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Results for “Granulocyte Precursor Cells”

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PubMed1990

Bovine erythroid (CFU-E, BFU-E) and granulocyte-macrophage colony formation in culture.

Progenitor cells of bovine erythrocytes, megakaryocytes, and granulocyte-macrophages were cultured in agar or methylcellulose media. Colony formation was supported by cell-free conditioned medium from short-term cultures of concanavalin A-stimulated bovine peripheral blood leukocytes. Granulocyte-macrophage progenitors proliferated well in both types of semisolid culture media, giving rise to neutrophils (from granulocyte colony-forming units, CFU-G), eosinophils (from eosinophil CFU, CFU-Eo), monocyte-macrophages (from macrophage CFU, CFU-M), and mixed granulocyte-macrophages (from granulocyte-macrophage CFU, CFU-GM). Better growth of megakaryocytes, as well as late (erythroid CFU, CFU-E) and early (erythroid burst-forming units, BFU-E) erythroid progenitors was obtained with methylcellulose. Despite considerable variation in the numbers and types of colonies formed from different aspirates of bovine marrow, the numbers observed were generally comparable to those obtained from human and mouse bone marrow cells. The proliferation of bovine BFU-E and eosinophil progenitors herein described is the first successful report of the culture of these cell types.

Animals↗

PubMed1991

Uteroferrin: a progesterone-induced hematopoietic growth factor of uterine origin.

Uteroferrin is a purple progesterone-induced glycoprotein containing two molecules of iron per 35,000 molecular weight polypeptide, which has high amino acid sequence homology with Type 5 acid phosphatases from normal human placentae, from sera of patients with hairy cell leukemia, Gaucher's disease, and osteoporosis, as well as from normal spleens of pigs, cattle, rats, and mice. Results of the present study indicate that uteroferrin also has colony-forming unit (CFU) activity for committed erythroid (BFU-E) and granulocyte-monocyte/macrophage (CFU-GM) cell lines and exists as far back as the granulocyte, erythrocyte, monocyte/macrophage, megakaryocyte (CFU-GEMM) committed lineage. Uteroferrin exerts maximum CFU activities at 1 microgram/ml in serum-free culture medium with no supplemental iron (90 micrograms/ml ferric iron). However, when ferric iron concentration in medium was increased to 200 micrograms/ml, uteroferrin had maximum CFU activities at 100 pg/ml. Preincubation of uteroferrin with polyclonal antiserum or monoclonal antibody to uteroferrin effectively eliminated its CFU activities. Uteroferrin derived from human term placentae also exhibits BFU-E, CFU-GM, and CFU-GEMM activities. The mechanism by which uteroferrin stimulates proliferation and differentiation of primitive hematopoietic stem cells is unclear.

Acid Phosphatase↗

PubMed1990

Migration of stem cells and progenitors between marrow and spleen following thiamphenicol treatment of mice.

Recovery of hemopoiesis was studied after a 3-day treatment with the antibiotic thiamphenicol (TAP). A contrasting behavior of the spleen colony-forming units (CFU-S), granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst-forming units (BFU-E), and erythroid colony-forming units (CFU-E) numbers in the bone marrow versus those in the spleen was found. Whereas the cell numbers reached nadirs in the marrow, they peaked 30 to 100-fold above control values in the spleen on day 4. Simultaneously the number of CFU-S, BFU-E, and CFU-GM, but not of CFU-E, increased drastically in the peripheral blood. The tritiated thymidine kill of the splenic CFU-S was too small to explain the endogenous splenic production of these cells. A quantitative analysis further revealed that an effective erythropoiesis was established in the spleen. As a consequence, the first part of a reticulocytosis was mainly due to the splenic contribution, whereas the second part predominantly originated from a delayed marrow erythropoiesis. In contrast, the CFU-GM of the spleen did not effectively differentiate into granuloid precursors. The bulk of the granuloid production occurred in the marrow. The best explanation for these results is a net migration of CFU-S, BFU-E, and CFU-GM from the marrow to the spleen during early recovery, and a back-migration of CFU-GM to the marrow later in the recovery phase. These observations indicate a link between migration of hemopoietic cells and their differentiation at the two hemopoietic sites.

Animals↗

PubMed1994

Cytokine release by human bone marrow cells: analysis at the single cell level.

Regulation of haemopoiesis is closely mediated by a number of growth factors in the marrow microenvironment. The identification of the cell type secreting these regulatory polypeptides is difficult due to the heterogeneity of bone marrow cells. To analyse the release of haemopoietic growth factors by normal human bone marrow cells at the single cell level, we employed the reverse haemolytic plaque assay (RHPA). Freshly isolated human marrow cells were examined for the release of interleukin-1 alpha (IL-1 alpha), IL-3, IL-6 and granulocyte-monocyte colony stimulating factor (GM-CSF). In order to identify various cytokine-secreting cell types, the RHPA was combined with immunocytochemical or enzymatic staining. The total of secreting marrow cells as well as the amount of several secretory haemopoietic subpopulations could be determined with this technique under various conditions. Following incubation with pure serum-free medium without addition of any mediator, only few cells secreting either IL-1 alpha, IL-3, IL-6 or GM-CSF could be observed. After 2 h incubation with recombinant human-IL-1 alpha (rhIL-1 alpha) (10.0 ng/ml) or rhGM-CSF (10.0 pg/ml) the number of cytokine-secreting cells significantly increased for all secretory products tested. Using cytochemical staining reactions, we were able to identify 55% of all cells secreting a specific cytokine. Glycophorin C-positive erythropoietic cells turned out to be the largest fraction (up to 89%) of cytokine-releasing haemopoietic cells, followed by neutrophil granulocytes (between 6 and 48%), and monocytes/macrophages (between 4 and 23%). Only few CD 61-positive cytokine-secreting megakaryocytes could be detected. Dose- and time-dependent kinetics after stimulation with rhGM-CSF revealed that the bulk of secretory activity originates from haemopoietic or rather from erythropoietic cells following low level stimulation and after short stimulation time. Thus, our data are in keeping with the assumption, that especially erythropoietic cells are producing a repertoire of cytokines that is thought to exhibit regulatory functions within marrow microenvironment. In the present study the RHPA is presented as an appropriate tool for measuring cytokine release not only of cells of the haematopoietic system but also of other tissues, for example solid tumours or malignant lymphomas.

Bone Marrow↗

PubMed2002

Hematopoietic reconstitution of irradiated, stem cell-injected mice: early dynamics of restoration of the cell lineages of the spleen and bone marrow.

Hematopoietic stem cells, numbering approximately 1/100,000 cells in mammalian bone marrow, are capable of complete hematopoietic and immune reconstitution upon injection into a myeloablated host. The present study aimed to analyze the earliest events in reconstitution of lethally irradiated, host murine bone marrow and spleen, after injecting purified Thy 1(lo)Lin(-)Sca-1(+) stem cells. Thy-1(lo)Lin(-)Sca-1(+) cells were isolated by fluorescence-activated cell sorting (FACS) from the bone marrow of 4-week-old C57BL(Thy1.1, Ly5.1) mice and injected into preirradiated, syngeneic hosts. These stem cells were also injected into congenic hosts, i.e., C57BL(Thy1.2, Ly5.2), and confirmed the donor origin of hematopoietic cells in the reconstituted host mice. Hematologically stained smears of the spleen and bone marrow of stem cell-injected recipients were prepared at 11, 14, 17, 21, 24, and 28 days after stem cell injection, and nucleated erythroid cells, mature granulocytes, and their myeloid precursors, monocytes, and large and small lymphocytes were recorded as a proportion of all nucleated cells in each organ at each time interval. The results indicated that in the earliest post stem cell injection intervals, both organs were predominantly erythroid and myeloid. Only at the later intervals did both organs show high proportions of large lymphoid cells and their progeny, small lymphocytes. Thus, early (<1 month) dynamics of hematopoietic reconstitution after transplantation of purified hematopoietic stem cells, is cell lineage specific.

Animals↗

PubMed2000

Hemopoiesis in healthy old people and centenarians: well-maintained responsiveness of CD34+ cells to hemopoietic growth factors and remodeling of cytokine network.

In vitro hemopoiesis and hemopoietic cytokines production were evaluated in 9 centenarians (median age 100.5 years, age range: 100-104 years), 10 old people (median age: 71 years, age range: 66-73 years), and 10 young people (median age: 35 years, age range: 30-45 years), all carefully selected for their healthy status. The main findings were the following: (i) a trend towards a decreased absolute number of CD34+ progenitor cells in the peripheral blood of old people and centenarians, in comparison to young subjects; (ii) a well-preserved capability of CD34+ cells from old people and centenarians to respond to hemopoietic cytokines, and to form erythroid (BFU-E), granulocyte-macrophagic (CFU-GM), and mixed colonies (CFU-GEMM) in a way (number, size, and morphology) indistinguishable from that of young subjects; (iii) an age-related decreased in vitro production of granulocyte-macrophagic colony-stimulating factor (GM-CSF) and a decreased production of interleukin-3 (IL-3) in centenarians by phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC); (iv) a linear increase of the serum level of stem cell factor (SCF), measured in the above-mentioned subjects and in 65 additional subjects, including 4 centenarians. These data suggest that basal hematopoietic potential is well preserved in healthy centenarians, and that the hemopoietic cytokine network undergoes a complex remodeling with age.

Adult↗

PubMed1990

Different haematopoietic growth factors have different capacity in overcoming the in vitro interferon gamma-induced suppression of bone marrow progenitor cells.

Interferon gamma (IFN gamma) inhibits haematopoiesis in vitro and an in vivo role in bone marrow suppression has been implied from clinical studies. We investigated the capacity of three recombinant (r), human (h), haematopoietic growth factors to overcome the in vitro IFN gamma inhibition of bone marrow progenitor cells in a methylcellulose culture system. Granulocyte macrophage-colony stimulating factor (GM-CSF) partially reversed IFN gamma-induced suppression of granulocyte-macrophage colony formation, by increasing colony forming units-granulocyte macrophage (CFU-GM) in a proportion ranging from 54-101%. Interleukin-3 (IL-3) and granulocyte-colony stimulating factor (G-CSF) were much less effective. For erythropoiesis, IL-3 was much more effective and partially reversed IFN gamma-mediated inhibition by increasing burst forming units-erythroid (BFU-E) in a proportion ranging from 52-138%. GM-CSF and G-CSF had no significant effect on IFN gamma-induced suppression of BFU-E. In conclusion, haematopoietic growth factors have different capacity to overcome IFN gamma-induced suppression of marrow progenitor cells in vitro. The findings may have therapeutic implications, as combinations of growth factors may be more effective in treating bone marrow failure syndromes.

Bone Marrow Cells↗

PubMed1993

In vivo effects of recombinant interleukin-11 on myelopoiesis in mice.

Purified recombinant human interleukin-11 (rhuIL-11) was assessed for its in vivo effects on the proliferation and differentiation of hematopoietic progenitors as well as its capacity to accelerate the recovery of a drug-suppressed hematopoietic system. Dosage and time sequence studies demonstrated that administration of IL-11 to normal mice resulted in increases in absolute numbers of femoral marrow and splenic myeloid (granulocyte-macrophage colony-forming unit [CFU-GM], burst-forming unit-erythroid [BFU-E], CFU-granulocyte, erythroid, macrophage, megakaryocyte) progenitor cells and in stimulation of these progenitors to a higher cell cycling rate. This was associated with increased numbers of circulating neutrophils. Administration of IL-11 to mice pretreated with cyclophosphamide decreased the time required to regain normal levels of neutrophil and platelet counts in peripheral blood. In addition, IL-11 accelerated reconstitution to normal range of myeloid progenitors from bone marrow and spleen of myelosuppressed mice. These data suggest that IL-11 may play an important role in the regulation of hematopoiesis, and the application of this novel cytokine may have clinical therapeutic benefits.

Animals↗

PubMed1992

Effect of peripheral-blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy.

The haemopoietic growth factor granulocyte colony-stimulating factor (G-CSF; filgrastim) substantially shortens the period of severe neutropenia that follows high-dose chemotherapy and autologous bone-marrow infusion by stimulating granulopoiesis. Filgrastim also increases numbers of circulating progenitor cells. We have studied the ability of filgrastim to mobilise peripheral-blood progenitor cells and assessed their efficacy when infused after chemotherapy on recovery of neutrophil and platelet counts. 17 patients with non-myeloid malignant disorders received filgrastim (12 micrograms/kg daily for 6 days) by continuous subcutaneous infusion. Numbers of granulocyte-macrophage progenitors in peripheral blood increased a median of 58-fold over pretreatment values, and numbers of erythroid progenitors increased a median of 24-fold. Three leucapheresis procedures collected a mean total of 33 (SEM 5.7) x 10(4) granulocyte-macrophage progenitors per kg body weight. After high-dose chemotherapy in 14 of the patients (busulphan and cyclophosphamide), these cells were used to augment autologous bone-marrow rescue and post-transplant filgrastim treatment. Platelet recovery was significantly faster in these patients than in controls who received the same treatment apart from the infusion of peripheral-blood progenitors; the platelet count reached 50 x 10(9)/l a median of 15 days after infusion of haemopoietic cells in the study patients compared with 39 days in controls (p = 0.0006). The accelerated neutrophil recovery associated with filgrastim treatment after chemotherapy was maintained. This method may be widely applicable to aid both neutrophil and platelet recovery after high-dose chemotherapy; it will allow investigation of peripheral-blood progenitor-cell allotransplantation.

Adolescent↗

PubMed1994

Selection and characterization of early hematopoietic progenitors using an anti-CD71/S06 immunotoxin.

Most recently reported methods to select early hematopoietic cells basically rely on the depletion of committed progenitors. This task is generally accomplished by laborious procedures, which are sometimes difficult to reproduce. To simplify the selection method, we took advantage of the expression of the transferrin receptor (CD71) by proliferating committed progenitors and the lack of CD71 on noncycling immature progenitors. A monoclonal antibody (MAB) reactive with CD71 has been conjugated to the Saponaria officinalis seed ribosome-inactivating protein (SO6). The immunotoxin (IT) complex was used at increasing concentrations on normal non-phagocytizing bone marrow cells. A complete and reproducible killing effect on myeloid (colony-forming unit-granulocyte/macrophage [CFU-GM]) and erythroid (burst-forming unit-erythroid [BFU-E]) progenitors was observed for IT concentrations of 1 x 10(-7) M. Unconjugated SO6 or anti-CD71 MAB had no effect on cell growth and viability. IT-resistant cells were able to generate CFU-GM after 7, 14, and 21 days of suspension culture in the presence of 5637 CM. Maximal CFU-GM values were obtained at day 21 and nearly approached the pretreatment values (mean 2587 vs. 3877 CFU-GM/mL). Growth factor enhancement of CFU-GM yield was obtained only by stem cell factor (SCF) at day 7; SCF, as well as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3), had an enhancing effect at days 14 and 21. IT toxicity on highly immature progenitors was ruled out by evaluating the growth of long-term culture-initiating cells (LTC-IC) from IT-treated cultures. LTC-IC frequency was found to be 1 out of 1506 seeded cells, which is within the range of normal untreated BM cells. In conclusion, anti-CD71 IT allows a simple and complete depletion of committed progenitors while sparing immature hematopoietic cells. The high CD71 expression by leukemic cells makes the procedure potentially suitable for in vitro purging.

Antibodies, Monoclonal↗

PubMedDate not supplied

Identification of the human analogue of a regulator that induces differentiation in murine leukaemic cells.

We have recently purified murine granulocyte colony-stimulating factor (G-CSF), a regulatory glycoprotein which stimulates granulocyte colony formation from committed murine precursor cells in semi-solid agar cultures. G-CSF is one of a family of colony-stimulating factors that regulate the growth and differentiation of granulocytes and macrophages. While the other murine CSFs (granulocyte-macrophage (GM)-CSF, macrophage (M)-CSF and multi-CSF) show little or no differentiation-inducing activity on murine myelomonocytic leukaemia cell lines, G-CSF (or MGI-2(6)) is able to induce the production of terminally differentiated cells from WEHI-3B and other myeloid leukaemia cell lines. More importantly, G-CSF-containing materials suppress the self-renewal of myeloid leukaemia stem cells in vitro and the leukaemogenicity of treated myeloid leukaemic cells in vivo. It is important to identify the human analogue of murine G-CSF so that its effectiveness on human myeloid leukaemia cells can be assessed. Here we show that an analogue of G-CSF does exist among the CSFs produced by human cells and that the murine and human molecules show almost complete biological and receptor-binding cross-reactivities to normal and leukaemic murine or human cells. The human G-CSF analogue is identified as a species of CSF that we have previously described as CSF-beta.

Animals↗

PubMed1992

In vivo effect of interleukin-1 alpha on hematopoiesis: role of colony-stimulating factor receptor modulation.

To determine the mechanism(s) by which interleukin-1 (IL-1) promotes granulopoiesis in vivo, we examined the effect of in vivo administration of IL-1 alpha on colony-stimulating factor (CSF) receptor expression on bone marrow cells (BMCs) and whether this directly correlated with progenitor cell responsiveness. Administration of IL-1 alpha to mice induced the upregulation of both granulocyte-macrophage-CSF (GM-CSF) and IL-3 receptors, which reached a maximum 24 hours after IL-1 alpha injection on unfractionated BMCs. This upregulation was more pronounced on the progenitor-enriched cell population (lineage-negative [Lin(-)]). The enhanced GM-CSF and IL-3 receptor expression directly correlated with enhanced IL-3- or GM-CSF-induced growth of colony-forming unit-culture (CFU-c) or CFU-mixture (CFU-Mix; colonies containing macrophages, granulocytes, and erythroid cells). In addition, the absolute number of high proliferative potential-colony-forming cells (HPP-CFC) was increased fivefold. In contrast, granulocyte-CSF (G-CSF)-specific binding on unfractionated BMCs was rapidly (4 hours) reduced after IL-1 alpha administration and returned to control levels by 24 hours. This reduction correlated with IL-1 alpha-induced margination of mature granulocytes (RBC-8C5hi cells), which express high levels of G-CSF receptors. IL-1 alpha treatment did not affect G-CSF receptor expression on Lin- cells. Pretreatment of mice with anti-type I IL-1 receptor antibody blocked the IL-1 alpha-induced upregulation of GM-CSF and IL-3 receptor expression on BMCs. Taken together, as one possible mechanism, IL-1 alpha in vivo may stimulate the expression of functional GM-CSF and IL-3 receptors on BMCs indirectly, and, in concert with the induction of circulating CSF levels, may account for the ability of IL-1 alpha to stimulate hematopoiesis in vivo.

Animals↗

PubMed1994

Enhancing effects of cyclosporin A on hematopoietic progenitors: possible role of CD8+ T cells as negative regulators.

To elucidate the mechanism by which the administration of cyclosporin A (Cy A) improves a certain type of anemia, Cy A was orally administered to normal mice; hematopoietic activity, natural killer (NK) cell activity, and natural suppressor (NS) cell activity in the bone marrow (BM) were then examined. Hematopoietic colony formation was significantly enhanced by both 7-day and 21-day treatment with Cy A. Cy A did not, however, affect the total cell count or the numbers of macrophages, granulocytes, or B cells in the BM. Neither did Cy A affect the in vitro colony formation of the purified hematopoietic progenitors. These results suggest that Cy A acts on the negative regulators such as NK cells, NS cells, and CD8+ T cells. Since both NK and NS activity were also enhanced by Cy A treatment, these cells were not candidates. CD4+ or CD8+ T cells in the thymus, peripheral blood (PBL), and BM decreased as a result of the treatment. Therefore, to further examine the involvement of CD4+ or CD8+ T cells, hematopoietic colony formation was evaluated using bone marrow cells (BMCs) from mice purged of CD4+ and/or CD8+ cells. A significant enhancement of erythroid and multipotent colonies was observed in the BM of the CD8+ cell-purged mice. On the other hand, a significant enhancement of myeloid colonies was found in the BM of the CD4+ cell-purged mice. These findings suggest that single-positive T cells (particularly CD8+ T cells), which are diminished in number after Cy A treatment, are involved in the negative regulation of hematopoiesis.

Animals↗

PubMed2000

Differential expression of bcl-2 homologs in human CD34(+) hematopoietic progenitor cells induced to differentiate into erythroid or granulocytic cells.

The Bcl-2 family of proteins has been shown to play a central role in the regulation of apoptosis. We have examined the expression of several Bcl-2 homologs upon stimulation of CD34(+) human hematopoietic progenitor cells. CD34(+) cells were induced to differentiate into predominantly erythroid cells in the presence of erythropoietin (Epo) and stem cell factor (SCF), while the addition of G-CSF and SCF led to differentiation predominantly into granulocytic cells, as demonstrated by immunophenotyping and morphological examination of cultured cells. In Epo- and SCF-stimulated cells, we found a marked increase in the level of Bcl-x(L) protein expression and downregulation of Bax expression, apparent from day 4 and more pronounced on days 8 and 21. In contrast, Bcl-x(L) protein expression was downregulated in G-CSF- and SCF-stimulated cells compared with cells cultured in medium alone, whereas there was no sign of change in the level of Bax. Mcl-1 expression showed a biphasic expression pattern in both early erythropoiesis and early granulopoiesis, but with an inverse regulation. Thus, Mcl-1 levels initially decreased in granulocytic progenitor cells and increased in erythroid progenitor cells. Finally, Bcl-2 expression was significantly downregulated in both Epo and SCF and G-CSF- and SCF-stimulated cells. The role of the distinct upregulation of Bcl-x(L) in early erythroid differentiation was further examined by use of specific ribozymes against Bcl-x(L). Addition of Bcl-x(L) ribozymes promoted a clear increase in cell death of Epo- and SCF-stimulated cells, while erythroid differentiation was not affected. In conclusion, we found a distinct regulation of several Bcl-2 family members in CD34(+) cells dependent on the cytokine stimulation given. The use of Bcl-x(L)-specific ribozymes suggested that Bcl-x(L) is important for survival but not for differentiation of erythroid progenitor cells.

Adult↗

PubMed1990

Three quantitative assays for human erythroid burst-promoting activity of recombinant growth factors and of omentum-conditioned medium.

Human erythroid burst-promoting activity (BPA) of recombinant growth factors and crude materials, of media conditioned by omentum tissue (OMCM), and of media conditioned by the bladder carcinoma cell line (HTB9CM) was measured by three different culture methods. Using the two-stage culture method, significant activity was shown in OMCM (137%-329% of the control), HTB9CM (102%-333%), recombinant human (rh) granulocyte-macrophage colony-stimulating factor (rhGM-CSF) (179%-220%), rh interleukin 3 (rhIL-3) (232%-676%), and rh insulin-like growth factor 1 (rh IGF-1) (106%-175%), whereas there was no significant increase in the number of erythroid bursts by the same additives when the one-stage culture or the delayed erythropoietin method was employed. Linear dose-response curves were observed in the tested range of rhIL-3 and rhGM-CSF. We also observed that 1) a larger amount of rhGM-CSF was required for the optimal stimulation of erythroid burst-forming units (BFU-E) than for the optimal stimulation of granulocyte-macrophage colony-forming units (CFU-GM), and 2) even the maximum dose of rhGM-CSF increased erythroid bursts to a lesser extent than was possible by the addition of rhIL-3. The former results implies that BPA is not the major activity of GM-CSF, and the latter result, although it is not conclusive, suggests that the GM-CSF-responsive BFU-E represent only a subset population of BFU-E responsive to IL-3. The two-stage culture is a useful assay method for screening BPA in biological materials with respect to accuracy, dose responsiveness, and reproducibility.

Carcinoma↗

PubMed1999

Retinoic acid induces apoptosis of human CD34+ hematopoietic progenitor cells: involvement of retinoic acid receptors and retinoid X receptors depends on lineage commitment of the hematopoietic progenitor cells.

Retinoids are bifunctional regulators of growth and differentiation of hematopoietic cells. In this study we explored the effects of retinoic acid (RA) on apoptosis of human CD34+ hematopoietic progenitor cells isolated from normal bone marrow. RA (100 nM) induced an increase in the percentage of dead cells from 24% to 44% at day 6 (p < 0.05, n = 6) as compared to control cells cultured in medium alone. The effect was dose dependent and appeared relatively late. Significant differences were observed from day 4 onward. Apoptosis, or programmed cell death, was demonstrated as the mode of cell death by using the TUNEL assay, which detects single strand nicks in DNA, or by the Nicoletti technique demonstrating a subdiploid population by DNA staining. RA previously was found to inhibit granulocyte colony-stimulating factor--and not granulocyte-macrophage colony-stimulating factor--stimulated proliferation of CD34+ cells. However, we found that RA opposed anti-apoptotic effects of G-CSF and GM-CSF on CD34+ cells (G-CSF: 8% dead cells at day 6; G-CSF + RA: 20%; GM-CSF: 12%; GM-CSF + RA: 27%). Moreover, RA induced apoptosis of CD34+ cells and CD34+CD71+ cells stimulated with erythropoietin. To explore the receptor signaling pathways involved in RA-induced apoptosis, we used selective ligands for retinoic acid receptors (RARs; RO13-7410) and retinoid X receptors (RXRs; RO 25-6603). We found that RARs were involved in RA-mediated apoptosis of myeloid progenitor cells, whereas RARs as well as RXRs were involved in RA-mediated apoptosis of erythroid progenitor cells.

Antigens, CD34↗

PubMed1993

Residual myelotoxicity of lindane in mice.

Lindane (gamma-1,2,3,4,5,6-hexachlorocyclohexane), a widely used insecticide, may be found at low concentrations in the human diet. Male B6C3F1 mice given lindane daily at doses of 20 and 40 mg/kg body wt by gavage in corn oil for 3 days had suppressed bone marrow cellularity, erythrocyte precursors, granulocyte-macrophage progenitor cells (CFU-GM), and residual progenitor cell damage, which could be demonstrated by two whole-body irradiations (WBI) at 200 rads. Lindane exposure for 10 consecutive days at doses of 0, 10, or 20 mg/kg did not cause clinical abnormality or changes in body weights, but there were dose-dependent decreases in marrow cellularity, in more pluripotent stem cells and in committed CFU-GMs, which returned to control values by 4 weeks. These mice were then subjected to two 100-rad exposures of WBI at 4 and 9 weeks following cessation of lindane treatment. This level of irradiation caused only a transient drop in number of marrow progenitor cells. Control and lindane-exposed mice were examined at 1 and 6 weeks following the last irradiation, which was 10 and 15 weeks following the final lindane exposure. The lindane-exposed mice had lower progenitor cell numbers and slower recovery from the irradiation. These results indicate that lindane has significant myelotoxicity in mice and short-term lindane exposure can induce residual progenitor cell damage that can be demonstrated by subsequent irradiation.

Animals↗

PubMed1991

Age-related changes in various hemopoietic progenitor cells in senescence-accelerated (SAM-P) mice.

The effect of aging process on the hemopoietic system in senescence-accelerated (SAM-P) mice with respect to numbers of hemopoietic progenitor cells was investigated. The numbers of femoral granulocyte-macrophage colony-forming cells (CFU-GM), mast cell progenitors (mast colony-forming units, CFU-Mast), erythroid burst-forming units (BFU-E), and erythroid colony-forming units (CFU-E) in old mice (30-35 weeks old) decreased to 96%, 81%, 83%, and 87% of those of young mice (8-12 weeks old), respectively. The numbers of femoral fibroblast colony-forming cells (CFU-F) in old mice increased to 315% of those of young mice. The numbers of splenic CFU-GM, CFU-Mast, BFU-E, and CFU-E in old mice decreased to 7%, 43%, 25%, and 40% of those of young mice, respectively. In contrast, significant changes in these progenitor cells were not observed in the bone marrow. These findings suggest that the effect of the aging process on hemopoietic tissues in SAM-P mice is predominantly in the spleen.

Aging↗