Possible involvement of bone marrow stromal cells in agranulocytosis caused by vesnarinone treatment.
Vesnarinone, an oral therapeutic agent for cardiac failure, causes agranulocytosis as a side effect. To elucidate the mechanism of occurrence of the agranulocytosis, we examined the effect of vesnarinone on granulopoiesis using an in vitro human long-term bone marrow culture system. Addition of vesnarinone to the culture decreased the total number of hematopoietic cells, mainly composed of mature granulocytes and macrophages, but increased the number of granulocyte-macrophage progenitor cells (CFU-GM) and CD33-CD34+ cells as compared with an untreated control. Differentiation of CFU-GM was induced by removing the agent from the culture medium, indicating that the effect of vesnarinone was reversible. The agent did not directly affect CFU-GM in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF). Furthermore, treatment of stromal cells with vesnarinone repressed the production of G, GM, M-CSF, suggesting that the agent may cause a hematopoietic disorder, agranulocytosis, through the impairment of stromal cell function.
Aizawa
S
S
Department of Anatomy, Nihon University School of Medicine, Tokyo, Japan.
Nakano
M
M
Yaguchi
M
M
Kuriyama
Y
Y
Iwase
O
O
Toyama
K
K
Tanaka
K
K
Hoshi
H
H
Sugimoto
K
K
Kaido
A
A
Imai
T
T
Nabeshima
R
R
Handa
H
H
D000380:Agranulocytosis / Q000139:chemically induced*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D011719:Pyrazines; D011804:Quinolines / Q000009:adverse effects*; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects
D000970:Antineoplastic Agents; D016207:Cytokines; D011719:Pyrazines; D011804:Quinolines; C041667:vesnarinone