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Results for “Granulocyte Precursor Cells”

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PubMed1999

Expression and role of PML gene in normal adult hematopoiesis: functional interaction between PML and Rb proteins in erythropoiesis.

The expression of the PML gene was investigated in purified early hematopoietic progenitor cells (HPCs) induced to unilineage erythroid or granulocytic differentiation. PML mRNA and protein, while barely detectable in quiescent HPCs, are consistently induced by growth factor stimulation through the erythroid or granulocytic lineage. Thereafter, PML is downmodulated in late granulocytic maturation, whereas it is sustainably expressed through the erythroid pathway. In functional studies, PML expression was inhibited by addition of antisense oligomers targeting PML mRNA (alpha-PML). Interestingly, early treatment (day 0 HPCs) with alpha-PML reduced the number of both erythroid and granulocytic colonies, whereas late treatment (day 5 culture) reduced erythroid, but not granulocytic, clonogenesis. These findings suggest that PML is required for early hematopoiesis and erythroid, but not granulocytic maturation. The pattern of PML expression in normal hematopoiesis mimics that of retinoblastoma pRb 105. Combined treatment of HPCs with alpha-PML and alpha-Rb oligomers inhibited both PML and Rb protein expression and completely blocked erythroid colony development. Furthermore, PML and pRb 105 were co-immunoprecipitated in cellular lysates derived from erythroid precursors indicating that this functional interaction may have a biochemical basis. These results suggest a key functional role of PML in early hematopoiesis and late erythropoiesis: the latter phenomenon may be related to the molecular and functional interaction of PML with pRb 105.

Adult↗

PubMed1977

Esterase activity in erythroleukemia.

Specific esterase activity, a property generally ascribed to cells of granulocytic origin, was found in abnormal erythroid precursors obtained from the bone marrows of six patients with untreated erythroleukemia. These erythroblasts also showed nonspecific esterase activity. Neither specific nor nonspecific esterase activity was detected in erythroid precursors obtained from the bone marrows of ten presumed normal individuals. The implications of finding specific esterase activity in the erythroblasts of erythroleukemia are discussed.

Erythroblasts↗

PubMed1984

Characterization of human bone marrow long-term cultures.

In an attempt to more closely simulate the native hematopoietic environment, human bone marrow bony matrix was cultivated in long-term human bone marrow cultures. Sternal bone marrow curettings (i.e., 'bony matrix') were cultured with and without autologous bone marrow single cell suspensions. Fresh media were provided at weekly intervals and the 'harvested' cells were assayed for CFU-gm (i.e., the granulocyte-macrophage precursor). Bone marrow bony matrix alone was not competent to maintain CFU-gm production, although early in the culture nucleated cells and CFU-gm were recruited from the bony matrix. A dose of 850 rad of X-radiation to the bone marrow matrix damaged the hematopoietic growth-promoting effects of the adherent cell layer, which was, however, rapidly reconstituted by an inoculation of intact autologous bone marrow cells. Additional investigations revealed that, whereas the addition of hydrocortisone to this culture system did not alter the maintenance of CFU-gm, recharging the cultures with fresh autologous marrow maintained CFU-gm for 10 weeks. These data indicate that human bone marrow stroma is more sensitive to X-irradiation in vitro than in vivo, and the bone marrow hematopoietic microenvironment provided by its bony matrix seemed to be less effective in vitro than in vivo with respect to the maintenance of hematopoietic precursor cells.

Adult↗

PubMed1992

Macrophages (phagocytic-histiocytic reticular cells) in reactive-inflammatory lesions of the bone marrow and in myelodysplastic syndromes (MDS). An immunohistochemical and morphometric study by use of a new monoclonal antibody (PG-M1).

An immunohistochemical and morphometric study was performed on trephine biopsies of the bone marrow in 52 patients (28 males/24 females; age 68 years) with various subtypes of myelodysplastic syndromes (MDS) to determine the number of macrophages (phagocytic-histiocytic reticular cells). Quantifications included the haemosiderin-storing subpopulation (Prussian-blue reaction) of this lineage as well as the iron-free compartment. The latter was identified by a new monoclonal antibody (PG-M1) which is specifically directed against histiocytic reticular cells. Bone marrow specimens of individuals without haematological disorders and those showing reactive lesions served as controls. In comparison with the normal bone marrow and inflammatory changes (i.e. rheumatoid arthritis) 23 of the 52 patients with MDS revealed a significant increase in macrophages. This increase encompassed not only the iron-laden subpopulation but also the total number of phagocytic reticular cells. Accumulation of macrophages in MDS was speculated to be due to a premature and enforced degradation of dysplastic cell elements leading to phagocytosis of haemosiderin and debris material. Moreover, cells of the monocyte-macrophage system could be involved in the complex pathomechanism of fibrillogenesis, since in a considerable percentage of patients with MDS, an increase in reticulin (argyrophilic) fibres was noticeable. Our finding of an expansion of the macrophage compartment in about half of the patients with MDS is in keeping with results of cell culture studies on colony formation of granulocyte-macrophage precursors (CFU-GM).

Adult↗

PubMed2000

AML1-MTG8 leukemic protein induces the expression of granulocyte colony-stimulating factor (G-CSF) receptor through the up-regulation of CCAAT/enhancer binding protein epsilon.

The t(8;21) translocation is one of the most frequent chromosomal abnormalities associated with acute myeloid leukemia (AML). In this translocation, the AML1 (CBFA2/PEBP2aB) gene is disrupted and fused to the MTG8 (ETO) gene. The ectopic expression of the resulting AML1-MTG8 fusion gene product in L-G and 32Dcl3 murine myeloid precursor cells stimulates cell proliferation without inducing morphologic terminal differentiation into mature granulocytes in response to granulocyte-colony stimulating factor (G-CSF). This study found that the ectopic expression of AML1-MTG8 elevates the expression of the G-CSF receptor (G-CSFR). Analysis of the promoter region of the G-CSFR gene revealed that up-regulation of G-CSFR expression by AML1-MTG8 does not depend on the AML1-binding sequence, but on the C/EBP (CCAAT/enhancer binding protein) binding site. The results suggest that the overproduction of G-CSFR is at least partly mediated by C/EBPepsilon, whose expression is activated by AML1-MTG8. The ectopic expression of G-CSFR in L-G cells induced cell proliferation in response to G-CSF, but did not inhibit cell differentiation into mature neutrophils. Overexpression of C/EBPepsilon in L-G cells also stimulated G-CSF-dependent cell proliferation. High expression levels of G-CSFR were also found in the leukemic cells of AML patients with t(8;21). Therefore, G-CSF-dependent cell proliferation of myeloid precursor cells may be implicated in leukemogenesis.

Animals↗

PubMed1990

Receptor binding of human granulocyte colony-stimulating factor to the blast cells of myeloid leukemia.

Human granulocyte colony-stimulating factor (G-CSF) rapidly loses the biological activity and the receptor binding capacity following radioiodination. We have made a mutein of human G-CSF, KW-2228, in which Thr-1, Leu-3, Gly-4, Pro-5, and Cys-17 were respectively substituted with Ala, Thr, Tyr, Arg, and Ser; showed more potent G-CSF activity; and retained full biological activity and receptor binding capacity at least 2 weeks of radioiodination. G-CSF is an effective growth factor for the blasts of myeloid leukemia. Radioiodinated KW-2228 was prepared using solid-phase glucose oxidase-lactoperoxidase. Human leukemia cell lines and the blast cells from leukemia patients were examined for binding. High affinity binding sites were identified on myeloid cell lines and on the blasts obtained from acute myeloid leukemia patients. Scatchard analysis showed that a single binding site for G-CSF was observed (361-1688 receptors/cell; Kd 128-1400 pM). In contrast, specific binding of 125I-KW-2228 was not demonstrated on lymphoblastic cell lines or the blast cells of acute lymphoid leukemia or lymphoma. This difference was reflected in the effectiveness of G-CSF to stimulate colony formation in acute myeloid leukemia blasts, while G-CSF did not stimulate colony formation of the blast cells from acute lymphoid leukemia.

Blast Crisis↗

PubMed1994

Adhesiveness of granulocyte precursors in chronic granulocytic leukemia.

Adhesiveness of myeloblasts, promyelocytes, myelocytes, metamyelocytes, bands and polymorphonuclear neutrophils (PMN's) from the blood of patients with chronic granulocytic leukemia (CGL) was studied. The adhesiveness of the cells to the substrate (glass) was tested in the presence of protein under dynamic conditions, i.e. when the suspension of cells was flowing over the substrate. It was found that adhesiveness of the CGL granulocyte precursors increased with maturation except for the myeloblasts. They exhibited a greater adhesiveness than the more mature promyelocytes. Changes in the physical and chemical parameters of CGL granulocytes occurring during maturation are discusses in the aspect of their adhesiveness.

Cell Adhesion↗

PubMed1995

Separation of myeloid and erythroid progenitors based on expression of CD34 and c-kit.

In this report, a novel approach is described to physically separate erythroid progenitors from monocyte and granulocyte progenitors, based on the expression of CD34 and Kit. Using biotin-labeled human Kit ligand (KL) and flow cytometry, Kit was detectable on 2% to 3% of the nucleated cells in rhesus monkey bone marrow. Combination of biotin-KL with CD34 monoclonal antibodies (MoAb) showed that Kit was expressed on subsets of CD34low and CD34pos cells. Our data clearly demonstrate that CD34pos cells are more heterogeneous with respect to Kit expression than observed in studies using Kit MoAb. A small cluster, approximately 7% of the CD34pos cells, expressed CD34 at submaximal levels and stained brightly with biotinylated KL. This CD34pos/kithi fraction contained predominantly erythroid progenitors (burst-forming units-erythroid; BFU-E). The majority of the granulocytic and monocytic progenitors (colony-forming units-granulocyte/macrophage; CFU-GM) were CD34pos/kitmed. Some BFU-E were also detected in the CD34pos/kitmed and CD34low/kitpos fractions at low frequency. In the latter subset, most erythroid colony-forming units (CFU-E) were recovered. Using three-color flow cytometry, we analyzed expression of Kit in relation to that of CD34 and the class II major histocompatibility antigen, RhLA-DR. The most immature bone marrow cells that can be identified in vitro, ie, CD34pos/RhLA-DRlow cells, were kitmed. The CD34pos/kithi and CD34pos/kitneg subsets predominantly contained the more mature RhLA-DRbright cells. Our results demonstrate that erythroid precursors express c-kit at much higher levels than monomyeloid precursors and pluripotent progenitors. The difference in expression levels of CD34 and c-kit can be exploited to isolate BFU-E populations that are virtually devoid of nonerythroid cells.

Animals↗

PubMed1993

[Significance of sympathetic-adrenal structures in hematopoiesis regulation in cytostatic myelodepression].

The role of the sympathetic nervous system in the regulation of bone marrow hematopoiesis has been studied on mice CBA after administration of 5-fluorouracil (114 mg/kg). The double injection (3-5 minutes before and 5 hours after 5 + U) of ganglionic blocking drug (pentamine, 6 mg/kg), alpha-adrenergic (dihydroergotamine, 3.9 mg/kg) or beta-adrenergic antagonists (propranolol, 5 mg/kg) inhibited the post-cytostatic reparation of erythro- and granulocytopoiesis. Besides, addition of the same neurotropic antagonists and 5-FU (10(-7) M) to bone marrow culture led to 1.5-3 fold decrease of cell content in comparison with alone cytostatic after 24 hours incubation. On the contrary injection of neuroblocking agents (twice in 5 hours) on day 3 after 5-FU administration elevated the total count of erythroid cells immature and mature granulocytic leukocytes in bone marrow and polymorphonuclear leukocytes in blood. Thus, the unequal role of the sympathetic nervous system in the regulation of hematopoiesis at the different periods after high dose of 5-FU administration has been demonstrated.

Adrenal Glands↗

PubMed1990

Expression of leukocyte alkaline phosphatase gene in normal and leukemic cells: regulation of the transcript by granulocyte colony-stimulating factor.

The levels of leukocyte alkaline phosphatase (LAP) messenger RNA (mRNA) are evaluated in B and T lymphocytes, monocytes, and polymorphonuclear cells (PMNs), and this transcript is found to be present only in PMNs. Precursors of the myelomonocytic pathway, represented by leukemic cells isolated from several cases of chronic myelogenous leukemia (CML) in its stable and blastic phase and acute myelogenous leukemia (AML), are devoid of LAP transcript. These data support the notion that LAP is a marker of the granulocyte terminal differentiation. Despite the absence of LAP mRNA in both the myeloid and the lymphoid precursors, nuclear run-on experiments show constitutive transcription of the LAP gene in leukemic cells obtained from AML, CML, as well as acute lymphoblastic leukemia (ALL) and B-cell chronic lymphocytic leukemia (B-CLL). In CML and in chronic myelo-monocytic leukemia (CMML) PMNs, granulocyte colony-stimulating factor (G-CSF) specifically accumulates LAP mRNA without showing a substantial increase in the rate of transcription of the LAP gene. Once increased by G-CSF, LAP mRNA is very stable, showing a half-life of more than 4 hours in the presence of actinomycin-D. G-CSF is suggested to play a pivotal role in the modulation of LAP transcript in PMNs.

Alkaline Phosphatase↗

PubMed1999

Expression of granulocyte colony-stimulating factor- and granulocyte-macrophage colony-stimulating factor-associated signal transduction proteins of the JAK/STAT pathway in normal granulopoiesis and in blast cells of acute myelogenous leukemia.

Acute myelogenous leukemia (AML) is characterized by the malignant transformation of hematopoietic stem cells leading to dysregulated growth and differentiation of myeloid cells. Normally, proliferation and differentiation of myeloid cells are regulated by cytokines such as granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF). Abnormal signaling of the signal transduction pathway from the cytokine receptors via Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) might be involved in the pathogenesis of AML. We examined whether an abnormal expression of one of the four JAKs, STAT1, STAT3, STAT5, or the tyrosine phosphatase SHP-1, a negative regulator of this pathway, is associated with malignant transformation in AML. Analysis of the expression of proteins of the JAK/STAT pathway in normal myeloid cells at three stages of maturation revealed a strong expression of all proteins in CD34+ cells, whereas the level of the proteins was significantly lower in granulocytic precursors and mature neutrophils. Furthermore, during maturation the relation of the isoforms of STAT1 and STAT3 changed from predominantly alpha to predominantly beta. Leukemic blast cells from 25 patients and 12 cell lines showed a high level of STAT proteins and SHP-1, whereas a deficiency of at least one of the four JAKs was found in 10 of 25 patients. In primary AML blast cells a deficiency of three JAKs was more common in patients with an abnormal karyotype. In addition, a lack of JAK2 and Tyk2 protein was strongly associated with the FAB M2 phenotype. The proliferation rate in response to GM-CSF available in a small number of patients appears to be related to the JAK2 expression. Our data suggest that the degree of expression of G-CSF/GM-CSF receptor-associated proteins of the JAK/STAT pathway in normal myeloid cells is related with their clonogenic potential. STAT3 appears to be involved in early differentiation. Similar to CD34+ cells, it is likely that the high levels of STATs and SHP-1 found in leukemic cells reflects their proliferative activity, whereas a lack of members of the JAK family might lead to an inability to proliferate in response to G-CSF/GM-CSF described in a considerable percentage of AML blasts.

Antigens, CD34↗

PubMed1978

Cell kinetics and chemotherapy: a critical review.

The paper reviews methods of studying cell kinetics in man, cell population kinetics of human tumors and bone marrow, drug interactions and the cell cycle, and possible applications to chemotherapy. The conclusions drawn are: (1) Cell cycle time and S-phase duration for proliferating granulocyte precursors in human bone marrow are poorly defined but are probably shorter than median values for most human tumors, including leukemia. (2) Most drugs have greater toxicity for cycling cells and some variation in toxicity at different phases of the cell cycle. There is a special need for chemotherapy directed at slowly proliferating and hypoxic tumor cells. (3) Pretreatment indices of tumor cell kinetics are of little value in choosing drugs or in predicting response. (4) Experiments in animals have demonstrated that therapeutic index may depend on schedule. Knowledge of cell kinetics in animals rarely allows prediction of the optimal schedule and is unlikely to do so in man. Optimal schedules in mice are not directly relevant to man. (5) Measurement of tumor labeling index or DNA histogram by flow microfluorimetry to detect cell synchrony is of little benefit in scheduling if concurrent changes in bone marrow are ignored; these methods are invalid at short intervals after treatment because surviving clonogenic cells are indistinguishable from a larger number of drug-damaged cells prior to their lysis. (6) The major factor determining the outcome of chemotherapy is the availability of drugs with activity for the tumor and acceptable host toxicity. Claims that complex schedules using several drugs are effective because of synchrony or kinetic differences of tumor and normal tissue are at present unsubstantiated.

Animals↗

PubMed1997

Granulocyte colony-stimulating factor receptor at various differentiation stages of normal and leukemic hematopoietic cells.

Granulocyte colony-stimulating factor (G-CSF) is the most important cytokine in granulopoiesis, and induces the proliferation and differentiation of normal bone marrow granulocytic precursors. The physiologic effect of G-CSF is mediated through binding to specific cell surface receptors for G-CSF. Using a newly-devised quantitative flow-cytometric assay, we analyzed the expression of G-CSF receptors on normal and leukemic hematopoietic cells. In normal donors, G-CSF receptors are widely expressed from CD34-positive immature bone marrow cells to mature peripheral granulocytes. The highest expression of G-CSF receptors is observed in peripheral granulocytes. In the bone marrow, the level of G-CSF receptors expression increases in the following order; CD34+ CD33- cells < CD34+ CD33+ cells < CD34- CD33+ cells, indicating that G-CSF receptors are expressed on myeloid cells from a very early stage of differentiation and that the level of expression increases with the progress of cell maturation. G-CSF receptors are also detected on blast cells of patients with acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). The number of cell surface receptors varies from patient to patient, and no clear correlation is observed between the expression of receptors and the leukemia subtype or the cell surface markers. In this respect, the clinical use of G-CSF should be carefully controlled in ALL as well as AML patients.

Antigens, CD↗

PubMed2004

Functional expression of high-affinity receptor for immunoglobulin E on mast cells precedes that of tryptase during differentiation from human bone marrow-derived CD34 progenitors cultured in the presence of stem cell factor and interleukin-6.

BACKGROUND: CD34(+) progenitor cells develop into tryptase(+), CD117(+) mast cells when cultured in the presence of recombinant human stem cell factor (rhSCF). However, spontaneous IgE receptor (FcepsilonRI) expression during human mast cell development is not well examined. OBJECTIVE: Here, the expression and function of FcepsilonRI in and on human bone marrow-derived mast cells (HBMMCs) during development were investigated. METHODS AND RESULTS: At 4 weeks of culture, predominant cells expressed high-affinity IgE receptor alpha chain (FcepsilonRIalpha) on the cell surface determined by flow cytometry, but CD117 was less expressed. Immunocytochemistry with antitryptase mAb and anti-FcepsilonRIalpha mAb revealed intracellular and surface expression of FcepsilonRIalpha at 2 weeks of culture, but tryptase was less expressed. FcepsilonRIalpha mRNA transcript preceded that of tryptase mRNA at 2 weeks of culture determined by real-time RT-PCR, and FcepsilonRIalpha, FcepsilonRIbeta, FcepsilonRIgamma, and tryptase mRNA increased along with differentiation. FcepsilonRIalpha cross-link on HBMMC and 4-week-old mast cells/mast cell precursors induced the release of IL-5 and granulocyte macrophage-colony stimulating factor, which was enhanced by rhSCF. CONCLUSION: These data indicated that HBMMC constitutively and spontaneously expressed functional FcepsilonRI subunits at the early stage of differentiation, probably because of the differences in the ability and functional property of progenitors.

Antigens, CD34↗

PubMed1998

The IFN-inducible nucleoprotein IFI 16 is expressed in cells of the monocyte lineage, but is rapidly and markedly down-regulated in other myeloid precursor populations.

IFI 16 is an interferon-inducible nucleoprotein expressed by human monocytes. IFI 16 and a related mouse protein, p202, control cellular proliferation by binding and modulating the functions of cell cycle regulatory factors including p53 and the retinoblastoma gene product, pRb. In this study, we examined IFI 16 expression in myeloid precursor cells cultured in vitro in colony-forming assays using granulocyte (G-) and granulocyte-macrophage (GM-) colony-stimulating factor (CSF). IFI 16 was expressed in 100% of CD34+ cells isolated from human bone marrow. When the CD34+ cells were induced to differentiate, two sub-populations of cells were identified by two-color cytofluorography: the CD14+ (monocytoid) cells all expressed IFI 16, whereas the CD14- (polymorphonuclear precursor) cells did not. The strongest expression of IFI 16 was in the cells staining brightest for CD14, whereas depletion of CD14+ monocytoid cells from mixed monocytic/granulocytic cultures largely abolished IFI 16-stained cells. Furthermore, in eight independent colony-forming assays, the number of IFI 16+ cells correlated closely with the numbers of monocyte precursors identified morphologically (R2 = 0.99), but was unrelated to the numbers of myelocytes, promyelocytes, and metamyelocytes; nor was IFI 16 expressed by erythroid or eosinophil precursors. We conclude that IFI 16 is expressed in CD34+ and monocytoid daughter cells, but is rapidly and markedly down-regulated at the corresponding stages of polymorphonuclear and erythroid development. This differential expression of IFI 16 in myeloid precursor subpopulations and its perceived molecular properties are consistent with a possible role in regulating myelopoiesis.

Animals↗

PubMed1990

Comparative levels of CALLA/neutral endopeptidase on normal granulocytes, leukemic cells, and transfected COS-1 cells.

We discovered that the common acute lymphoblastic leukemia antigen, CALLA (CD10), was identical to human neutral endopeptidase 3.4.24.11 (NEP), a Zn-binding glycoprotein with an extracellular active site capable of hydrolyzing several biologically active peptides. In this study we compare the expression of CALLA/NEP in terms of antigenic density and enzymatic activity at the cell surface and of messenger RNA (mRNA) levels on granulocytes, leukemic cells, and CALLA-transfected COS-1 cells. Mature granulocytes, the only readily available source of normal human CALLA, express relatively low but constant levels of antigen, NEP activity (3.5 pmol/min/10(6) cells), and mRNA. The two major CALLA-mRNA species of 6.5 kb and 3.8 kb, observed to date in a variety of cells and tissues, were also found in four independent granulocyte preparations. With leukemia cell lines, a correlation was established between the density of CALLA antigen and the level of enzymatic activity (3.4 to 21.0 pmol/min/10(6) cells). This paper constitutes the first report of NEP activity on blast cells derived from patients with non-T acute lymphoblastic leukemia (ALL); the levels of activity were variable (1.5 to 35.9 pmol/min/10(6) cells for six cases) but correlated with the level of CALLA assessed by flow cytometry. Heterogeneous levels of expression of the CALLA-mRNA species were also observed in non-T ALL cases that correlated with the level of CALLA expression at the surface of these cells. Very high levels of NEP activity were achieved by transfecting COS-1 cells with pSV-CALLA; 20% of the transfected cells were CALLA+ and expressed 550 pmol/min/10(6) cells. Extracts prepared from COS-1 cells transfected with pSV-CALLA (carrying human NEP cDNA) and pSVENK19 (carrying rabbit NEP-cDNA), respectively, gave Michaelis constant (Km) values of 50 mumol/L and similar inhibition curves with thiorphan. Thus the recombinant proteins encoded by these two genes have similar enzymatic properties, confirming the high degree of their structural relatedness. The expression of high levels of CALLA/NEP on COS-1 cells should allow the use of this system to test the effects of specific mutations on activity and might lead to the understanding of the role of CALLA in the onset and/or progression of leukemia.

Animals↗

PubMed1991

Recombinant human stem cell factor enhances the formation of colonies by CD34+ and CD34+lin- cells, and the generation of colony-forming cell progeny from CD34+lin- cells cultured with interleukin-3, granulocyte colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor.

We tested the ability of recombinant human stem cell factor (SCF) to stimulate isolated marrow precursor cells to form colonies in semisolid media and to generate colony-forming cells (CFC) in liquid culture. SCF, in combination with interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or granulocyte colony-stimulating factor (G-CSF) caused CD34+ cells to form increased numbers of granulocyte-macrophage colonies (CFU-GM), and to form macroscopic erythroid burst-forming units (BFU-E) in the presence of IL-3, erythropoietin (Epo), and SCF. We tested isolated CD34+lin- cells, a minor subset of CD34+ cells that did not display antigens associated with lymphoid or myeloid lineages, and CD34+lin+ cells, which contain the vast majority of CFC, and found that the enhanced colony growth was most dramatic within the CD34+lin- population. CD34+lin- cells cultured in liquid medium containing SCF combined with IL-3, GM-CSF, or G-CSF gave rise to increased numbers of CFC. Maximal numbers of CFU-GM were generated from CD34+lin- cells after 7 to 21 days of culture, and required the presence of SCF from the initiation of liquid culture. The addition of SCF to IL-3 and/or G-CSF in cultures of single CD34+lin- cells resulted in increased numbers of CFC due to the proliferation of otherwise quiescent precursors and an increase in the numbers of CFC generated from individual precursors. These studies demonstrate the potent synergistic interaction between SCF and other hematopoietic growth factors on a highly immature population of CD34+lin- precursor cells.

Antigens, CD↗

PubMed1979

The effects of humoral factors on amplification of nonrecognizable erythrocytic and granulocytic precursors.

These studies were to evaluate the effects of humoral factors on amplification of nonrecognizable erythrocytic and granulocytic precursors by the in vivo plasma clot diffusion chamber and the in vitro plasma clot culture methods. Changes in the plasma erythropoietin levels in the reticulocyte concentration and hematocrits of irradiated and nonirradiated Long-Evans rats exposed to hypoxia were also determined. While erythropoietin plasma concentrations appeared to affect BFU-E and CFU-E growth, results suggest erythropoietin may not be the sole regulator of red cell production and that inhibitors of chalone-like mechanisms may be involved. Measurements made on granulocyte precursors treated with colony stimulating factor (CSF) containing L-cell-conditioned medium revealed granulocytic colonies and burst-like formations similar to those seen for erythrocytic growth. There is strong evidence suggesting that CSF is a regulator of granulopoiesis; however, it is not the sole regulator and it appears that inhibitors may play an in vivo role. Growth of colonies with cell numbers not a power of 2 implies either asymmetric mitosis due to loss of genetic information required for continuing division, or differences in concentrations of, or ability to recognize, inhibitory factors. These possibilities are examined in the light of results from in vivo and in vitro culture techniques.

Animals↗