SEARCH · PubMed Health

Results for “Granulocyte Precursor Cells”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 757 records · Page 42Linked to original sources

PubMedDate not supplied

Misonidazole enhances cyclophosphamide toxicity to bone marrow.

Normal bone marrow function was surveyed in animals that received cyclophosphamide after treatment with small, multiple doses of misonidazole. Peripheral blood white cell counts, cell differentials, hematocrits, bone marrow white cell counts and committed granulocyte-macrophage precursors (CFUc) were monitored for several days following treatment with misonidazole and cyclophosphamide. When results obtained from animals treated with physiological saline or misonidazole in advance of cyclophosphamide were compared, no significant differences were noted in routine assays of white blood cell count, cell morphology or hematocrit. Pre-treatment with misonidazole, however, caused a significant reduction in survival and delay in recovery of bone marrow CFUc (p less than .01). The combined use of misonidazole and cyclophosphamide also reduced animal survival (DMF = 1.2), with the majority of deaths being attributable to failure of normal hematopoietic function. These results suggest that misonidazole enhances the myelotoxicity associated with cyclophosphamide use. This additional damage is not detectable using routine hematological assays, but is demonstrable in assays of bone marrow stem cells and animal survival studies.

Animals↗

PubMed1998

Leukemic cells with 11q23 translocations express granulocyte colony-stimulating factor (G-CSF) receptor and their proliferation is stimulated with G-CSF.

We report a 20-month-old boy with acute lymphoblastic leukemia with the 11q23 translocation whose blasts markedly increased in peripheral blood after intravenous granulocyte colony-stimulating factor (G-CSF) administration, but disappeared after stopping G-CSF. The in vitro study showed that the leukemic cells separated from this patient expressed G-CSF receptor (G-CSFR) and an addition of G-CSF stimulated their proliferation by 3H-thymidine incorporation assay (stimulation index, 4.9). To clarify whether or not leukemic cells with 11q23 translocations generally express G-CSFR and show proliferative response to G-CSF, we performed the similar in vitro experiments using eight leukemic cell lines with 11q23 translocations. We found that all cell lines examined expressed G-CSFR (20-98%) and proliferation of seven leukemic cell lines was significantly enhanced in response to G-CSF (stimulation index >1.5 in five cell lines), suggesting a possible participation of the G-CSF/G-CSFR interaction in the process of growth regulation of leukemic cells with 11q23 translocations.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1980

Effect of daily administration of cytotoxic drugs on the erythroid and granulocytic repopulating ability of rat bone marrow.

The erythroid and granulocytic repopulating ability of rat bone marrow has been measured after daily administration of three alkylating agents: dimethylmyleran, busulphan and cyclophosphamide. Three different patterns of response were observed. The results emphasize the variability of the response of haemopoietic tissue to repeated administration of different cytotoxic drugs and provide further evidence that erythroid and granulocytic repopulating assays measure different populations of precursor cells.

Animals↗

PubMed1978

Immune suppression of hematopoiesis.

Recent evidence suggests that immune mechanisms can injure proliferating hematopoietic precursor cells in the bone marrow. These may involve either humoral antibody or cell-mediated cytotoxic mechanisms. Immune injury can result in a variety of bone marrow failure syndromes. Immunologically induced abnormalities or blood cell production may be restricted to a single series, such as erythrocyte or granulocyte precursors, or may involve several hematopoietic lines; clinical manifestations reflect the cell line or lines that are injured. Immune suppression of hematopoiesis has now been described in pure red cell aplasia, immune panleukopenia, systemic lupus erythematosus, atypical cases of aplastic anemia and miscellaneous other hematologic diseases.

Agranulocytosis↗

PubMed1987

Antibodies to granulocyte precursors in selective myeloid hypoplasia and other suspected autoimmune neutropenias: use of HL-60 cells as targets.

Patients with syndromes of autoantibody-mediated hematocytopenias may manifest signs of increased cell destruction and/or decreased cell production, depending on the maturity of the target cell and the effects of antibody binding. The purpose of this study was to use a cultured human cell line of hematopoietic origin for in vitro assays of antibody binding to overcome the relative inaccessibility of natural human marrow progenitor cells. This report describes the detection, using radioiodinated staphylococcal protein A (SPA), of antibodies binding to a human promyelocytic cell line (HL-60) in sera from three patients with chronic idiopathic granulocytic hypoplasia ("pure white cell aplasia," PWCA) and 22 patients with other syndromes of suspected immune neutropenia. Bone marrow from patients with increased IgG binding to HL-60 cells showed less than 15% granulocytic lineage cellularity in 11 of 17 cases. In vitro differentiation of HL-60 cells by retinoic acid resulted in increased IgG binding for sera that had shown increased IgG binding to mature granulocytes but not undifferentiated HL-60 cells; in contrast, for sera with antibodies to untreated HL-60 cells and for normal serum, in vitro differentiation had little effect on IgG binding. Antibodies eluted from mature granulocytes were similar to the parent serum regarding the ratio of IgG binding to mature cells v HL-60 cells. No sera from 19 patients with febrile transfusion reactions showed increased IgG binding to HL-60 cells in the absence of increased IgG binding to mature granulocytes, although two sera had antibodies to both cell types. The use of HL-60 cells as targets may permit measurement of serum antibodies associated with granulocytic hypoplasia. In combination with assays to detect antibody binding to mature granulocytes, these techniques may discriminate among autoantibody specificities for antigens that are gained, conserved, or lost during myeloid maturation.

Aged↗

PubMed1978

Separation of rabbit marrow precursor cells by combined isopycnic sedimentation and electronic cell sorting.

Separation of developing cells into fractions of differing stages of maturity is critical to effective biochemical study of the process of cellular differentiation. Density gradient techniques utilizing rate-zonal or isopycnic separations have permitted partial separations based on cell mass or cell density. In this study the separation of various rabbit marrow cells was improved by high-speed flow analysis and sorting in a Coulter Two-Parameter Cell Sorter. After preliminary isopycnic separation of marrow cells in Ficoll-Hypaque, cells were sorted into lymphoid and myeloid elements, utilizing light-scatter (LS) profiles to determine sorting. Characteristic LS patterns were present for erythrocytes, lymphocytes, devitalized cells, and granulocytes. When erythrocytes and their precursors were removed by hypotonic lysis, the remaining granulocytes could be sorted to give samples with much greater purity with respect to developmental stage than was possible with density gradients alone. Thus the combination of techniques represents a significant improvement in the ability to study the mechanisms of normal or altered cellular maturation.

Animals↗

PubMed1993

Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class II-negative progenitor in mouse bone marrow.

The developmental origin of dendritic cells, a specialized system of major histocompatibility complex (MHC) class II-rich antigen-presenting cells for T-cell immunity and tolerance, is not well characterized. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to stimulate dendritic cells, including growth and development from MHC class II-negative precursors in suspension cultures of mouse bone marrow. Here we studied colony formation in semi-solid methylcellulose cultures, a classical bioassay system in which GM-CSF induces the formation of mixed granulocyte-macrophage colonies. When colonies were induced from MHC class II-negative precursors, a small subset (1-2%) of typical dendritic cells developed alongside macrophages and granulocytes. The dendritic cells were distinguished by their cytologic features, high levels of MHC class II products, and distinct intracellular granule antigens. By using differential adherence to plastic, enriched populations of the various myeloid cell types were isolated from colonies. Only the dendritic cells stimulated a primary T-cell immune response, the mixed leukocyte reaction, and the potency was comparable to typical dendritic cells isolated from spleen. Macrophages from mixed or pure colonies were inactive as stimulator cells. Therefore, three distinct pathways of myeloid development--granulocytes, macrophages, and dendritic cells--can develop from a common MHC class II-negative progenitor under the aegis of GM-CSF.

Animals↗

PubMed2000

The 5-aminolaevulinic acid-based photodynamic effects on nuclei and nucleoli of HL-60 leukemic granulocytic precursors.

To provide more information on the 5-aminolaevulinic acid (ALA)-based photodynamic effect (PDE) on nuclei and nucleoli of individual leukemic cells, these structures were studied in cultured HL-60 cells which originated from leukemic highly immature and less differentiated precursors of granulocytes. The nuclear morphology was visualized by panoptic May-Grünwald/Giemsa staining and cytochemical method for DNA, nucleoli were visualized by cytochemical methods for the demonstration of RNA and silver stainable proteins including those of interphase silver stained nucleolus organizer regions (AgNORs). In most cells ALA-based photodynamic treatment (PDT) produced marked alterations such as formation of apoptotic bodies, and large condensation of nuclear chromatin structure but without nuclear segmentation. Such changes are in harmony with the apoptotic process induced in these cells but without previous terminal differentiation. In nucleoli ALA-based PDT produced the reduction and disappearance of nucleolar silver stainable particles (SSPs) representing AgNORs which apparently reflected the alteration of the nucleolar biosynthetic activity and cell proliferation. The latter is also reflected by the disappearance of mitotic divisions. On the other hand, a small subpopulation of cells was less sensitive or resistant to the ALA-based PDE since they did not show mentioned nuclear and nucleolar alterations.

Aminolevulinic Acid↗

PubMed1985

Differential expression of HLA-DR antigens in subsets of human CFU-GM.

Expression of HLA-DR surface antigens by granulocyte/monocyte colony-forming cells (CFU-GM) may be important in the regulation of proliferation of these cells. Using immunological techniques to enrich for progenitor cells, we investigated the expression of HLA-DR in subsets of CFU-GM. "Early" (day 14) CFU-GM express higher levels of HLA-DR than do "late" (day 7) CFU-GM. Among late CFU-GM, cells destined to form monocyte (alpha-naphthyl acetate esterase-positive) colonies express higher levels of HLA-DR than do CFU-GM destined to form granulocyte (chloroacetate esterase-positive) colonies. Because high-level expression of DR antigen was a marker for monocyte differentiation, we examined several lymphokines for their effects on both DR expression and in vitro commitment to monocyte differentiation by myeloid precursor cells. DR antigen density could be increased by more than twofold over 48 hours upon exposure to gamma-interferon (gamma-IFN), whereas colony-stimulating factors had no effect. This was associated with a dose-dependent inhibition of total CFU-GM number, and a relative, but not absolute, increase in the ratio of monocyte colonies to granulocyte colonies. Similarly, in day 7 suspension cultures of purified myeloid precursor cells, gamma-IFN inhibited cell proliferation and increased the ratio of monocytes to granulocytes. Thus, despite the induction of high levels of HLA-DR antigen on precursor cells (a marker of monocyte commitment), the dominant in vitro effect of gamma-IFN was inhibition of granulocyte differentiation.

Antibodies, Monoclonal↗

PubMed1985

Enrichment of myeloid progenitor cells from normal human bone marrow using an immune-rosette technique.

In this study we have developed methods for purification of myeloid progenitor cells (CFU-Cs) from normal human bone marrow cells. Bone marrow aspirates were obtained from volunteers, and mononuclear cells (MNCs) were separated by Ficoll-Hypaque gradient centrifugation. T- and B-lymphocytes, monocytes, mature granulocytes, and erythroid precursors were eliminated by an immune-rosette technique using a panel of murine monoclonal antibodies and immunoglobulin (Ig)-coated sheep red blood cells (SRBCs). MNCs were treated with OKT3, B1, M3, Mo5, and EP1 monoclonal antibodies, which are reactive with T cells, B cells, monocytes, granulocytes, and erythroid precursors, respectively. Antibody-treated MNCs were incubated with SRBCs that had been coated with goat antirabbit IgG F(ab')2 and rabbit antimouse Ig for immune rosetting. Rosetted cells were then separated from nonrosetted cells in Ficoll-Hypaque. Nonrosetted cells were, in the second step, treated with an OKIa1 monoclonal antibody and again separated into an Ia+ and Ia- cell fraction by the same manner; 39% +/- 19.2% (mean +/- 1 SD, range 16.3%-75.4%) of CFU-Cs (colonies plus clusters) were recovered in the OKT3-, B1-, M3-, Mo5-, EP1- cell fraction, and the number of CFU-Cs grown in semisolid agar was 149.6 +/- 73.0 (64.0-309.0)/10(4) plated cells in this purified fraction, representing an enrichment of 14.2 +/- 6.4 (6.0-27.3)-fold when compared with unseparated marrow cell fractions. CFU-Cs were enriched 17.7 +/- 8.6 (6.1-28.3)-fold in the Ia+ cell fraction. These purified myeloid precursors would be of value for in-depth studies of the interactions between hematopoietic progenitor cells and regulatory factors that influence their proliferation and differentiation and also of drug metabolism and determinants of cytotoxicity.

Adolescent↗

PubMed1992

Macrophage development: I. Rationale for using Griffonia simplicifolia isolectin B4 as a marker for the line.

The isolectin B4 of Griffonia simplicifolia (GSA I-B4) binds to cell membrane glycoconjugates bearing terminal alpha-D-galactose, which macrophages possess. We have investigated the merits of its use as a marker for cells of this lineage when examining the early origin of macrophage populations in rat embryos, the stages and time scale of transformation from precursor forms to active, matured cells, and the response of precursors and macrophages to colony-stimulating blood factors, the last two studies conducted in organ cultures of prenatal lungs. In the present instance, GSA I-B4 was used either coupled with fluorescein (FITC) for light microscopy of living and fixed cells, or with peroxidase for light or electron microscopy. Control incubations of lung culture-derived macrophages proved that staining resulted from specific binding to galactosyl units on the cell membrane, since it was competitively inhibited by alpha-D-galactose. The lectin binds to few cells in 14-day prenatal lung explants but to a great many macrophages that subsequently develop in the cultures, indicating that it can be relied on for quantitative studies on population growth; however, it is important to provide reagents with good access to the cells. Apart from macrophages and their precursors, virtually no cells in prenatal lung cultures bind this lectin. Granulocytes of adult blood are GSA positive, but they are not yet present in 14-day prenatal explants and do not develop subsequent to culturing; hence they are not a source of confusion for experimental studies using this system. Precursors of granulocytes begin to appear in rat embryos around day 13 and have GSA-positive cell membranes, but like definitive granulocytes they also have conspicuous peroxidase-positive lysosomal granules which serve to distinguish them from early macrophages, particularly when cells are studied at an ultrastructural level. With these objections cleared away, GSA I-B4 emerges as a valuable means to mark cells of the macrophage line, mature or immature.

Animals↗

PubMed1998

Neoplastic involvement of granulocytic lineage, not granulocytic-monocytic, monocytic, or erythrocytic lineage, in a patient with chronic neutrophilic leukemia.

Chronic neutrophilic leukemia (CNL) is a very rare myeloproliferative disorder. To determine the neoplastic origin of CNL, morphological and cytogenetical studies were made of colonies derived from hematopoietic progenitors of a patient with CNL. The patient's hematopoietic progenitors spontaneously formed colonies consisting of mature granulocytes, and cytogenetical study of the colonies indicated chromosome abnormalities identical to those in the patient's bone marrow cells. Analysis of colonies consisting of granulocytes and macrophages, macrophages, or erythrocytes disclosed a normal karyotype. These results demonstrated that the neoplastic process in this patient with CNL originated in hematopoietic progenitors capable of differentiating only into granulocytes, and not granulocytes and monocytes, monocytes, or erythrocytes.

Cell Lineage↗

PubMed1993

Selective prothymocyte targeting by prenatal diethylstilbesterol exposure.

Estrogens have been reported to modulate immunologic responses at both physiologic and pharmacologic concentrations. Treatment of experimental animals with the synthetic estrogen, diethylstilbesterol (DES), markedly decreases thymic cellularity, manifested histologically as a progressive loss of cortical thymic lymphocytes. In the present report thymic atrophy after prenatal DES exposure was found to be more severe than has been reported following adult exposure, indicating a possible greater sensitivity of the developing immune system to estrogenic hormones. DES exposure resulted in a limited alteration of cell maturation within the fetal thymus as evidenced by only slight alterations in the expression of CD4 and CD8 cell-surface antigens. To examine the possibility that DES targets hematopoietic stem cells in the fetal liver, cytometric analysis was conducted using a panel of fluorescent antibodies to quantitate the hematopoietic subpopulations present in control and DES-exposed Gestational Day (gd) 18 fetal mouse liver. There were no significant DES-induced alterations in the number of hematopoietic stem cells, or in fetal liver cells expressing CD44 (hematopoietic precursors), Mac-1 (granulocyte-macrophage lineage precursors), or CD45R (B-lineage lymphocytes) surface antigens. However, DES selectively reduced the number of fetal liver precursors containing the lymphocyte stem cell-specific DNA polymerase, terminal deoxynucleotidyl transferase, which suggested that DES may specifically target the fetal liver prothymocyte. Reconstitution of irradiated hosts with gd 18 fetal liver from vehicle and DES-exposed syngeneic donors demonstrated an impaired ability of the DES-treated fetal liver to repopulate the thymus of irradiated hosts. In addition, fetal liver cells enriched for prelymphoid cells contained potentially significant levels of estrogen specific receptors. Taken together these data, in conjunction with the lack of direct thymocyte injury (necrosis, apoptosis, and/or inhibition of cell proliferation) by DES treatment, suggest that estrogen-mediated thymic atrophy may result, at least in part, from a specific alteration in the lymphocyte stem cell population responsible for colonizing the thymus.

Animals↗

PubMed1995

Distinction between gamma c detection and function in YT lymphoid cells and in the granulocyte-macrophage colony-stimulating factor-responsive human myeloid cell line, Tf-1.

Peripheral blood monocytes respond to interleukin-2 (lL-2) and express the gamma common (gamma c) subunit of the lL-2 receptor (lL-2R) complex. However, the role of lL-2 in myeloid development has recently become of interest for several reasons, including the effect gamma c mutations may or may not have on myeloid development in patients with XSCID. Many studies of lL-2 function in the myeloid cell lineage have been performed on a murine background. To study gamma c expression and function in human myeloid precursors, we introduced the human myelomonocytic cell line, Tf-1, with a retroviral vector containing the human lL-2R beta subunit to create functional human intermediate lL-2R consisting of beta gamma c dimers. We have characterized this transfected variant of Tf-1 (Tf-1 beta) with regard to its response to lL-2. Unlike the parental Tf-1 cell line that is deficient in both lL-2R alpha and lL-2R beta expression, the Tf-1 beta transfectant binds and responds to lL-2 through intermediate-affinity lL-2Rs. Scatchard analyses indicate the number of intermediate-affinity receptors on Tf-1 beta is similar to the number found on the well-characterized YT cell line. However, detection of gamma c on Tf-1 beta cells is dramatically less than on YT cells by Western blot analysis and is undetectable by flow cytometric studies and surface iodinations. The gamma c component on YT cells is readily detected by all three methods. We conclude from these studies that the intermediate-affinity lL-2Rs on the Tf-1 cell line behave differently than those on YT cells with respect to gamma c detection. Either the gamma c molecule itself is different, or the cellular environment in which it functions is altered. Elucidation of gamma c function on this cell line will allow for its use as a model in which other cytokines using gamma c (including lL-2, lL-4, and lL-15) can be studied on the same cellular background.

Animals↗

PubMed2001

Development of dendritic cells in culture from human and murine thymic precursor cells.

The earliest T-precursor population in the adult murine thymus can give rise to dendritic cells (DC) in culture if stimulated with a cocktail of cytokines that includes interleukin (IL)-3, but not with cytokine mixes based on granulocyte-macrophage colony stimulating factor (GM-CSF), normally used to generate myeloid-derived DC. This and other evidence led to the proposal that two different lineages of DC exist, one lymphoid-related and the other myeloid-related. To determine whether this selective response to cytokines was restricted to murine DC, early human thymic T-precursors were isolated and their capacity to generate DC in response to various cytokines directly compared to their murine counterparts. In contrast to cultures of murine thymic precursors, CD34+CD1a- lineage marker negative (Lin-) precursor cells from the human thymus proliferated and generated DC with both the IL-3-containing cytokine mix lacking GM-CSF and with GM-CSF based cytokine mixes. These CD34+CD1a-Lin- human precursor cells also gave rise to NK cells under appropriate culture conditions, but produced no granulocyte, monocyte, eosinophil, megakaryocyte or erythroid cells in standard soft-agar colony-forming cell assays. Thus, although apparently lymphoid-restricted, the human thymic DC precursors responded to the myeloid factor GM-CSF as well as to the cytokines selective for murine lymphoid-related DC.

Animals↗

PubMed2001

Multilineage involvement in the 5q- syndrome: a fluorescent in situ hybridization study on bone marrow smears.

BACKGROUND AND OBJECTIVES: A pluripotent progenitor cell was demonstrated to be involved in myelodysplastic syndromes (MDS) with normal karyotype or with numerical chromosome aberrations, but the pattern of lineage involvement by the 5q31 deletion in the 5q- syndrome is unknown. We performed this study in order to define the distribution pattern of the 5q- anomaly better in the non-lymphoid cell compartment DESIGN AND METHODS: Bone marrow (BM) smears from 8 patients with the 5q- syndrome were studied by a modification of the fluorescent in situ hybridization (FISH) technique that allowed direct visualization of cell morphology. A commercial LSI EGR1 probe (Vysis Inc.) for the 5q31 band was used simultaneously in dual-color experiments with a chromosome-5-centromeric probe (Vysis Inc.) on BM smears from 8 patients with the 5q-syndrome. As additional internal controls a chromosome-7-centromeric probe and a 7q31 probe were used. To establish the sensitivity limit of this approach 5 normal BM smears were studied. All 8 patients had the 5q- chromosome as the sole anomaly in 45% to 75% of the interphase cells. RESULTS: For each patient 20-40 erythroblasts were analyzed: they were mostly proerythroblasts and basophilic erythroblasts. In all patients a clone carrying the 5q31 deletion was detected (35-50% of the cells, median 45%). Between 20-50 granulocyte precursors were scored; the 5q31 deletion was found in 40%-50% (median 45%) in all cases. The proportion of neutrophils carrying the 5q deletion was consistently lower than the corresponding value in promyelocytes (28.7% vs 45.6%). In the 20-25 megakaryocytes analyzable in all patients, the overall incidence of 5q31 deletion was 52-68%. Equal proportions of large multilobular megakaryocytes and hypolobular megakaryocytes characteristic of the 5q- syndrome were scored: the latter cells showed the 5q31 deletion more frequently than the former cells (93.6% vs 19.3% of the cells). In 66% to 100% of the cases (median 83%) a few cells with uncondensed nuclear chromatin pattern, and two or three prominent nucleoli with cytoplasmatic hypogranulation were seen in each sample carrying the 5q31 deletion. INTERPRETATION AND CONCLUSIONS: We arrived at the following conclusions: i) the transformation in the 5q- syndrome involves an early progenitor cell retaining the ability to proceed along multiple differentiation pathways; ii) there is a preferential distribution of the 5q31 deletion within immature cells and morphologically abnormal megakaryocytes.

Adolescent↗

PubMedDate not supplied

[Characteristics of the dynamics of hematopoietic precursor cells cloned in diffusion chambers and recorded in experiments on mice and dogs irradiated in median lethal doses].

In experiments with mice and dogs irradiated with LD50, it was shown the postirradiation depopulation of haemopoietic polypotent (CFUs) cell-precursors in mouse bone marrow was more pronounced than that of granulocytic and macrophagal cells (CFUdc). The rate of repopulation of CFUs during the first week was higher than that of CFUdc (T1/2 was 2.5 and 8.8 days respectively). In dogs, one could notice a partial change in the colony formation, a prolonged plateau period in the postirradiation CFUdc dynamics, and a coincidence in time with cellularity restoration in the bone marrow and peripheral blood leukocytes. It is suggested that in conditions of heterogeneous incubation in diffuse chambers, the haemopoietic cell-precursors are more mature than in the syngeneic system. The method of CFUdc determination has proved to be ineffective in estimating the onset and intensity of the postirradiation haemopoiesis recovery in dogs. The study of the bone marrow CFUdc population may, however, be used in intact animals to predict the probability of their death after irradiation within the median lethal dose range.

Animals↗

PubMed2003

[The effects of the Smad3-knockout on the hematopoiesis of mouse].

The effects of the Smad3- knockout on the hematopoiesis of mouse were investigated in this work. Five pairs of wild type and Smad3- null mice were studied. White blood cell(WBC), red blood cell(RBC) and platelet (PLT) counting of peripheral blood cells were performed with blood obtained from tails. And white blood cells were classified by their morphology. Bone marrow nucleated cells (BMNCs) were counted and classified. The CFU-GM, BFU-E, CFU-GEMM yields were measured in each pair of mice. CFU-S yield of each mouse was measured by injecting bone marrow cells into lethally irradiated 8-10 weeks old wild type female mice. And the pathomorphism of their bone marrows, spleens and livers were observed. As a result, WBC and PLT of Smad3- null mice were significantly higher than those in wild type mice. Smad3- null mice had much more proportion of granulocytes in classification. There wasn't any difference in RBC counting and BFU-E measurement. The yield of CFU-GM increased, while the yields of CFU-GEMM and CFU-S markedly reduced. Bone marrows are actively proliferative, with granulocytosis. The granulocyte/erythrocyte ratio increased. There were no obviously alterative in spleen and liver. Thus Smad3- knockout results in a decreased number of stem and progenitor cells. Moreover hematopoietic differentiation is abnormal with a tendency to forming more granulocytes and platelets. The effect of Smad3 on hematopoiesis is correlative to that of TGF-beta.

Animals↗