Traditional Chinese Whole-Body Acupuncture Mobilizes CD133(+)CD34(−) Cells

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5405-5405
Author(s):  
Sonja Moldenhauer ◽  
Miriam Burgauner ◽  
Rainer Hellweg ◽  
Andreas Lun ◽  
Holger Kiesewetter ◽  
...  
Keyword(s):  
Serum Levels ◽  
Whole Body ◽  
Granulocyte Colony Stimulating Factor ◽  
Serum Concentrations ◽  
Spinal Cord Lesions ◽  
Blood Samples ◽  
Cd34 Cells ◽  
Body Acupuncture ◽  
Study Participants ◽  
Stimulating Factor

Abstract The objective of this study was to analyze the effects of traditional Chinese acupuncture for spinal cord lesions on the mobilization of stem cells. Therefore, 14 healthy study participants were acupunctured and gave blood samples before, immediately after as well as 24 and 48 hours after acupuncture. At these time points, the frequency of CD133, CD34, CD4, CD14, CD19 and CD45 positive cells were determined by flow cytometry. Furthermore, serum concentrations of matrix metalloproteinases (MMP) 8 and 9, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), stroma-derived factor (SDF) 1 and granulocyte-colony stimulating factor (G-CSF) were measured by enzyme-linked immunosorbent assays. CD133(+)34(−) cells were significantly increased 48 hours after acupuncture (29.1±5.8% versus 11.4±4.8%, p= 0.015), which was paralleled by significant decreases of BDNF (7.5±1 ng/ml versus 10.8±1.6 ng/ml, p= 0.013) and MMP-9 serum levels (46.4±2.6ng/ml versus 42.5±2.4 ng/ml, p= 0.009). Values in non-treated controls were not affected. No changes in SDF-1, NGF, interleukin-6 and G-CSF concentrations occurred. In conclusion, acupuncture does mobilize non-hematopoietic CD133(+) cells.

scholarly journals Prevention of Thrombocytopenia and Neutropenia in a Nonhuman Primate Model of Marrow Suppressive Chemotherapy by Combining Pegylated Recombinant Human Megakaryocyte Growth and Development Factor and Recombinant Human Granulocyte Colony-Stimulating Factor

Blood ◽  
1997 ◽  
Vol 89 (1) ◽  
pp. 155-165 ◽  
Author(s):  
Laurence A. Harker ◽  
Ulla M. Marzec ◽  
Andrew B. Kelly ◽  
Ellen Cheung ◽  
Aaron Tomer ◽  
...  
Keyword(s):  
Platelet Count ◽  
Neutrophil Count ◽  
Growth And Development ◽  
Granulocyte Colony Stimulating Factor ◽  
Serum Concentrations ◽  
Colony Stimulating Factor ◽  
Platelet Counts ◽  
Development Factor ◽  
Trough Serum ◽  
Stimulating Factor

Abstract This report examines the effects on hematopoietic regeneration of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF ) (2.5 μg/kg/d) alone and in combination with recombinant human granulocyte colony stimulating factor (rHu-GCSF ) (10 μg/kg/d) for 21 days in rhesus macaques receiving intense marrow suppression produced by single bolus injections of hepsulfam (1.5 g/m2). In six hepsulfam-only control animals thrombocytopenia (platelet count <100 × 109/L) was observed between days 12 and 25 (nadir 39 ± 20 × 109/L on day 17), and neutropenia (absolute neutrophil count <1 × 109/L) occurred between days 8 and 30 (nadir 0.167 ± 0.120 × 109/L on day 15). PEG-rHuMGDF (2.5 μg/kg/d) injected subcutaneously into four animals from day 1 to day 22 following hepsulfam administration produced trough serum concentrations of 1.9 ± 0.2 ng/mL and increased the platelet count twofold over basal prechemotherapy levels (856 ± 594 × 109/L v baseline of 416 ± 88 × 109/L; P = .01). PEG-rHuMGDF alone also shortened the period of posthepsulfam neutropenia from 22 days to 12 days (P = .01), although the neutropenic nadir was not significantly altered (neutrophil count 0.224 ± 0.112 × 109/L v 0.167 ± 0.120 × 109/L; P < .3). rHu-GCSF (10 μg/kg/d) injected subcutaneously into four animals from day 1 to day 22 following hepsulfam administration produced trough serum concentrations of 1.4 ± 1.1 ng/mL, and reduced the time for the postchemotherapy neutrophil count to attain 1 × 109/L from 22 days to 4 days (P = .005). The postchemotherapy neutropenic nadir was 0.554 ± 0.490 × 109neutrophils/L (P = .3 v hepsulfam-only control of 0.167 ± 0.120 × 109/L). However, thrombocytopenia of <100 × 109 platelets/L was not shortened (persisted from day 12 to day 25), or less severe (nadir of 56 ± 32 × 109 platelets/L on day 14; P = .7 compared with untreated hepsulfam animals). The concurrent administration of rHu-GCSF (10 μg/kg/d) and PEG-rHuMGDF (2.5 μg/kg/d) in four animals resulted in postchemotherapy peripheral platelet counts of 127 ± 85 × 109/L (P = .03 compared with 39 ± 20 × 109/L for untreated hepsulfam alone, and P = .02 compared with 856 ± 594 × 109/L for PEG-rHuMGDF alone), and shortened the period of neutropenia <1 × 109/L from 22 days to 4 days (P = .8 compared with rHu-GCSF alone). Increasing PEG-rHuMGDF to 10 μg/kg/d and maintaining the 21-day schedule of coadministration with rHu-GCSF (10 μg/kg/d) in another four animals produced postchemotherapy platelet counts of 509 ± 459 × 109/L (P < 10−4compared with untreated hepsulfam alone, and P = .04 compared with 2.5 μg/kg/d PEG-rHuMGDF alone), and 4 days of neutropenia. Coadministration of rHu-GCSF and PEG-rHuMGDF did not significantly alter the pharmacokinetics of either agent. The administration of PEG-rHuMGDF (2.5 μg/kg/d) from day 1 through day 22 and rHu-GCSF (10 μg/kg/d) from day 8 through day 22 in six animals produced peak postchemotherapy platelet counts of 747 ± 317 × 109/L (P < 10−4 compared with untreated hepsulfam alone, and P = .7 compared with PEG-rHuMGDF alone), and maintained the neutrophil count < 3.5 × 109/L (P = .008 v rHu-GCSF therapy alone). Thus, both thrombocytopenia and neutropenia are eliminated by initiating daily PEG-rHuMGDF therapy on day 1 and subsequently adding daily rHu-GCSF after 1 week in the rhesus model of hepsulfam marrow suppression. This improvement in platelet and neutrophil responses by delaying the addition of rHu-GCSF to PEG-rHuMGDF therapy demonstrates the importance of optimizing the dose and schedule of cytokine combinations after severe myelosuppressive chemotherapy.

scholarly journals Can granulocyte colony stimulating factor (G-CSF) ameliorate acetaminophen-induced hepatotoxicity?

2021 ◽  
pp. 096032712110085
Author(s):  
EA Ahmed ◽  
AM Abd-Eldayem ◽  
E Ahmed
Keyword(s):  
Liver Damage ◽  
Liver Toxicity ◽  
Serum Levels ◽  
Hepatic Tissue ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Oxidative Markers ◽  
Stimulating Factor ◽  
New Strategies ◽  
Factor G

Acetaminophen (APAP) is often used as an antipyretic and analgesic agent. Overdose hepatotoxicity, which often results in liver cell failure and liver transplantation, is a severe complication of APAP usage. To save the liver and save lives from acute liver damage caused by APAP, the search for new strategies for liver defense is important. Wistar rats have been used for the induction of APAP hepatotoxicity. Elevated levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were evaluated for liver toxicity. In addition, the levels of hepatic tissue oxidative markers such as malondialdehyde (MDA), nitric oxide (NO) increased while glutathione (GSH) was depleted and catalase (CAT) activity was curtailed. The biochemical findings were consistent with the changes in histology that suggested liver damage and inflammation. Treated rats with N-acetylcysteine (N-AC) and granulocyte colony stimulating factor (G-CSF) showed a decrease in serum levels of ALT, AST and LDH, while the level of ALP in the G-CSF group was still high. After administration of APAP, treatment with N-AC or G-CSF substantially reduced the level of MDA and NO while maintaining the GSH content and CAT activity. Treatment with N-AC and G-CSF after administration of APAP has also attenuated inflammation and hepatocytes necrosis. The results of this study showed that G-CSF could be viewed as an alternative hepatoprotective agent against APAP-induced acute liver injury compared to N-AC.

scholarly journals Preclinical immunogenicity testing using anti-drug antibody analysis of GX-G3, Fc-fused recombinant human granulocyte colony-stimulating factor, in rat and monkey models

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yun Jung Kim ◽  
Eun Mi Koh ◽  
Chi Hun Song ◽  
Mi Sun Byun ◽  
Yu Ri Choi ◽  
...  
Keyword(s):  
Recovery Period ◽  
White Blood Cells ◽  
Serum Levels ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Serum Samples ◽  
Toxicological Studies ◽  
Validation Parameters ◽  
Immunogenicity Assessment ◽  
Stimulating Factor

AbstractHuman granulocyte colony-stimulating factor (G-CSF, this study used Fc-fused recombinant G-CSF; GX-G3) is an important glycoprotein that stimulates the proliferation of granulocytes and white blood cells. Thus, G-CSF treatment has been considered as a crucial regimen to accelerate recovery from chemotherapy-induced neutropenia in cancer patients suffering from non-myeloid malignancy or acute myeloid leukemia. Despite the therapeutic advantages of G-CSF treatment, an assessment of its immunogenicity must be performed to determine whether the production of anti-G-CSF antibodies causes immune-related disorders. We optimized and validated analytical tools by adopting validation parameters for immunogenicity assessment. Using these validated tools, we analyzed serum samples from rats and monkeys injected subcutaneously with GX-G3 (1, 3 or 10 mg/kg once a week for 4 weeks followed by a 4-week recovery period) to determine immunogenicity response and toxicokinetic parameters with serum concentration of GX-G3. Several rats and monkeys were determined to be positive for anti-GX-G3 antibodies. Moreover, the immunogenicity response of GX-G3 was lower in monkeys than in rats, which was relevant to show less inhibition of toxicokinetic profiles in monkeys, at least 1 mg/kg administrated group, compared to rats. These results suggested the establishment and validation for analyzing anti-GX-G3 antibodies and measurement of serum levels of GX-G3 and anti-GX-G3 antibodies, which was related with toxicokinetic profiles. Taken together, this study provides immunogenicity assessment which is closely implicated with toxicokinetic study of GX-G3 in 4-week repeated administrated toxicological studies.

Granulocyte Colony–Stimulating Factor Mobilizes CD34+ Cells and Improves Survival of Patients With Acute-on-Chronic Liver Failure

2012 ◽  
Vol 142 (3) ◽  
pp. 505-512.e1 ◽  
Author(s):  
Vishal Garg ◽  
Hitendra Garg ◽  
Arshi Khan ◽  
Nirupama Trehanpati ◽  
Ashish Kumar ◽  
...  
Keyword(s):  
Liver Failure ◽  
Chronic Liver ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Chronic Liver Failure ◽  
Cd34 Cells ◽  
Stimulating Factor

Effect of different chemotherapy regimens on peripheral-blood stem-cell collections in patients with breast cancer receiving granulocyte colony-stimulating factor.

1997 ◽  
Vol 15 (2) ◽  
pp. 684-690 ◽  
Author(s):  
T Demirer ◽  
C D Buckner ◽  
B Storer ◽  
K Lilleby ◽  
S Rowley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Reference Group ◽  
Blood Stem Cell ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Cd34 Cells ◽  
Stimulating Factor

PURPOSE To evaluate the effects of chemotherapy regimens on peripheral-blood stem-cell (PBSC) yields in patients with breast cancer who receive granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHODS One hundred patients with breast cancer received cyclophosphamide 4 g/m2 for dose (CY) (n = 10), CY and etoposide 600 mg/m2 (CE) (n = 13), CE and cisplatin 105 mg/m2 (CEP) (n = 19), or CY and paclitaxel 170 mg/m2 (n = 58), followed by G-CSF. PBSC collections were initiated when the WBC count recovered to greater than 1 x 10(9)/L. A multivariate analysis was undertaken to evaluate the effects of different chemotherapy regimens and patient variables on PBSC collections as measured by the yield of CD34+ cells. RESULTS The medians of average daily CD34+ cell yields for patients who received paclitaxel plus CY, CE, and CEP with G-CSF were 12.9, 11.03, and 5.37 x 10(6)/kg, respectively, compared with 2.02 x 10(6)/kg in the reference group that received CY with G-CSF (P = < .0001, .002, and .09, respectively). On first-day collections, patients who received paclitaxel plus CY, CE, and CEP with G-CSF yielded medians of 11.07, 8.09, and 3.52 x 10(6) CD34+ cells/kg, respectively, compared with 0.90 x 10(6)/kg in the reference group that received CY with G-CSF (P = .0006, .02, and .09, respectively). The number of previous cycles of chemotherapy, previous radiotherapy, marrow involvement, and phase and stage of disease did not have statistically significant effects on CD34+ cell yield. CONCLUSION Combination chemotherapy regimens were superior to single-agent CY for the mobilization of CD34+ cells.

scholarly journals Production of granulocyte colony-stimulating factor in vitro by monocytes from preterm and term neonates [see comments]

Blood ◽  
1993 ◽  
Vol 82 (8) ◽  
pp. 2478-2484 ◽  
Author(s):  
KR Schibler ◽  
KW Liechty ◽  
WL White ◽  
RD Christensen
Keyword(s):  
Newborn Infants ◽  
Preterm Neonates ◽  
Granulocyte Colony Stimulating Factor ◽  
Serum Concentrations ◽  
Colony Stimulating Factor ◽  
Term Infants ◽  
Term Neonates ◽  
And Function ◽  
Stimulating Factor

Abstract We postulated that defective generation of granulocyte colony- stimulating factor (G-CSF) by cells of newborn infants might underlie their deficiencies in upregulating neutrophil production and function during bacterial infection. To test this, we isolated monocytes from the blood of preterm neonates, term neonates, and adults and, after stimulation with various concentrations of interleukin-1 alpha (IL-1 alpha) or lipopolysaccharide (LPS), quantified G-CSF concentrations in cell supernatants and G-CSF mRNA in cell lysates. When stimulated with plateau concentrations of IL-1 alpha for 24 hours, G-CSF concentrations were higher in supernatants of adult cells (8,699 +/- 5,529 pg/10(6) monocytes) than in those from term infants (2,557 +/- 442 pg, P < .05) or from preterm infants (879 +/- 348 pg, P < .05 v adults). When stimulated with plateau concentrations of LPS, supernatants of monocytes from preterm neonates had less G-CSF than did those from term neonates or adults. G-CSF mRNA content was low in cells from preterm infants, higher in those from term infants, and highest in those from adults. On the basis of the in vitro studies, we speculated that serum G-CSF concentrations might be less elevated in neutropenic neonates than in neutropenic adults. Indeed, serum concentrations were relatively low in all nonneutropenic subjects; 92 +/- 34 pg/mL (mean +/- SEM) in 10 preterm neonates, 114 +/- 21 pg/mL in 16 term neonates, and 45 +/- 13 pg/mL in 11 healthy adults. Serum concentrations were not elevated in 7 neutropenic neonates (39 +/- 17 pg/mL) but were in 8 neutropenic adults (2101 +/- 942 pg/mL, P < .05 v healthy adults). Other studies suggested that the lower G-CSF production in neonates is not counterbalanced by a heightened sensitivity of G-CSF--responsive progenitors to G-CSF. Therefore, we speculate that newborn infants, particularly those delivered prematurely, generate comparatively low quantities of G-CSF after inflammatory stimulation, and that this might constitute part of the explanation for their defective upregulation of neutrophil production and function during infection.

scholarly journals Serum Levels of Neuropeptides in Cows with Left Abomasal Displacement

2018 ◽  
Vol 5 (4) ◽  
pp. 103
Author(s):  
Marlene Sickinger ◽  
Joachim Roth ◽  
Klaus Failing ◽  
Axel Wehrend
Keyword(s):  
Substance P ◽  
Dairy Cows ◽  
Vasoactive Intestinal Polypeptide ◽  
Serum Levels ◽  
Common Disease ◽  
Healthy Controls ◽  
Serum Concentrations ◽  
Blood Samples ◽  
Breed Difference ◽  
Abomasal Displacement

Abomasal displacement (AD) to the left is a common disease in high-yielding dairy cows after parturition. In view of the previously reported changes in tissue neuropeptide concentrations in cows with AD, the primary aim of this study was to evaluate the effect of AD and breed on serum neuropeptide concentrations. For this purpose, blood samples of 33 German Holstein (GH) cows with AD, 36 healthy controls (GH), and 32 healthy German Fleckvieh (GF) cows were collected, and concentrations of substance P (SP), vasoactive intestinal polypeptide (VIP), and interleukin1β (IL-1β) were measured via commercially available ELISA kits. To examine the effect of AD, we compared GH cows with and without AD and observed no significant effects of AD on SP, VIP, or Il-1 β concentrations. To evaluate the effect of breed, we compared healthy GH with healthy GF cows and detected markedly higher VIP serum levels in the healthy GF cows (p < 0.01). No significant differences in SP or IL-1β were detected. According to our results, there seems to be no effect of AD on the serum concentrations of SP, VIP, or IL-1 β. In contrast, there seems to be a breed difference concerning serum VIP concentrations.

scholarly journals Target cells for granulocyte colony-stimulating factor, interleukin-3, and interleukin-5 in differentiation pathways of neutrophils and eosinophils

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 1956-1961 ◽  
Author(s):  
H Ema ◽  
T Suda ◽  
K Nagayoshi ◽  
Y Miura ◽  
CI Civin ◽  
...  
Keyword(s):  
Bone Marrow Cells ◽  
Early Stage ◽  
Target Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Interleukin 3 ◽  
Cd34 Antigen ◽  
Cd34 Cells ◽  
Stimulating Factor

Abstract To study the relationship between hematopoietic factors and their responsive hematopoietic progenitors in the differentiation process, both purified factors and enriched progenitors are required. We isolated total CD34+ cells, CD34+,CD33+ cells, and CD34+,CD33- cells individually from normal human bone marrow cells by fluorescence- activated cell sorter (FACS), and examined the effects of granulocyte colony-stimulating factor (G-CSF), interleukin-3 (IL-3), and IL-5 on in vitro colony formation of these cells. CD34+,CD33+ cells formed granulocyte colonies in the presence of G-CSF. Both CD34+,CD33+ cells and CD34+,CD33- cells formed granulocyte/macrophage colonies in the presence of IL-3. Eosinophil (Eo) colonies were only formed by CD34+,CD33- cells in response to IL-3, but scarcely formed by CD34+ cells in the presence of IL-5. We performed the two-step cultures consisting of the primary liquid culture for 6 days and the secondary methylcellulose culture, and serially examined changes in phenotypes of ,he cells cultured in the primary culture. CD34-,CD33+ cells derived from CD34+,CD33+ cells by preincubation with G-CSF or IL-3 formed Eo colonies in the presence of IL-5 but not IL-3. CD34-,CD33+ cells derived from CD34+,CD33- cells by preincubation with IL-3 also formed Eo colonies by support of IL-5 as well as IL-3. Both CD34+ cells gradually lost the CD34 antigen by day 6 of incubation with G-CSF or IL- 3. Loss of this antigen was well-correlated with acquisition of susceptibility to IL-5. It was concluded that G-CSF supported the neutrophil differentiation of committed colony-forming cells, IL-3 supported that of both committed and multipotent colony-forming cells. G-CSF and IL-3 also supported the early stage of E. differentiation; IL- 5 supported the late stage of that.

Granulocyte colony-stimulating factor crosses the placenta and stimulates fetal rat granulopoiesis

Blood ◽  
1993 ◽  
Vol 81 (4) ◽  
pp. 916-922 ◽  
Author(s):  
ES Medlock ◽  
DL Kaplan ◽  
M Cecchini ◽  
TR Ulich ◽  
J del Castillo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myeloid Cells ◽  
Serum Levels ◽  
Polymorphonuclear Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Pregnant Rats ◽  
Cell Counts ◽  
Fetal Serum ◽  
Stimulating Factor

Abstract We studied the effect of recombinant human granulocyte colony- stimulating factor (rhG-CSF) administration to pregnant rats upon fetal and neonatal myelopoiesis. Pregnant rats were treated with rhG-CSF twice daily for 2, 4, and 6 days before parturition. rhG-CSF crossed the placenta and reached peak fetal serum concentrations 4 hours after administration. Peak fetal serum levels were 1,000-fold lower than levels detected in the dam. Hematopoietic effects of rhG-CSF were assessed by cytologic analysis of the newborn blood, spleen, bone marrow, thymus, and liver. White blood cell counts were increased twofold to fourfold in newborns. This increase was due to circulating numbers of polymorphonuclear cells (PMN). rhG-CSF induced a myeloid hyperplasia in the newborn marrow consisting of immature and mature myeloid cells in the day-2 and day-4 treated pups. Bone marrow of pups treated for 6 days contained mostly hyper-segmented PMN with little or no increase in myeloid precursors. An increase in the number of postmitotic (PMN, bands, and metamyelocytes) and mitotic (promyeloblasts, myeloblasts, and metamyeloblasts) myeloid cells in the spleen of neonates was observed. No change was detected in splenic lymphocytes or monocytes. No effect of rhG-CSF was noted in the newborn liver or thymus. These results demonstrate that maternally administered rhG-CSF crosses the placenta and specifically induces bone marrow and spleen myelopoiesis in the fetus and neonate. The significant myelopoietic effects of rhG-CSF at low concentrations in the fetus suggest an exquisite degree of developmental sensitivity to this cytokine and may provide enhanced defense mechanisms to the neonate.

scholarly journals Proliferative responses to interleukin-3 and granulocyte colony- stimulating factor distinguish a minor subpopulation of CD34-positive marrow progenitors that do not express CD33 and a novel antigen, 7B9

Blood ◽  
1991 ◽  
Vol 77 (11) ◽  
pp. 2354-2359 ◽  
Author(s):  
MR Litzow ◽  
C Brashem-Stein ◽  
RG Andrews ◽  
ID Bernstein
Keyword(s):  
Culture System ◽  
Liquid Culture ◽  
Thymidine Uptake ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Differentiation Antigens ◽  
Interleukin 3 ◽  
Cd34 Cells ◽  
Synergistic Response ◽  
Stimulating Factor

Abstract Human hematopoietic colony-forming cells (CFC) express the CD34 antigen (CD34+) as well as differentiation antigens such as CD33 and HLA-DR. CD34+ cells that do not express these latter differentiation antigens have been shown to contain few CFC in direct culture, but generate increasing numbers of CFC when cultured over a marrow stromal cell layer in the long-term culture system. In this study we determined if CD34+ cells with low or absent expression of CD33 and a novel antigen, 7B9 (CD34+CD33–7B9-), could be distinguished from CD34+ cells expressing these antigens (CD34+CD33+7B9+) based on their proliferative responses to interleukin-3 (IL-3) and granulocyte colony-stimulating factor (G-CSF) in a short-term liquid culture system. These two populations were separated by fluorescence-activated cell sorting, cultured with IL-3 (10 ng/mL), G-CSF (100 ng/mL), or IL-3 and G-CSF, and 3H-thymidine uptake was measured. CD34+CD33–7B9- cells proliferated in the presence of IL-3, but not G-CSF. However, a synergistic response to the combination of IL-3 and G-CSF was seen in most experiments. In contrast, CD34+CD33+7B9+ cells proliferated in the presence of either IL-3 or G-CSF but did not display an additive or synergistic response to the combination of IL-3 and G-CSF. In colony-forming assays performed before and after liquid culture, the CD34+CD33–7B9- cells in two experiments contained 0.3% and 2.2% of all sorted marrow CFC before liquid culture and generated 40-fold and ninefold increases in the number of granulocyte-macrophage colony-forming units (CFU-GM), respectively, after liquid culture with IL-3 and G-CSF. In contrast, the CD34+CD33+7B9+ cells contained 99.7% and 97.8% of all sorted marrow CFC before liquid culture and had no change or a threefold increase in the number of CFU-GM, respectively, after liquid culture with IL-3 and G-CSF. Single-cell liquid cultures containing IL-3 and G-CSF with cells that were either CD34+CD33–7B9- and depleted of mature lymphoid cells (CD34+lin-) or were CD34+lin+ showed that a higher proportion of wells containing a CD34+lin- cell gave rise to one or more CFC (8.7%) than did wells containing a CD34+lin+ cell (2.9%), with the responding cells in the former population giving rise to an average of 2.9 +/- 0.6 CFC and in the latter population, 2.0 +/- 1.0 CFC.(ABSTRACT TRUNCATED AT 400 WORDS)

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