Aplastic anemia: evidence for dysfunctional bone marrow progenitor cells and the corrective effect of granulocyte colony-stimulating factor in vitro.
We investigated the effects of granulocyte-macrophage colony-stimulating factor, interleukin-3, stem cell factor, interleukin-6, and granulocyte colony-stimulating factor (G-CSF) alone, and in combination, on the clonogenic potential of normal and aplastic anemia (AA) bone marrow mononuclear cells (BMMC and CD34+ cells. AA BMMC consistently produced a significantly lower absolute number of colonies than normal, but, when account was taken of the reduced proportion of CD34+ cells in AA BM, there was no significant difference in terms of cloning efficiency (CE). However, when removed from the influence of accessory cells, the CE of AA CD34+ cells decreased significantly more than normal, indicating a defect in their function, either in terms of dependence on accessory cell-derived factors or susceptibility to cell damage when sorted. Of the factors studied, G-CSF had the most significant effect on the response of CD34+ cells from both groups when removed from their accessory cells. This was particularly true for AA CD34+ cells, whose response to cytokine stimuli containing G-CSF enabled them to match the response of normal CD34+ cells.
Scopes
J
J
Department of Cellular and Molecular Sciences, St. George's Hospital Medical School, London, UK.
Daly
S
S
Atkinson
R
R
Ball
S E
SE
Gordon-Smith
E C
EC
Gibson
F M
FM
D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000473:pathology*; D018952:Antigens, CD34 / Q000032:analysis; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology*; D003114:Colony-Forming Units Assay; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D019089:Stem Cell Factor / Q000494:pharmacology
D018952:Antigens, CD34; D007377:Interleukin-3; D015850:Interleukin-6; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor