymphocytes: mouse L cells or pokeweed-mitogen-stimulated spleen cells) increased the sensitivity of the assay to detect acidic isoferritin inhibitory activity. This activity was selectively contained and released from normal monocytes and macrophages. Restriction of this activity to mononuclear phagocytes was substantiated, as only continuous cell lines of monocytes and macrophages or lines capable of induction to this lineage contained and released acidic isoferritin inhibitory activity. The cells of origin and target cells of action suggest that acidic isoferritin-inhibitory activity can be considered as a negative feedback regulator, at least in vitro.

scholarly journals Monocyte-macrophage-derived acidic isoferritins: normal feedback regulators of granulocyte-macrophage progenitor cells in vitro

Blood ◽  
1982 ◽  
Vol 60 (3) ◽  
pp. 595-607
Author(s):  
HE Broxmeyer ◽  
J Bognacki ◽  
P Ralph ◽  
MH Dorner ◽  
L Lu ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Inhibitory Activity ◽  
Mononuclear Phagocytes ◽  
Pokeweed Mitogen ◽  
Target Cells ◽  
Continuous Cell Lines ◽  
Gm Csf ◽  
Monocytes And Macrophages ◽  
Macrophage Colony

The recent identification of a leukemia-associated inhibitory activity (LIA) against granulocyte-macrophage progenitor cells (CFU-GM) as acidic isoferritins has now led to detection of this activity in normal bone marrow and blood cells. Detection of this activity depends on stimulation of CFU-GM by granulocyte-macrophage colony stimulatory factors (GM-CSF), and some conditioned media (CM) sources of GM-CSF (human placental and monocyte, mouse macrophage and WEHI-3) contained low levels of acidic isoferritin that lowered colony formation. Inactivation or removal of this activity increased the stimulatory capacity of the CM. CM depleted of acidic isoferritins or CM originally devoid of this activity (human GCT, 5637, Mo, lymphocytes: mouse L cells or pokeweed-mitogen-stimulated spleen cells) increased the sensitivity of the assay to detect acidic isoferritin inhibitory activity. This activity was selectively contained and released from normal monocytes and macrophages. Restriction of this activity to mononuclear phagocytes was substantiated, as only continuous cell lines of monocytes and macrophages or lines capable of induction to this lineage contained and released acidic isoferritin inhibitory activity. The cells of origin and target cells of action suggest that acidic isoferritin-inhibitory activity can be considered as a negative feedback regulator, at least in vitro.

scholarly journals The nature and action of granulocyte-macrophage colony stimulating factors

Blood ◽  
1980 ◽  
Vol 56 (6) ◽  
pp. 947-958 ◽  
Author(s):  
AW Burgess ◽  
D Metcalf
Keyword(s):  
Progenitor Cells ◽  
Leukemic Cells ◽  
Mouse Lung ◽  
Target Cells ◽  
In Vitro Production ◽  
In Vitro Proliferation ◽  
Gm Csf ◽  
Macrophage Colony

Granulocyte-macrophage colony stimulating factor (GM-CSF) stimulates the in vitro proliferation and differentiation of granulocytic and macrophage cells. This regulator is now known to act at other levels of hemopoietic regulation. The heterogeneity of GM-CSFs is not only related to the tissue of origin and the in vitro production method, but also to functional subclasses of the molecule that have distinct biologic specificities. Most adult mouse organs produce GM-CSF (mol wt 23,000), but a macrophage (M)-CSF has been detected in fetal conditioned medium (CM) and isolated from L-cell CM. Murine endotoxin serum appears to contain a M-CSF, GM-CSF, and G-CSF, the last of which cofractionates with a differentiation factor active on leukemic cells. Human GM-CSFs, G-CSF, and EO-CSFs active on human cells have been detected in a variety of CM, but as yet none have been purified. Again, there are subclasses of progenitor cells that respond to particular forms of human active CSFs. GM-CSF isolated from mouse lung CM stimulates multipotential progenitor cells, the initial proliferatin of progenitors in the erythroid, eosinophil, and megakaryocyte series, as well as mature cells in the GM series. While GM-CSF is also able to stimulate the differentiation of myeloid leukemic cells, other factors appear to be more potent in this respect. Information on the regulation of GM-CSF production, on the modulators of its action on specific target cells, and on its role in vivo will be required before the physiologic function of this molecule can be properly assessed.

scholarly journals Activities of four purified growth factors on highly enriched human hematopoietic progenitor cells

Blood ◽  
1987 ◽  
Vol 69 (5) ◽  
pp. 1508-1523 ◽  
Author(s):  
A Strife ◽  
C Lambek ◽  
D Wisniewski ◽  
S Gulati ◽  
JC Gasson ◽  
...  
Keyword(s):  
Growth Factors ◽  
Progenitor Cells ◽  
Human Growth ◽  
Positive Control ◽  
Velocity Sedimentation ◽  
Target Cells ◽  
Detectable Activity ◽  
Gm Csf ◽  
Macrophage Colony

Abstract The activities of four purified human growth factors: biosynthetic (recombinant) granulocyte-macrophage colony-stimulating factor (GM- CSF); recombinant erythroid-potentiating activity (EPA); natural and recombinant pluripoietin (Ppo); and natural pluripoietin alpha (Ppo alpha), were compared on the growth of hematopoietic colonies from enriched populations of human marrow and blood progenitor cells. Conditioned medium from the Mo T cell line (MoCM) was used as a standard positive control. We found that activities of GM-CSF and Ppo alpha on the growth of hematopoietic colonies were indistinguishable; Ppo alpha is now believed to be identical to GM-CSF. Both factors were able to promote the growth of colonies derived from subpopulations of CFU-GM, BFU-E, and CFU-GEM. Colonies derived from CFU-GM and CFU-GEM in cultures stimulated by GM-CSF and Ppo alpha were much smaller than in cultures stimulated by MoCM. In contrast to previous reports in which less highly enriched progenitors were used as target cells, Ppo had no detectable activity on the growth of colonies derived from BFU-E or CFU- GEM but promoted the growth of a subpopulation of CFU-GM derived colonies. Ppo is now recognized to be identical to G-CSF. The GM colonies in cultures stimulated by G-CSF (Ppo) were much smaller than in cultures stimulated by MoCM. EPA had no detectable activity on either the size or number of colonies derived from CFU-GM, BFU-E, or CFU-GEM. Results from experiments using target cell populations of marrow fractions separated by velocity sedimentation and marrow populations following freezing suggested that GM-CSF (Ppo alpha) and G- CSF (Ppo) primarily affect the growth of relatively mature subpopulations of progenitor cells. It is clear from these results that additional factor(s) are present in MoCM that are necessary to stimulate CFU-GM, BFU-E, and CFU-GEM maximally in vitro.

scholarly journals The nature and action of granulocyte-macrophage colony stimulating factors

Blood ◽  
1980 ◽  
Vol 56 (6) ◽  
pp. 947-958 ◽  
Author(s):  
AW Burgess ◽  
D Metcalf
Keyword(s):  
Progenitor Cells ◽  
Leukemic Cells ◽  
Mouse Lung ◽  
Target Cells ◽  
In Vitro Production ◽  
In Vitro Proliferation ◽  
Gm Csf ◽  
Macrophage Colony

Abstract Granulocyte-macrophage colony stimulating factor (GM-CSF) stimulates the in vitro proliferation and differentiation of granulocytic and macrophage cells. This regulator is now known to act at other levels of hemopoietic regulation. The heterogeneity of GM-CSFs is not only related to the tissue of origin and the in vitro production method, but also to functional subclasses of the molecule that have distinct biologic specificities. Most adult mouse organs produce GM-CSF (mol wt 23,000), but a macrophage (M)-CSF has been detected in fetal conditioned medium (CM) and isolated from L-cell CM. Murine endotoxin serum appears to contain a M-CSF, GM-CSF, and G-CSF, the last of which cofractionates with a differentiation factor active on leukemic cells. Human GM-CSFs, G-CSF, and EO-CSFs active on human cells have been detected in a variety of CM, but as yet none have been purified. Again, there are subclasses of progenitor cells that respond to particular forms of human active CSFs. GM-CSF isolated from mouse lung CM stimulates multipotential progenitor cells, the initial proliferatin of progenitors in the erythroid, eosinophil, and megakaryocyte series, as well as mature cells in the GM series. While GM-CSF is also able to stimulate the differentiation of myeloid leukemic cells, other factors appear to be more potent in this respect. Information on the regulation of GM-CSF production, on the modulators of its action on specific target cells, and on its role in vivo will be required before the physiologic function of this molecule can be properly assessed.

scholarly journals Activities of four purified growth factors on highly enriched human hematopoietic progenitor cells

Blood ◽  
1987 ◽  
Vol 69 (5) ◽  
pp. 1508-1523 ◽  
Author(s):  
A Strife ◽  
C Lambek ◽  
D Wisniewski ◽  
S Gulati ◽  
JC Gasson ◽  
...  
Keyword(s):  
Growth Factors ◽  
Progenitor Cells ◽  
Human Growth ◽  
Positive Control ◽  
Velocity Sedimentation ◽  
Target Cells ◽  
Detectable Activity ◽  
Gm Csf ◽  
Macrophage Colony

The activities of four purified human growth factors: biosynthetic (recombinant) granulocyte-macrophage colony-stimulating factor (GM- CSF); recombinant erythroid-potentiating activity (EPA); natural and recombinant pluripoietin (Ppo); and natural pluripoietin alpha (Ppo alpha), were compared on the growth of hematopoietic colonies from enriched populations of human marrow and blood progenitor cells. Conditioned medium from the Mo T cell line (MoCM) was used as a standard positive control. We found that activities of GM-CSF and Ppo alpha on the growth of hematopoietic colonies were indistinguishable; Ppo alpha is now believed to be identical to GM-CSF. Both factors were able to promote the growth of colonies derived from subpopulations of CFU-GM, BFU-E, and CFU-GEM. Colonies derived from CFU-GM and CFU-GEM in cultures stimulated by GM-CSF and Ppo alpha were much smaller than in cultures stimulated by MoCM. In contrast to previous reports in which less highly enriched progenitors were used as target cells, Ppo had no detectable activity on the growth of colonies derived from BFU-E or CFU- GEM but promoted the growth of a subpopulation of CFU-GM derived colonies. Ppo is now recognized to be identical to G-CSF. The GM colonies in cultures stimulated by G-CSF (Ppo) were much smaller than in cultures stimulated by MoCM. EPA had no detectable activity on either the size or number of colonies derived from CFU-GM, BFU-E, or CFU-GEM. Results from experiments using target cell populations of marrow fractions separated by velocity sedimentation and marrow populations following freezing suggested that GM-CSF (Ppo alpha) and G- CSF (Ppo) primarily affect the growth of relatively mature subpopulations of progenitor cells. It is clear from these results that additional factor(s) are present in MoCM that are necessary to stimulate CFU-GM, BFU-E, and CFU-GEM maximally in vitro.

scholarly journals Interleukin-6 synergizes with M-CSF in the formation of macrophage colonies from purified human marrow progenitor cells

Blood ◽  
1989 ◽  
Vol 73 (2) ◽  
pp. 435-437 ◽  
Author(s):  
FJ Bot ◽  
L van Eijk ◽  
L Broeders ◽  
LA Aarden ◽  
B Lowenberg
Keyword(s):  
Progenitor Cells ◽  
Interleukin 6 ◽  
Colony Formation ◽  
Interferon Beta ◽  
B Lymphocyte ◽  
Gm Csf ◽  
Human Immune ◽  
Macrophage Colony ◽  
Dose Dependent

Abstract We examined the in vitro stimulative effects of recombinant human interleukin-6 (IL-6, or interferon-beta 2) on purified human bone marrow progenitor cells. IL-6 alone or in combination with erythropoietin (Epo), IL-3, GM-CSF, or G-CSF did not induce colony formation. However, IL-6 strongly synergized with M-CSF in stimulating macrophage colony formation (colony numbers and size). The magnitude of IL-6 synergism with M-CSF was dose dependent; maximal potentiation of M- colony formation was evident at approximately 100 to 1,000 U/mL IL-6. When the addition of IL-6 to M-CSF-supplemented cultures was delayed for more than one day after the beginning of culture, enhancement of macrophage colony formation was lost. IL-6 stimulation of M-CSF- responsive colony formation was not apparent when nonpurified marrow cells were plated, most likely due to endogenous IL-6 release. These observations suggest that IL-6, in addition to playing a role in B- lymphocyte proliferation can potentiate the human immune defence mechanism by stimulating monocyte-macrophage development as well.

scholarly journals Interleukin-1 alpha enhances the in vitro survival of purified murine granulocyte-macrophage progenitor cells in the absence of colony- stimulating factors

Blood ◽  
1988 ◽  
Vol 72 (5) ◽  
pp. 1608-1615 ◽  
Author(s):  
DE Williams ◽  
HE Broxmeyer
Keyword(s):  
Progenitor Cells ◽  
Direct Action ◽  
Interleukin 1 ◽  
Hematopoietic Stem ◽  
Colony Stimulating Factors ◽  
Gm Csf ◽  
Accessory Cells ◽  
Alpha Effect ◽  
Macrophage Colony

Abstract Interleukin-1 (IL-1), recently identified as hemopoietin-1, affects hematopoiesis by presumably direct and indirect mechanisms. IL-1 stimulates primitive hematopoietic stem cells to express receptors for the granulocyte-macrophage colony-stimulating factors (GM-CSFs) and stimulates CSF release from accessory cells. We used highly purified murine granulocyte-macrophage progenitor cells (CFU-GM, up to 92% cloning efficiency) to assess the effects of IL-1 alpha on the proliferation, differentiation, and survival of these cells. The results demonstrated that IL-1 alpha does not directly influence the proliferation or differentiation of purified CFU-GM in the presence of plateau concentrations of purified natural or recombinant CSFs, and IL- 1 alpha lacks intrinsic CSF activity of its own. CSF deprivation studies showed that IL-1 alpha rapidly (within one hour) promoted CFU- GM survival in the absence of CSF. This enhanced survival stimulated by IL-1 alpha was observed with CFU-GM responding to purified recombinant GM-CSF, natural M-CSF, recombinant G-CSF, recombinant IL-3, or IL-3 in WEHI-conditioned medium, and no effect on the pattern of CFU-GM differentiation occurred in cultures incubated with IL-1 alpha in the absence of CSF. The IL-1 alpha effects on CFU-GM are probably due to a direct action on progenitor cells because the presence or absence of accessory cells did not alter the results and concentrations of the CSFs that were too low to stimulate the proliferation of CFU-GM could not mimic the IL-1 alpha effect on CFU-GM survival.

scholarly journals Granulomonocyte-associated lysosomal protein expression during in vitro expansion and differentiation of CD34+ hematopoietic progenitor cells

Blood ◽  
1995 ◽  
Vol 86 (11) ◽  
pp. 4115-4123 ◽  
Author(s):  
C Scheinecker ◽  
H Strobl ◽  
G Fritsch ◽  
B Csmarits ◽  
O Krieger ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Cell Number ◽  
Gm Csf ◽  
Human Cd34 ◽  
Cd34 Cells ◽  
In Vitro Expansion ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Kinetics Of

Using an in vitro expansion and differentiation system for human CD34+ cord blood (CB) progenitor cells, we analyzed the induction and expression kinetics of the granulomonocyte associated lysosomal proteins myeloperoxidase (MPO), lysozyme (LZ), lactoferrin (LF), and macrosialin (CD68). Freshly isolated CD34+ CB cells were negative for LZ and LF, and only small proportions expressed MPO (4% +/- 2%) or CD68 (3% +/- 1%). Culturing of CD34+ cells for 14 days with interleukin (IL)- 1, IL-3, IL-6, stem cell factor, granulocyte-macrophage colony- stimulating factor (GM-CSF), and G-CSF resulted in on average a 1,750- fold amplification of cell number, of which 83% +/- 7% were MPO+. Without addition of GM-CSF and G-CSF, lower increases in total cell numbers (mean, 211-fold) and lower proportions of MPO+ cells (54% +/- 11%) were observed. The proportion of MPO+ cells slightly exceeded but clearly correlated with the proportion of cells positive for the granulomonocyte associated surface molecules CD11b (Mac-1), CD15 (LeX), CD64 (Fc gamma RI) CD66, or CD89 (Fc alpha R). At day 14 MPO+ and LZ+ cells were virtually identical. However, at earlier time points during culture (days 4 and 7), single MPO+ or LZ+ cell populations were also observed, which only later acquired LZ and MPO, respectively. Maturation of cells into the neutrophilic pathway was indicated by the acquisition of MPO, followed by LZ. In contrast, maturation of cells into the monocytic pathway was indicated by the acquisition of LZ followed by MPO and CD14. CD68 was found to be expressed at day 4 by the majority of cells and was not restricted to the granulomonocytic cells, as cells with megakariocytic (CD41+) or erythroid (CD71hi) features were CD68+. LF expression was observed only in GM- plus G-CSF- supplemented cultures, in which only 26% +/- 5% of cells expressed LF by day 14.

scholarly journals Hematopoietic precursors in disease induced by the myeloproliferative sarcoma virus

Blood ◽  
1983 ◽  
Vol 62 (2) ◽  
pp. 305-307 ◽  
Author(s):  
B Klein ◽  
JJ Akouala ◽  
C Le Bousse-Kerdiles ◽  
F Smadja-Joffe ◽  
C Jasmin
Keyword(s):  
Pokeweed Mitogen ◽  
Spleen Cells ◽  
In Vitro Proliferation ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Proliferation And Differentiation ◽  
Sarcoma Virus ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony

Abstract Granulocyte and macrophage precursors (GM-CFU-C-), which differentiate in vitro without added granulocyte and macrophage colony stimulating factor (GM-CSF), can be detected in the hematopoietic organs of mice infected with myeloproliferative sarcoma virus (MPSV). Retransplantation experiments have shown that the GM-CFU-C- are incapable of autonomous growth and depend on a factor present in medium conditioned by MPSV spleen cells (MPSV-CM). This factor is not MPSV and is not produced by spleen cells of noninfected mice. Two classical sources of GM-CSF, lung GM-CSF and GM-CSF contained in the plasma of endotoxin-treated mice, cannot replace the MPSV factor. Inversely, MPSV- CM does not stimulate the growth of retransplanted clusters induced in normal bone marrow with lung GM-CSF, whereas lung GM-CSF does. Two conditioned media containing activity promoting the in vitro proliferation and differentiation of hematopoietic stem cells in the mixed colony assay stimulate the growth of MPSV clusters: one medium was conditioned by pokeweed-mitogen-stimulated spleen cells, the other by the WEHI 3 cell line. The implication of the results in the comprehension of MPSV disease is discussed.

Proliferation in Monocyte-Derived Dendritic Cell Cultures Is Caused by Progenitor Cells Capable of Myeloid Differentiation

Blood ◽  
1998 ◽  
Vol 92 (5) ◽  
pp. 1598-1607 ◽  
Author(s):  
Lois L. Cavanagh ◽  
Russell J. Saal ◽  
Karen L. Grimmett ◽  
Ranjeny Thomas
Keyword(s):  
T Cells ◽  
Progenitor Cells ◽  
Clinical Importance ◽  
Interleukin 4 ◽  
Gm Csf ◽  
Myeloid Progenitor Cells ◽  
Macrophage Colony ◽  
American Society ◽  
Antigen Presenting

Abstract Dendritic cells (DC) can be generated by culture of adherent peripheral blood (PB) cells in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). There is controversy as to whether these DC arise from proliferating precursors or simply from differentiation of monocytes. DC were generated from myeloid-enriched PB non-T cells or sorted monocytes. DC generated from either population functioned as potent antigen-presenting cells. Uptake of [3H]-thymidine was observed in DC cultured from myeloid-enriched non-T cells. Addition of lipopolysaccharide or tumor necrosis factor- led to maturation of the DC, but did not inhibit proliferation. Ki67+ cells were observed in cytospins of these DC, and by double staining were CD3−CD19−CD11c−CD40−and myeloperoxidase+, suggesting that they were myeloid progenitor cells. Analysis of the starting population by flow cytometry demonstrated small numbers of CD34+CD33−CD14− progenitor cells, and numerous granulocyte-macrophage colony-forming units were generated in standard assays. Thus, production of DC in vitro from adherent PB cells also enriches for progenitor cells that are capable of proliferation after exposure to GM-CSF. Of clinical importance, the yield of DC derived in the presence of GM-CSF and IL-4 cannot be expanded beyond the number of starting monocytes. © 1998 by The American Society of Hematology.

Sign in / Sign up

Export Citation Format

Share Document