Impairment of GM-CSF production in myelodysplastic syndromes.
In this study we evaluated the production of granulocyte/macrophage-colony stimulating factor (GM-CSF), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) by enriched bone marrow (BM) macrophages in 15 patients affected by myelodysplasia and 20 normal BM donors. The presence of GM-CSF, IL-6 and TNF-alpha in the culture supernatants of BM macrophages was detectable only after stimulation with lipopolysaccharide (LPS), whereas no differences were present in the amount of IL-6 and TNF-alpha between myelodysplastic patients and normal controls, GM-CSF production appeared eight-fold reduced in BM macrophage culture supernatants from myelodysplastic patients with respect to normal controls. After further experiments, we concluded that the impaired release of GM-CSF by BM macrophages could not be due to a different production kinetic in myelodysplastic patients. Moreover, the number of multipotent (CFU-GEMM), granulocyte/macrophage (CFU-GM) and erythroid (BFU-E) progenitors was significantly impaired in myelodysplastic patients. In conclusion, we demonstrated that the production of GM-CSF by purified adherent cells from MDS patients is markedly impaired in spite of the peripheral blood cytopenia. This selective defect in GM-CSF production, along with an intrinsic defect of haematopoietic progenitor cells, might contribute to the impairment of haematopoiesis always observed in myelodysplastic patients.
Visani
G
G
L. e A. Seragnoli Institute of Haematology, University of Bologna, Italy.
Zauli
G
G
Tosi
P
P
Fogli
M
M
Cenacchi
A
A
Finelli
C
C
Gamberi
B
B
Ottaviani
E
E
Manfoi
S
S
Tura
S
S
D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000276:immunology*; D002448:Cell Adhesion; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor