scholarly journals Mast cell growth factor (c-kit ligand) supports the growth of human multipotential progenitor cells with a high replating potential

Blood ◽  
1991 ◽  
Vol 78 (9) ◽  
pp. 2216-2221 ◽  
Author(s):  
CE Carow ◽  
G Hangoc ◽  
SH Cooper ◽  
DE Williams ◽  
HE Broxmeyer
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Growth Factor ◽  
Cell Growth ◽  
Cord Blood ◽  
Primary Cultures ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Factor C ◽  
Mast Cell Growth Factor

Abstract The replating capability of human multipotential (colony-forming unit- granulocyte-erythrocyte-macrophage-megakaryocyte [CFU-GEMM]) and erythroid (burst-forming unit-erythroid [BFU-E]) progenitors was assessed in vitro as a potential measure of self-renewal using purified, recombinant (r) human (hu) or murine (mu) mast cell growth factor (MGF), a ligand for the c-kit proto-oncogene receptor. Primary cultures of human umbilical cord blood or adult human bone marrow cells were initiated in methylcellulose with erythropoietin (Epo) alone or in combination with rhu interleukin-3 (IL-3) or MGF. Individual day 14 to 18 CFU-GEMM or BFU-E colonies were removed from primary cultures and reseeded into secondary methylcellulose cultures containing a combination of Epo, MGF, and rhu granulocyte-macrophage colony- stimulating factor (GM-CSF). The data showed a high replating efficiency of cord blood and bone marrow CFU-GEMM in response to Epo + MGF in terms of the percentage of colonies that could be replated and the number of secondary colonies formed per replated primary colony. The average number of hematopoietic colonies and clusters apparent from replated cultures of cord blood or bone marrow CFU-GEMM stimulated by Epo + MGF was greater than with Epo + rhuIL-3 or Epo alone. Replated cord blood CFU-GEMM gave rise to CFU-GEMM, BFU-E, and GM colony-forming units (CFU-GM) in secondary cultures. Replated bone marrow CFU-GEMM gave rise mainly to CFU-GM in secondary cultures. A more limited capacity for replating of cord blood and bone marrow BFU-E was observed. These studies show that CFU-GEMM responding to MGF have an enhanced replating potential, which may be promoted by MGF. These studies also support the concept that MGF acts on more primitive progenitors than IL-3.

scholarly journals Mast cell growth factor (c-kit ligand) supports the growth of human multipotential progenitor cells with a high replating potential

Blood ◽  
1991 ◽  
Vol 78 (9) ◽  
pp. 2216-2221
Author(s):  
CE Carow ◽  
G Hangoc ◽  
SH Cooper ◽  
DE Williams ◽  
HE Broxmeyer
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Growth Factor ◽  
Cell Growth ◽  
Cord Blood ◽  
Primary Cultures ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Factor C ◽  
Mast Cell Growth Factor

The replating capability of human multipotential (colony-forming unit- granulocyte-erythrocyte-macrophage-megakaryocyte [CFU-GEMM]) and erythroid (burst-forming unit-erythroid [BFU-E]) progenitors was assessed in vitro as a potential measure of self-renewal using purified, recombinant (r) human (hu) or murine (mu) mast cell growth factor (MGF), a ligand for the c-kit proto-oncogene receptor. Primary cultures of human umbilical cord blood or adult human bone marrow cells were initiated in methylcellulose with erythropoietin (Epo) alone or in combination with rhu interleukin-3 (IL-3) or MGF. Individual day 14 to 18 CFU-GEMM or BFU-E colonies were removed from primary cultures and reseeded into secondary methylcellulose cultures containing a combination of Epo, MGF, and rhu granulocyte-macrophage colony- stimulating factor (GM-CSF). The data showed a high replating efficiency of cord blood and bone marrow CFU-GEMM in response to Epo + MGF in terms of the percentage of colonies that could be replated and the number of secondary colonies formed per replated primary colony. The average number of hematopoietic colonies and clusters apparent from replated cultures of cord blood or bone marrow CFU-GEMM stimulated by Epo + MGF was greater than with Epo + rhuIL-3 or Epo alone. Replated cord blood CFU-GEMM gave rise to CFU-GEMM, BFU-E, and GM colony-forming units (CFU-GM) in secondary cultures. Replated bone marrow CFU-GEMM gave rise mainly to CFU-GM in secondary cultures. A more limited capacity for replating of cord blood and bone marrow BFU-E was observed. These studies show that CFU-GEMM responding to MGF have an enhanced replating potential, which may be promoted by MGF. These studies also support the concept that MGF acts on more primitive progenitors than IL-3.

scholarly journals Effect of murine mast cell growth factor (c-kit proto-oncogene ligand) on colony formation by human marrow hematopoietic progenitor cells

Blood ◽  
1991 ◽  
Vol 77 (10) ◽  
pp. 2142-2149 ◽  
Author(s):  
HE Broxmeyer ◽  
S Cooper ◽  
L Lu ◽  
G Hangoc ◽  
D Anderson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Growth Factor ◽  
Cell Growth ◽  
Progenitor Cells ◽  
Colony Formation ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Hla Dr ◽  
Mast Cell Growth Factor

Purified natural (n) and recombinant (r) murine (mu) mast cell growth factor (MGF, a c-kit ligand) were evaluated alone and in combination with r human (hu) erythropoietin (Epo), rhu granulocyte-macrophage colony-stimulating factor (rhuGM-CSF), rhuG-CSF, and/or rhuM-CSF for effects in vitro on colony formation by multipotential (colony-forming unit-granulocyte, erythroid, monocyte, megakaryocyte [CFU-GEMM]), erythroid (burst-forming unit erythroid [BFU-E]) and granulocyte- macrophage (CFU-GM) progenitor cells from normal human bone marrow. MGF was a potent enhancing cytokine for Epo-dependent CFU-GEMM and BFU-E colony formation, stimulating more colonies and of a larger size than either rhu interleukin-3 (rhuIL-3) or rhuGM-CSF. MGF, especially at lower concentrations, also acted with rhuIL-3 or rhuGM-CSF to enhance Epo-dependent CFU-GEMM and BFU-E colony formation. MGF had little stimulating activity for CFU-GM colonies by itself, but in combination with suboptimal to optimal amounts of rhuGM-CSF enhanced the numbers and the size of CFU-GM colonies in an additive to greater than additive manner. While we did not detect an effect of MGF on CFU-G colony numbers stimulated by maximal concentrations of rhuG-CSF, MGF did enhance the size of CFU-G-derived colonies. MGF did not enhance the activity of rhuM-CSF. In a comparative assay, maximal concentrations of rmu and rhuMGF were equally effective in the enhancement of human bone marrow colony formation, but rhuMGF, in contrast to rmuMGF, did not at the concentrations tested enhance colony formation by mouse bone marrow cells. MGF effects on BFU-E, CFU-GM, and CFU-GEMM may be direct acting ones as MGF-enhanced colony formation by these cells in highly enriched progenitor cell populations of CD34 HLA-DR+ and CD34 HLA-DR+CD33- sorted cells in which greater than or equal to 1 of 2 cells was a BFU-E plus CFU-GM plus CFU-GEMM. MGF appears to be an early acting cytokine that preferentially stimulates the growth of immature hematopoietic progenitor cells.

scholarly journals The supportive effects of erythropoietin and mast cell growth factor on CD34+/CD36- sorted bone marrow cells of myelodysplasia patients

Blood ◽  
1996 ◽  
Vol 88 (2) ◽  
pp. 505-510 ◽  
Author(s):  
S Brada ◽  
J de Wolf ◽  
D Hendriks ◽  
M Esselink ◽  
M Ruiters ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Growth Factor ◽  
Cell Growth ◽  
Bone Marrow Cells ◽  
Early Stage ◽  
Erythroid Differentiation ◽  
Erythroid Development ◽  
Mast Cell Growth Factor ◽  
Marrow Cells

In the present study, we analyzed the capacity of CD34+/CD36- sorted bone marrow cells of myelodysplasia patients (n = 4) to differentiate along the erythroid lineage in the presence of erythropoietin (Epo) and mast cell growth factor (MGF). Two subgroups could be identified. In 6 patients, a normal number of burst-forming units-erythroid (BFU-Es) were cultured from CD34+/CD36- sorted cells. Cells from these patients did have the capacity to differentiate to colony-forming units- erythroid (CFU-Es) progenitors in cell suspension cultures with Epo plus MGF followed by Epo in the culture assay. Moreover, the cells became CD34-/CD36+/gly-cophorin A (GpA)+ after 7 days of culture with Epo plus MGF, a pattern comparable to that of normal progenitors. In contrast, in 8 patients, a different pattern was observed. No BFU-Es or a low number of BFU-Es were cultured from the CD34+/CD36- sorted cell fraction that was, in most of the cases, incapable of differentiating to CFU-E progenitors. Flow cytometry of the sorted population showed that, after 7 days of culture with Epo plus MGF, a high proportion of CD34+/CD36- cells persisted, whereas a low proportion of cells became CD34-/CD36+/GpA+. The unresponsiveness is not caused by the used growth factor combination, because the addition of interleukin-3 did not correct the defect. Evi-1 expression was studied in 9 cases to show whether an aberrant Evi-1 expression correlates with a disturbed erythroid development. Evi-1 expression was shown in 4 of 9 cases, whereas 3 of 9 cases did have a disturbed erythroid differentiation. In summary, the results show that the defects in the erythroid development in a subpopulation of patients with myelodysplasia is localized at an early stage of the erythroid differentiation and is associated with the persistent expression of the CD34 antigen and, in some cases, with the expression of Evi-1.

Nerve Growth Factor-Responsive Neuronal Progenitors From Human Umbilical Cord Blood.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4601-4601
Author(s):  
Arnon Nagler ◽  
Hadar Arien-Zakay ◽  
Shimon Lecht ◽  
Hanan Galski ◽  
Philip Lazarovici
Keyword(s):  
Bone Marrow ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Ngf Receptor ◽  
Trka Receptors

Abstract Abstract 4601 Background Nerve growth factor (NGF) is a well characterized neurotrophin required for the survival and differentiation of a variety of cell types in the peripheral and central nervous system. Over the last decade, many studies have demonstrated the physiological role of NGF in proliferation, differentiation and activation of different hematopoietic cells. Hematopoietic progenitors from bone marrow, umbilical cord blood and peripheral blood were found to be responsive to the actions of NGF. Furthermore, bone marrow stromal cells produce and respond to NGF during different steps of normal hematopoiesis. Results In this study, we describe a population of collagen-adherent, CD49a/b (á1/2 integrin receptors) and nestin-positive human umbilical cord blood derived progenitors. The identity of these cells was established as positive for the mesenchymal markers: CD13, CD29, CD44, CD49a,b, CD49e, CD73, CD105 and vimentin and negative for the hematopoietic markers: CD34, CD49c, CD49d, CD62e, CD62p, CD106, CD117, CD133, CD235a, HLA-DRB4 and HAS1, using Affimatrix™ human DNA chip technology, immunomagnetic sorting and Western blotting approaches. The NGF- receptor, TrkA, was found to be expressed upon isolation of these progenitors, but was gradually down-regulated upon 14 days growth in culture, as measured by mRNA, protein expression and binding properties. However, continuous presense of NGF in the culture media preserved the TrkA receptors expression. The pan-neurotrophin NGF receptor p75NTR, belonging to the TNF family of cell-death receptors, was not detected in the progenitors at any time. The effect of NGF on the cord blood progenitors global gene expression indicated highly increased expression of 170 genes, 24 and 20% of which were related to neuronal proliferation (NEK1, cyclin B1, EGR4, LGN, GATA6) or differentiation (AP2, Neurogenic differentiation factor 2, lamin B1, Ca(2+)-activated Cl- channel, Kv channel, GABA-A alpha 5 receptor, D2 dopamine receptor, neuropeptides precursor), respectively and strong reduction in the expression of 58 genes, 35% of which were hematopoiesis-related (CD7, T cell receptor alpha, interleukin 21 receptor, natural killer cell transcript 4, HLA-G, complement component1, defensin alpha1). Furthermore, upon treatment with NGF, the progenitors expressed a neuronal-like phenotype as evaluated by measurements of long neurite outgrowths and various developmental neuronal markers expression (MAP-2, NeuN neurofillament-160, beta-tubulin III, neuron specific enolase). These findings strongly suggest NGF-induced reprogramming of the cord blood derived progenitors towards neuronal differentiation commitment. The progenitors were also found to confer ∼35% neuroprotection to neurons exposed to an ischemic damage by a “bystander” effect mechanism, which includes the increased autocrine secretion of NGF and activation of TrkA receptors in the insulted neurons. Conclusions These results suggest an important role for NGF in regulating human umbilical cord blood neuronal progenitor's growth and reprogramming towards neuronal differentiation. In view of the broad spectrum of possible uses of cord blood in transplantations, we may also suggest that human umbilical cord blood and/or derived NGF-responsive progenitors may serve as a useful source of neuronal cells for cell therapy of neuropathological disorders. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Effect of murine mast cell growth factor (c-kit proto-oncogene ligand) on colony formation by human marrow hematopoietic progenitor cells

Blood ◽  
1991 ◽  
Vol 77 (10) ◽  
pp. 2142-2149 ◽  
Author(s):  
HE Broxmeyer ◽  
S Cooper ◽  
L Lu ◽  
G Hangoc ◽  
D Anderson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Growth Factor ◽  
Cell Growth ◽  
Progenitor Cells ◽  
Colony Formation ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Hla Dr ◽  
Mast Cell Growth Factor

Abstract Purified natural (n) and recombinant (r) murine (mu) mast cell growth factor (MGF, a c-kit ligand) were evaluated alone and in combination with r human (hu) erythropoietin (Epo), rhu granulocyte-macrophage colony-stimulating factor (rhuGM-CSF), rhuG-CSF, and/or rhuM-CSF for effects in vitro on colony formation by multipotential (colony-forming unit-granulocyte, erythroid, monocyte, megakaryocyte [CFU-GEMM]), erythroid (burst-forming unit erythroid [BFU-E]) and granulocyte- macrophage (CFU-GM) progenitor cells from normal human bone marrow. MGF was a potent enhancing cytokine for Epo-dependent CFU-GEMM and BFU-E colony formation, stimulating more colonies and of a larger size than either rhu interleukin-3 (rhuIL-3) or rhuGM-CSF. MGF, especially at lower concentrations, also acted with rhuIL-3 or rhuGM-CSF to enhance Epo-dependent CFU-GEMM and BFU-E colony formation. MGF had little stimulating activity for CFU-GM colonies by itself, but in combination with suboptimal to optimal amounts of rhuGM-CSF enhanced the numbers and the size of CFU-GM colonies in an additive to greater than additive manner. While we did not detect an effect of MGF on CFU-G colony numbers stimulated by maximal concentrations of rhuG-CSF, MGF did enhance the size of CFU-G-derived colonies. MGF did not enhance the activity of rhuM-CSF. In a comparative assay, maximal concentrations of rmu and rhuMGF were equally effective in the enhancement of human bone marrow colony formation, but rhuMGF, in contrast to rmuMGF, did not at the concentrations tested enhance colony formation by mouse bone marrow cells. MGF effects on BFU-E, CFU-GM, and CFU-GEMM may be direct acting ones as MGF-enhanced colony formation by these cells in highly enriched progenitor cell populations of CD34 HLA-DR+ and CD34 HLA-DR+CD33- sorted cells in which greater than or equal to 1 of 2 cells was a BFU-E plus CFU-GM plus CFU-GEMM. MGF appears to be an early acting cytokine that preferentially stimulates the growth of immature hematopoietic progenitor cells.

scholarly journals Mast cell growth factor modulates CD36 antigen expression on erythroid progenitors from human bone marrow and peripheral blood associated with ongoing differentiation

Blood ◽  
1994 ◽  
Vol 84 (1) ◽  
pp. 59-64 ◽  
Author(s):  
JT de Wolf ◽  
EW Muller ◽  
DH Hendriks ◽  
RM Halie ◽  
E Vellenga
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Growth Factor ◽  
Cell Growth ◽  
Peripheral Blood ◽  
Cell Fraction ◽  
Glycophorin A ◽  
Erythroid Progenitors ◽  
Colony Assay ◽  
Mast Cell Growth Factor

To study the differentiation process of erythroid progenitors from normal human bone marrow and peripheral blood, CD34/CD36 sorted cells were cultured in the presence of Erythropoietin (Epo) and Epo plus mast cell growth factor (MGF). The CD34+/CD36- cell fraction from bone marrow supported 74 +/- 33 erythroid burst forming units (BFU-E)/10(4) cells (mean +/- SD, n = 4) in the presence of Epo, which increased 2.1- fold by coculturing with MGF. However, erythroid colony-forming units (CFU-E) were not cultured from the CD34+/CD36- cell fraction. In contrast, the CD34-/CD36+ cell fraction supported CFU-Es in the presence of Epo (152 +/- 115/10(5)) or Epo plus MGF (180 +/- 112/10(5)), whereas BFU-Es were hardly noticed. However, the transition of the BFu-E to CFU-E was observed by incubating CD34+/CD36- cells (10(4)/100 microL) in suspension with Epo plus MGF for 7 days followed by Epo in the colony assay. This was reflected by the appearance of CD34-/CD36+/Glycophorin A+/CD14- cells. In addition high numbers of CFU- Es (1,000 +/- 150, n = 4) were cultured from this cell fraction. In contrast to bone marrow erythroid progenitors, no peripheral blood CFU- Es were cultured from either the CD36+ or CD36- fraction, whereas BFU- Es were predominantly present in the CD36+ fraction. However, the CD34+ progenitor cell from peripheral blood did have intrinsic capacity to differentiate to CFU-Es because CD34+/CD36- cells incubated with Epo plus MGF for 7 days and followed by Epo in the colony assay, supported high numbers of CFU-Es (1,200 +/- 400, n = 3). To study whether additional growth factors have similar effects on erythroid progenitors, experiments were performed with interleukin 1 (IL-1), IL- 3, and IL-6. IL-1 and IL-6 did not modulate the Epo supported proliferation and differentiation. In contrast, IL-3 in the presence of Epo did support CFU-Es, from CD34+/CD36- cells after 7 days in suspension culture. However, flow cytometry analysis showed that Epo plus IL-3 not only supported CD34-/CD36+/Glycophorin A+ cells but also CD36+/CD14+ cells, indicating the differentiation along different cell lineages. In summary, the data show a phenotypic distinction between bone marrow and peripheral blood erythroid progenitors with regard to CD36 expression. In addition, the results suggest that Epo plus MGF or IL-3 and preincubation in suspension culture are prerequisites for the transition of the BFU-E to the CFU-E.

scholarly journals Mast cell growth factor modulates CD36 antigen expression on erythroid progenitors from human bone marrow and peripheral blood associated with ongoing differentiation

Blood ◽  
1994 ◽  
Vol 84 (1) ◽  
pp. 59-64 ◽  
Author(s):  
JT de Wolf ◽  
EW Muller ◽  
DH Hendriks ◽  
RM Halie ◽  
E Vellenga
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Growth Factor ◽  
Cell Growth ◽  
Peripheral Blood ◽  
Cell Fraction ◽  
Glycophorin A ◽  
Erythroid Progenitors ◽  
Colony Assay ◽  
Mast Cell Growth Factor

Abstract To study the differentiation process of erythroid progenitors from normal human bone marrow and peripheral blood, CD34/CD36 sorted cells were cultured in the presence of Erythropoietin (Epo) and Epo plus mast cell growth factor (MGF). The CD34+/CD36- cell fraction from bone marrow supported 74 +/- 33 erythroid burst forming units (BFU-E)/10(4) cells (mean +/- SD, n = 4) in the presence of Epo, which increased 2.1- fold by coculturing with MGF. However, erythroid colony-forming units (CFU-E) were not cultured from the CD34+/CD36- cell fraction. In contrast, the CD34-/CD36+ cell fraction supported CFU-Es in the presence of Epo (152 +/- 115/10(5)) or Epo plus MGF (180 +/- 112/10(5)), whereas BFU-Es were hardly noticed. However, the transition of the BFu-E to CFU-E was observed by incubating CD34+/CD36- cells (10(4)/100 microL) in suspension with Epo plus MGF for 7 days followed by Epo in the colony assay. This was reflected by the appearance of CD34-/CD36+/Glycophorin A+/CD14- cells. In addition high numbers of CFU- Es (1,000 +/- 150, n = 4) were cultured from this cell fraction. In contrast to bone marrow erythroid progenitors, no peripheral blood CFU- Es were cultured from either the CD36+ or CD36- fraction, whereas BFU- Es were predominantly present in the CD36+ fraction. However, the CD34+ progenitor cell from peripheral blood did have intrinsic capacity to differentiate to CFU-Es because CD34+/CD36- cells incubated with Epo plus MGF for 7 days and followed by Epo in the colony assay, supported high numbers of CFU-Es (1,200 +/- 400, n = 3). To study whether additional growth factors have similar effects on erythroid progenitors, experiments were performed with interleukin 1 (IL-1), IL- 3, and IL-6. IL-1 and IL-6 did not modulate the Epo supported proliferation and differentiation. In contrast, IL-3 in the presence of Epo did support CFU-Es, from CD34+/CD36- cells after 7 days in suspension culture. However, flow cytometry analysis showed that Epo plus IL-3 not only supported CD34-/CD36+/Glycophorin A+ cells but also CD36+/CD14+ cells, indicating the differentiation along different cell lineages. In summary, the data show a phenotypic distinction between bone marrow and peripheral blood erythroid progenitors with regard to CD36 expression. In addition, the results suggest that Epo plus MGF or IL-3 and preincubation in suspension culture are prerequisites for the transition of the BFU-E to the CFU-E.

scholarly journals Cytokines in chronic inflammatory arthritis. I. Failure to detect T cell lymphokines (interleukin 2 and interleukin 3) and presence of macrophage colony-stimulating factor (CSF-1) and a novel mast cell growth factor in rheumatoid synovitis.

1988 ◽  
Vol 168 (5) ◽  
pp. 1573-1586 ◽  
Author(s):  
G S Firestein ◽  
W D Xu ◽  
K Townsend ◽  
D Broide ◽  
J Alvaro-Gracia ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Growth Factor ◽  
Cell Growth ◽  
Synovial Tissue ◽  
Thymidine Uptake ◽  
Colony Stimulating Factor ◽  
Sephadex Column ◽  
Stimulating Factor ◽  
Mast Cell Growth Factor

Because previous studies showed low levels of IFN-gamma in rheumatoid arthritis (RA) synovial fluid (SF) and synovial tissue (ST) explant supernatants, we assayed RA SF and ST for IL-2 and IL-3-like activity. Using an IL-2 dependent murine CTLL line, 6 of 14 RA SF caused increased thymidine uptake (greater than three times control). The activity was distinct from IL-2 because it was not blocked by antibody to IL-2-R. In addition, IL-2 was not detected (less than 50 pg/ml) in 16 joint samples using an ELISA. Multi-colony-stimulating factor (CSF) activity was measured using two assays that can detect murine IL-3 (mast cell proliferation, and bone marrow CSF). In the mast cell assay, [3H]TdR uptake was 493 +/- 67 cpm for medium, 2,910 +/- 329 cpm in the presence of RA SF (p less than 0.001), 1,246 +/- 156 cpm in the presence of SF from patients with seronegative spondyloarthropathies (p less than 0.001), and 736 +/- 100 cpm in the presence of osteoarthritis SF (p greater than 0.1). In the CSF assay, four of five RA SF and five of five RA ST induced colony formation from bone marrow nonadherent cells. Macrophage colonies were most common, although mixed colonies and granulocytes were occasionally observed. The multi-CSF activity in RA is not due to IL-3 since human rIL-3 was not active in either murine assay, and IL-3 mRNA was not detected in RA synovium. Sephadex column chromatography of RA SF revealed that the mast cell growth factor (approximately 6 x 10(3) mol wt) and the CSF (approximately 40 and 100 x 10(3) mol wt) are distinct. The colony-stimulating aspect of the "IL-3-like" activity in RA SF is likely due to CSF-1 because it is the appropriate mol wt and because the activity was neutralized by specific anti-CSF-1 antibody. Finally, an RIA detected 1.6-25 ng/ml of CSF-1 in RA SF and ST and CSF-1 mRNA was detected in four of five RA synovial tissue samples tested.

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