Antiproliferative and differentiative effects of recombinant interleukin-4
on a granulocyte colony-stimulating factor-dependent myeloblastic leukemic
cell line
Y Imai, N Nara, S Tohda, K Nagata, T Suzuki, M Nagasawa, I Murohashi and N Aoki
First Department of Internal Medicine, Tokyo Medical and Dental University,
Japan.
The effect of recombinant human interleukin-4 (IL-4) on a granulocyte
colony-stimulating factor (G-CSF)-dependent human myeloblastic leukemic
cell line, OCI-AML1a, was investigated. IL-4 suppressed the clonogenic cell
growth in methylcellulose culture, inhibited the uptake of 3H thymidine in
a dose-dependent manner at 5 to 100 U/mL, and consequently suppressed the
growth of clonogenic cells in short- and long-term suspension cultures. In
addition, IL-4 markedly increased the number of adherent cells. These
adherent cells were alpha-naphthyl-butyrate (alpha-NB) esterase-positive
and showed macrophage-like appearance, increased expression of CD14, CD11b,
CD23, and Ia, and significantly decreased clonogenicity. On the other hand,
nonadherent cells growing in suspension showed only slight increase in
proportion of alpha-NB esterase-positive or monocyte/macrophage-like cells
and increased CD23 expression by an addition of IL-4. The clonogenicity of
the nonadherent cells was not significantly influenced by IL-4. By addition
of the media conditioned by OCI-AML1a cells in the presence of IL-4, the
clonogenic cells growth of OCIAML1a cells was suppressed and adherent cells
were markedly increased. The suppressive and differentiative effects on
OCI/AML1a cells of the conditioned media and IL-4 itself were almost
completely abolished by anti-IL-4 antibody. Furthermore, the neutralizing
antibodies against transforming growth factor-beta 2 (TGF-beta 2), tumor
necrosis factor-alpha (TNF-alpha), or IL-6 did not influence the effect of
recombinant IL-4. Taken together, IL-4 was shown to suppress the growth and
induce differentiation toward adherent macrophage-like cells of the
G-CSF-dependent myeloblastic cell line. The effect of IL-4 may be direct,
and not secondary via inducing production of other cytokines such as
TGF-beta, TNF-alpha, or IL-6 by leukemic cells.
Volume 78,
Issue 2,
pp. 471-478,
07/15/1991
Copyright © 1991 by The American Society of Hematology
