Bone Marrow Hypoplasia During Intensive Care: Bone Marrow Culture Studies Implicating Ranitidine in the Suppression of Haemopoiesis

1987 ◽  
Vol 6 (6) ◽  
pp. 503-506 ◽  
Author(s):  
R.J. Amos ◽  
B. Kirk ◽  
J.A.L. Amess ◽  
A.L. Jones ◽  
C.J. Hinds
Keyword(s):  
Bone Marrow ◽  
Renal Failure ◽  
Intensive Care ◽  
Colony Growth ◽  
Drug Accumulation ◽  
Normal Bone Marrow ◽  
Normal Bone ◽  
Bone Marrow Hypoplasia ◽  
Macrophage Colony ◽  
Seriously Ill Patients

Two seriously ill patients with renal failure developed bone marrow hypoplasia and peripheral blood cytopenias during admission to an Intensive Care Unit (ICU). Both patients were being treated with ranitidine and, in both, there was evidence of drug accumulation. Serum from the patient with the highest concentration of ranitidine inhibited granulocyte-macrophage colony growth from normal bone marrow. The addition of ranitidine to cultures of normal bone marrow also produced a concentration-dependent inhibition of colony growth. Ranitidine should be used with caution in patients with renal failure where drug accumulation may seriously impair bone marrow function.

scholarly journals Interleukin-1 alpha also induces granulocyte-macrophage colony- stimulating factor in immature normal bone marrow cells

Blood ◽  
1990 ◽  
Vol 76 (2) ◽  
pp. 307-311 ◽  
Author(s):  
FJ Bot ◽  
P Schipper ◽  
L Broeders ◽  
R Delwel ◽  
K Kaushansky ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Interleukin 1 ◽  
Tnf Alpha ◽  
Normal Bone Marrow ◽  
Bone Marrow Blast ◽  
Gm Csf ◽  
Normal Bone ◽  
Blast Cells ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony

The cytokine interleukin-1 (IL-1) plays a role in the regulation of normal as well as leukemic hematopoiesis. In acute myeloid leukemia (AML), IL-1 induces autocrine granulocyte/macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF) production, and these factors may then synergistically induce proliferation in AML blast cells. In this report, we show that IL-1 stimulates DNA synthesis of highly enriched normal bone marrow blast cells (CD34 positive, adherent cell depleted, CD3/CD14/CD15 negative). The stimulative effect of IL-1 can be blocked with neutralizing anti-TNF alpha and anti-GM-CSF antibodies and, most efficiently, by the combination of anti-TNF alpha and anti-GM-CSF, but not with anti-G-CSF antibody, suggesting that IL-1- induced proliferation was initiated through TNF and GM-CSF release. Concentrations of TNF and GM-CSF increased in the culture medium of normal bone marrow blast cells after IL-1 induction. Of the IL-1- induced cells, 12% were positive for GM-CSF mRNA by in situ hybridization, as opposed to 6% of non-induced cells. Thus, in addition to its effect on leukemic blast cells, IL-1 also acts on normal marrow blast cells. We propose a scheme where IL-1 stimulation of normal bone marrow blast cells leads to the induction of TNF alpha and GM-CSF, which in association stimulate DNA synthesis efficiently according to a paracrine or autocrine mechanism within the marrow blast cell compartment.

scholarly journals Expression and function of the human granulocyte-macrophage colony- stimulating factor receptor alpha subunit

Blood ◽  
1994 ◽  
Vol 84 (12) ◽  
pp. 4174-4185 ◽  
Author(s):  
PT Jubinsky ◽  
AS Laurie ◽  
DG Nathan ◽  
J Yetz-Aldepe ◽  
CA Sieff
Keyword(s):  
Bone Marrow ◽  
Normal Bone Marrow ◽  
Colony Stimulating Factor ◽  
Receptor Alpha ◽  
Gm Csf ◽  
Normal Bone ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
And Function ◽  
Stimulating Factor

To determine the expression and function of the granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha chain (GMR alpha) during hematopoiesis and on leukemic cells, monoclonal antibodies were raised by immunizing mice with cells expressing high levels of human GMR alpha. A pool of five antibodies isolated from three different mice was used to characterize GMR alpha. This antibody pool (anti-GMR alpha) immunoprecipitated a protein with the expected molecular weight of GMR alpha from COS cells transiently transfected with the GMR alpha gene. In factor-dependent cells, GMR alpha existed as a phosphoprotein. However, its phosphorylation was not stimulated by the presence of GM- CSF. Anti-GMR alpha inhibited the GM-CSF-dependent growth of cell lines and normal bone marrow cells and inhibited the binding of iodinated GM- CSF to its receptor. Cell surface expression of GMR alpha was examined using anti-GMR alpha and flow cytometry. GMR alpha was readily detectable on both blood monocytes and neutrophils. In adherence- depleted normal bone marrow, two separate populations expressed GMR alpha. The most positive cells were predominantly macrophages, whereas the cells that expressed less GMR alpha were largely myelocytes and metamyelocytes. A small population of lin-CD34+ or CD34+CD38- cells also expressed GMR alpha, but they were not capable of significant growth in colony-forming assays. In contrast, the majority of lin-CD34+ and CD34+CD38- cells were GMR alpha-, yet they produced large numbers of myeloid and erythroid colonies in the same assay. Malignant cells from patients with leukemia were also tested for GMR alpha expression. All of the myeloid leukemias and only rare lymphoid leukemias surveyed tested positive for GMR alpha. These results show that anti-GMR alpha is useful for the functional characterization of the GMR alpha and for the detection of myeloid leukemia and that GMR alpha is expressed on certain lineages throughout hematopoietic development; however, progenitors that express the receptor may have a reduced capacity to proliferate in response to hematopoietic growth factors.

scholarly journals Inhibition of human erythropoietic colony formation in culture by treatment with Ia antisera.

1978 ◽  
Vol 148 (2) ◽  
pp. 613-618 ◽  
Author(s):  
R J Winchester ◽  
P A Meyers ◽  
H E Broxmeyer ◽  
C Y Wang ◽  
M A Moore ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Colony Formation ◽  
Inhibitory Effect ◽  
Low Density ◽  
Normal Bone Marrow ◽  
Density Fractions ◽  
Normal Bone ◽  
Lymphoid Lines ◽  
Macrophage Colony

Incubation with Ia antiserum, followed by complement, markedly inhibited erythroid colonies arising from hematopoietic cells present in the nonadherent low density fractions of normal bone marrow. Both erythropoietin-dependent colonies and bursts were eliminated at dilutions of antiserum equivalent to, or greater than the dilutions required to abolish the granulocyte-macrophage colony formation. The inhibitory effect of the Ia antiserum was abolished by absorption with B but not T cells from lymphoid lines. Available evidence suggested that Ia determinants are expressed on the erythropoietin-sensitive progenitors of the erythroid series in precise analogy to their sequence of expression on the granulocyte lineage. In both lineages, as shown previously, the Ia determinants become undetectable during subsequent stages of differentiation.

scholarly journals Interleukin-1 alpha also induces granulocyte-macrophage colony- stimulating factor in immature normal bone marrow cells

Blood ◽  
1990 ◽  
Vol 76 (2) ◽  
pp. 307-311 ◽  
Author(s):  
FJ Bot ◽  
P Schipper ◽  
L Broeders ◽  
R Delwel ◽  
K Kaushansky ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Interleukin 1 ◽  
Tnf Alpha ◽  
Normal Bone Marrow ◽  
Bone Marrow Blast ◽  
Gm Csf ◽  
Normal Bone ◽  
Blast Cells ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony

Abstract The cytokine interleukin-1 (IL-1) plays a role in the regulation of normal as well as leukemic hematopoiesis. In acute myeloid leukemia (AML), IL-1 induces autocrine granulocyte/macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF) production, and these factors may then synergistically induce proliferation in AML blast cells. In this report, we show that IL-1 stimulates DNA synthesis of highly enriched normal bone marrow blast cells (CD34 positive, adherent cell depleted, CD3/CD14/CD15 negative). The stimulative effect of IL-1 can be blocked with neutralizing anti-TNF alpha and anti-GM-CSF antibodies and, most efficiently, by the combination of anti-TNF alpha and anti-GM-CSF, but not with anti-G-CSF antibody, suggesting that IL-1- induced proliferation was initiated through TNF and GM-CSF release. Concentrations of TNF and GM-CSF increased in the culture medium of normal bone marrow blast cells after IL-1 induction. Of the IL-1- induced cells, 12% were positive for GM-CSF mRNA by in situ hybridization, as opposed to 6% of non-induced cells. Thus, in addition to its effect on leukemic blast cells, IL-1 also acts on normal marrow blast cells. We propose a scheme where IL-1 stimulation of normal bone marrow blast cells leads to the induction of TNF alpha and GM-CSF, which in association stimulate DNA synthesis efficiently according to a paracrine or autocrine mechanism within the marrow blast cell compartment.

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