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T Olofsson

Publications and source records attributed to T Olofsson.

At least 19 recordsLinked to original sources
PubMed1992

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) secretion by adherent monocytes measured by quantitative immunoassays.

The kinetics of GM-CSF and G-CSF secretion by purified adherent human monocytes were studied by quantitative immunoassays. Interleukin-1 (IL-1); 4-40 ng/ml and E. coli lipopolysaccharide (LPS); 0.1-1.00 ng/ml, were the most effective stimuli and induced dose-dependent secretion of both GM-CSF and G-CSF. Secretion of newly synthesized CSF was detectable 3-6 hours after stimulation and continued for approximately 24 h. Twenty minutes pulse exposure to LPS was sufficient to induce half maximum secretion of GM-CSF, and after 24-36 h the adherent monocytes could not be restimulated. Neither GM-CSF nor TNF could down-regulate the secretion of GM-CSF. IL-3 induced a minor secretion of GM-CSF whereas TNF, G-CSF, M-CSF and IFN-gamma were unable to induce GM-CSF secretion. In addition to LPS and IL-1, GM-CSF and to a minor degree TNF induced G-CSF secretion. Enriched T lymphocytes secreted GM-CSF, but not G-CSF, after stimulation with PHA or staphylococcal enterotoxin A (SEA), whereas LPS and IL-1 were without stimulatory effects. We also noted that enriched T lymphocytes added to LPS-stimulated adherent monocytes at ratios of 1:10 or more inhibited, in a dose-dependent fashion, GM-CSF secretion by 13-55%. These findings add new quantitative data on CSF secretion by human monocytes.

Cell Adhesion↗
PubMed1991

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in serum during induction treatment of acute leukaemia.

Granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) are increasingly used to stimulate granulopoiesis in neutropenic patients but in most cases without any knowledge of the endogenous CSF-levels. With the purpose to define serum levels of GM-CSF and G-CSF during induction chemotherapy and haematological reconstitution in patients with acute leukaemia we have used enzyme-linked immunosorbent assay (ELISA) techniques to measure these growth factors in 18 patients with acute myeloid leukaemia (AML) and eight patients with acute lymphoblastic or undifferentiated leukaemia (ALL/AUL). G-CSF above 0.05 ng/ml was detected in 54% of the analysed AML samples, median 0.29 (range 0.05-2.80) ng/ml; and in 40% of analysed ALL/AUL samples, median 0.09 (range 0.05-3.00) ng/ml. In patients with AML there was a clear correlation between an elevated serum concentration of G-CSF and documented infections. On the other hand, 15/18 of the patients with acute myeloid leukaemia and 8/8 patients with ALL/AUL had non-detectable levels of GM-CSF (less than 0.10 ng/ml). Two patients had measurable levels of GM-CSF in all samples, median 0.71 (range 0.26-1.18) ng/ml and in these patients the levels successively decreased during and after chemotherapy and did not increase in response to infections. In normals detectable levels of GM-CSF were found in 2/35 individuals and G-CSF in 0/10 individuals.

Acute Disease↗
PubMed1991

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in serum in bone marrow transplanted patients.

Colony-stimulating factors (CSF) are being increasingly used to accelerate hematopoietic recovery after bone marrow transplantation. To study the endogenous serum levels of CSF in bone marrow transplanted patients we have used immunoassays measuring granulocyte-macrophage colony-stimulating factor (GM-CSF) with a sensitivity of 0.10 ng/ml and granulocyte colony-stimulating factor (G-CSF) with a sensitivity of 0.05 ng/ml. Serum samples, taken from the conditioning treatment until engraftment, were analysed in 13 patients receiving allogeneic transplants and in eight patients receiving autologous transplants. Ten patients had acute myeloid leukemia, seven acute lymphoblastic leukemia, one acute undifferentiated leukemia, two non-Hodgkin's lymphoma and one multiple myeloma. Samples were taken 1-2 times before transplantation and 1-2 times per week after transplantation (median of 46 days in allotransplant recipients and 32 days in autotransplant recipients); 17% of the allogeneic transplanted patients and 35% of the autologous transplanted patients had detectable levels of G-CSF. In both types of transplantation the G-CSF concentrations were low: median 0.06 (range 0.05-0.14) and 0.08 (range 0.05-0.40) ng/ml respectively. GM-CSF was detected only in one analysed sample in all patients. There was no evidence of increased CSF levels related to engraftment or documented infections.

Acute Disease↗
PubMed1990

Tumor associated myelopoiesis inhibiting factors.

The best characterized hemopoietic growth inhibitors in myeloid leukemias are leukemia associated inhibitor (LAI) and leukemia inhibitory activity (LIA). Both are normal cell products overproduced in leukemia. LIA is identical to acid isoferritin and LAI is not identical to LIA. They act in different ways to inhibit normal stem cell growth. The over-production of these putative normal regulators may explain the suppression of normal hemopoiesis typical of myeloid leukemias. Modulation of the production and the action of LAI and LIA therefore have potential therapeutic value in leukemia.

Bone Marrow↗
PubMed1989

Cell-mediated inhibition of granulopoiesis in vitro in patients with acute myeloid leukemia in remission.

We investigated the in vitro granulopoiesis in 11 patients with acute myeloid leukemia (AML) in complete remission 3-80 months after diagnosis (median 8.5 months). 3 of the patients had subnormal levels of bone marrow-derived CFU-GM. 6 of 10 patients tested had defective recloning capacity of d-7 CFU-GM, suggesting a stem cell defect. Most patients (7/11) showed an increased colony growth of bone marrow-derived CFU-GM after T-cell depletion by E-rosetting, while readdition of isolated autologous T cells to T-cell depleted marrow caused a dose-dependent inhibition of colony formation; bone marrow T cells were more effective in this inhibition than peripheral blood T cells. Experiments using cells depleted of either CD4- or CD8-positive cells and CD4/CD8-enriched cell populations showed that both CD4- and CD8-positive cells had the capacity to inhibit colony growth. Long-term culture of bone marrow cells in suspension showed that the production of CFU-GM declined at about the same rate as in normal controls. Our findings suggest that there are persisting stem cell defects in patients with AML in remission and that the cell growth regulatory systems may be altered. These abnormalities could possibly be an effect of residual damage to the hematopoietic system caused by intensive chemotherapy.

Bone Marrow↗
PubMed1987

Modulation of the production of leukemia associated inhibitor (LAI) and its interaction with granulocyte-macrophage colony-forming cells.

Leukemia associated inhibitor, LAI, reversibly inhibits DNA synthesis in normal human granulocyte-macrophage colony-forming units (CFU-GM). LAI is produced by myeloid leukemia cells, a subpopulation of normal nonadherent low-density mononuclear cells in peripheral blood and bone marrow, as well as by the human promyelocytic cell line HL-60. Normal low-density marrow cell absorbed LAI at 37 degrees C from HL-60 cell-conditioned medium. When normal marrow cells were treated with trypsin or chymotrypsin they lost their capacity to absorb LAI and also became insensitive to the inhibitory effect of LAI. These observations were taken as circumstantial evidence for the existence of a trypsin-sensitive LAI receptor on normal marrow cells, including CFU-GM. Glucocorticoid steroids (hydrocortisone, prednisolone, and dexamethasone) inhibited LAI production by acute myeloid leukemia (AML) cells, normal LAI-producing cells, and HL-60 cells. The fact that prostaglandin E1 (PGE) totally inhibited LAI production by normal cells and that indomethacin abrogated the inhibitory effect of adherent cells on LAI production suggested a role for adherent monocytic cells and PGE in the regulation of LAI production.

Bone Marrow↗
PubMed1986

Defective recloning capacity of granulocyte-macrophage colony-forming cells in chronic myeloid leukaemia.

We investigated the recloning capacity of normal and chronic myeloid leukaemia granulocyte-macrophage colony-forming cells (CFU-GM) after 7 d culture in methylcellulose. Normal CFU-GM were recloned with the formation of 3.52 +/- 1.12 secondary CFU-GM per primary d-7 colony. A frequency distribution of the colony-forming cells within d-7 colonies showed a heterogeneous distribution with the majority of d-7 colonies containing 1 or zero CFU-GM and a few colonies containing more than 30 CFU-GM. Separation of marrow cells by velocity sedimentation demonstrated that the recloning capacity was primarily expressed by the smallest colony-forming cells. In contrast, marrow or blood cells from 18 patients with Ph1-chromosome-positive CML in the chronic phase produced colonies with defective recloning capacity. Only 1 patient had a recloning value within the normal range; the others had a mean value of 0.35 (range 0-1.28) secondary colonies per primary d-7 colony. The recloning defect was not related to WBC or treatment, since 5 newly diagnosed patients with CML also showed defective recloning before any treatment was given, which is compatible with the defect being an inherent property of CML.

Bone Marrow↗
PubMed1985

Production, characteristics and mode of action of hemopoietic growth inhibitors in myeloid leukemias.

The best characterized hemopoietic growth inhibitors in myeloid leukemias are leukemia associated inhibitor (LAI) and leukemia inhibitory activity (LIA). Both are normal cell products overproduced in leukemia. LIA is identical with acid isoferritins and LAI is not identical with LIA. They act in different ways to inhibit normal stem cell growth. The overproduction of these putative normal regulators may explain the suppression of normal hemopoiesis typical of myeloid leukemias. Modulation of the production and the action of LAI and LIA may have potential therapeutic value in leukemia.

Colony-Forming Units Assay↗
PubMed1985

Adenosine diphosphate ribosyl transferase in marrow cells of patients with acute myeloid leukemia is related to differentiation and drug sensitivity.

The levels of adenosine diphosphate ribosyl transferase (ADPRT) have been quantified in Ficoll-Isopaque isolated marrow cells from 36 patients with acute myeloid leukemia (AML). The in vitro growth pattern in agar at diagnosis was also determined, and in 16 patients the in vitro drug sensitivity of the clonogenic cells (CFU-GM) to cytosine arabinoside and daunorubicin was measured. The ADPRT activities of the various marrow cell preparations correlated to the morphological diagnoses, in vitro growth patterns, in vitro drug sensitivities to cytosine arabinoside, and to the prognoses of the AML patients. Hence, ADPRT may be a useful marker for the pathophysiology associated to AML.

Bone Marrow↗
PubMed1985

Density distribution of chronic myeloid leukaemia and normal colony-forming cells in diffusion chambers (CFU-D) and agar (CFU-GM).

The density distribution in Percoll gradients of clonogenic cells forming colonies in diffusion chambers (CFU-D) or in agar culture (CFU-GM) was studied in chronic myeloid leukaemia (CML). The density distribution of CFU-GM in CML was homogeneous with peaks within 1.058-1.061 g/ml, which is slightly lower than normal. CFU-D, on the other hand, showed heterogeneous distributions both in CML and in normal controls. Two separable populations of CFU-D were recognized, one with the same or lower density than CFU-GM that formed almost exclusively neutrophilic colonies in diffusion chambers, and a second population concentrating in the density range 1.068-1.075 g/ml which primarily formed macrophage colonies. The second population contained colony-forming cells derived from both Fc-receptor positive and Fc-receptor negative precursor cells, suggesting that at least some colonies in diffusion chambers arise from Fc-receptor positive granulopoietic cells of intermediate maturity and/or monocytes. The concentration of CFU-D in peripheral blood was increased 40- to 100-fold in 2 patients currently off treatment who had increased WBC counts.

Agar↗
PubMed1985

Mechanisms for adherence of eosinophils to an antibody-coated surface.

Eosinophils may act by degranulation after attachment to a surface. As the mechanisms of adherence are not understood, we have investigated the dependency on Fc(IgG) receptors and other mechanisms by studying the adherence of human eosinophils to albumin-Sepharose beads coated with either specific rabbit IgG antibody, F(ab')2 antibody fragments or serum under different conditions. Adherence to Sephadex beads and albumin-coated microtitration plates was also investigated. 50% of the eosinophils adhered spontaneously to all 3 different surfaces not coated with the antibody, whereas only 25% of neutrophils and less than 10% of mononuclear cells adhered. A small but significant increase in adherence to albumin-Sepharose or albumin-coated plastic occurred after addition of the IgG-antibody, but not after addition of F(ab')2 fragments, indicating that the Fc region was responsible for some increase in adherence. Incubation of eosinophils with IgG-Fc fragments prevented the additional antibody-mediated adherence. As Fc receptor-negative eosinophils adhered almost as well as Fc receptor-positive cells, it appears that the Fc receptors are of minor importance and instead, a nonspecific adherence mechanism, possibly unique for the eosinophil, seems to be the most important in eosinophil adherence to antibody-coated surfaces.

Animals↗
PubMed1985

Isolation of leukaemia-associated inhibitor (LAI)-producing cells from normal peripheral blood.

LAI, leukaemia-associated inhibitor, has previously been shown to be produced by a subpopulation of null cells in myeloid leukaemia, and has the capacity to suppress the proliferation of normal granulopoietic stem cells, CFU-GM, in vitro. In the present study, low density mononuclear cells from normal peripheral blood were separated into adherent/non-adherent, phagocytic/non-phagocytic, T-lymphocytes/non-T cells, and Fc-receptor positive and negative cells in search for LAI-producing cells in normal blood. Cell fractions enriched for NK-cells were isolated from Percoll gradients and NK-activity and LAI-production were assayed in the different fractions. Anti-Leu-2, anti-Leu-3, and anti-HLA-DR were used to deplete mononuclear cells of cells positive for these monoclonals using a panning technique. It is concluded from these studies that normal LAI-producing cells belong to a non-adherent, non-phagocytic, non-T, non-B, Fc-receptor positive population which does not express NK-activity, and which is Leu-2, Leu-3 and HLA-DR negative. The results imply that LAI may be a novel feedback regulator of the proliferative rate of granulopoietic stem cells and that LAI is produced by a small subpopulation of cells in both blood and bone marrow.

Antibodies, Monoclonal↗
PubMed1985

Effect of zinc and other cations on the release of the eosinophil cationic protein.

The eosinophil cationic protein, ECP, is a unique eosinophil granule constituent, which is released extracellularly after exposure of the eosinophils to a non-phagocytosable surface such as complement-coated Sephadex beads. The ECP is released to some extent even in the absence of Ca2+ and Mg2+, though both these cations augment the release reaction tested alone, and an optimal release is observed only in the presence of 2 mmol/l Ca2+ and 2 mmol/l Mg2+ in the medium. Zn2+ at concentrations from 0.25-4.0 mmol/l inhibited the release of ECP in a dose-dependent fashion, with or without Ca2+ and Mg2+ in the medium. Mn2+ had dual effects, stimulating the ECP release in the absence of Mg2+ and Ca2+, and inhibiting the release in the presence of these cations. Li1+ caused minor inhibition of ECP release, but only in the absence of Ca2+ and Mg2+. The inhibitory effect of Zn2+ was immediate and reversible after washing of the cells, suggesting that the inhibition is due to interaction with the plasma membrane functions.

Blood Proteins↗
PubMed1984

Characterization of the cells in myeloid leukemia that produce leukemia associated inhibitor (LAI) and demonstration of LAI-producing cells in normal bone marrow.

LAI (leukemia associated inhibitor) is a high mol. wt glycoprotein that reversibly reduces the proliferative rate of normal granulopoietic stem cells but not of clonogenic cells in leukemia. LAI was originally found to be produced and released by cells in acute and chronic leukemia and may play a role in the suppression of normal hematopoiesis in these diseases. We now report the physical and functional characteristics of LAI-producing cells in myeloid leukemia; they have a medium density with peaks in the range of 1.075-1.080 g/ml in continuous Percoll gradients, they are large cells with a sedimentation velocity of about 13-15 mm/h and they are non-phagocytic, non-adherent, non-T, non-B, Fc-receptor positive cells and about equally distributed among C'-receptor positive and negative cells. Normal bone marrow was shown to contain LAI-producing cells present in the non-phagocytic Fc-receptor positive compartment of cells within the density range 1.075-1.080 g/ml. Presented data suggest that LAI-producing cells comprise a subpopulation of cells that may be involved in the regulation of normal granulopoiesis as well as in the suppression of normal hematopoiesis in leukemia. These data also show that LAI-producing cells are different from the cells producing another inhibitor (LIA) recently identified as acidic isoferritins.

Bone Marrow↗
PubMed1984

Detection of lactoferrin and myeloperoxidase release from single neutrophils by a protein A plaque assay.

A haemolytic plaque assay was adopted to detect release of lactoferrin and myeloperoxidase (MPO) from single neutrophils. Target erythrocytes coated with protein A were bound as a monolayer by poly-L-lysine to the surface of a plastic dish. Secreted lactoferrin and MPO induced plaque formation dependent on the reaction with complement and specific antiserum producing lysis of the protein-A-coated sheep red blood cells. Lactoferrin was found to be released spontaneously from a fraction of neutrophils while MPO was released only after phagocytosis, reflecting different mechanisms for degranulation of MPO-containing azurophil and lactoferrin-containing specific granules.

Antibody-Producing Cells↗