Myelodysplastic syndrome (MDS)-associated inhibitory activity on haematopoietic progenitor cells: contribution of monocyte-derived lipid containing macrophages (MDLM).
We studied myelodysplastic syndrome-associated inhibitory activity (MDS-IA), which inhibited colony formation in vitro of normal granulocyte-macrophage progenitors (CFU-GM). When adherent marrow cells were incubated with fetal calf serum for 21-24 d, monocyte-derived lipid containing huge macrophages (MDLM) developed. MDLM from MDS marrow (MDS-MDLMs) and their conditioned medium (MDLM-CM) consistently suppressed the growth of normal CFU-GM colony formation. MDS-IA was active on CFU-GM during the S-phase and relatively resistant to heating. Monoclonal antibody against H subunit (acidic) ferritin and polyclonal antibody against placental ferritin neutralized the inhibitory activity of MDS-MDLMs. In addition, cell lysates of MDS-MDLMs reacted to both monoclonal anti-H subunit ferritin and polyclonal anti-placental ferritin in Western blotting analysis, indicating that the inhibitory activity was predominantly acidic isoferritin. On the other hand, MDLMs obtained from normal bone marrow had a CFU-GM enhancing activity. These results suggest that MDS-MDLMs may be responsible for the suppression of granulopoiesis in patients with MDS and that the suppression may be mediated by soluble factors, notably H subunit isoferritin.
Ohmori
M
M
Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Ueda
Y
Y
Masutani
H
H
Hirama
T
T
Anzai
N
N
Yoshida
Y
Y
Okuma
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D005293:Ferritins / Q000276:immunology / Q000502:physiology; D006098:Granulocytes / Q000473:pathology / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000473:pathology* / Q000502:physiology; D006801:Humans; D008055:Lipids / Q000032:analysis*; D008264:Macrophages / Q000737:chemistry / Q000473:pathology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology* / Q000502:physiology; D009190:Myelodysplastic Syndromes / Q000097:blood* / Q000473:pathology / Q000503:physiopathology
D000911:Antibodies, Monoclonal; D008055:Lipids; D005293:Ferritins