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Type beta transforming growth factors promote interleukin-3 (IL-3)-
dependent differentiation of human basophils but inhibit IL-3-dependent
differentiation of human eosinophils
C Sillaber, K Geissler, R Scherrer, R Kaltenbrunner, P Bettelheim, K Lechner and P Valent
Medical Department, University of Vienna, Austria.
Basophils and eosinophils share a common differentiation pathway. Factors
regulating terminal commitment toward one cell type, however, have so far
not been defined. Interleukin-3 (IL-3) is a potent differentiation factor
for both human eosinophils and basophils. In the present study, the effects
of various recombinant human (rh) growth regulators on IL-3-dependent
growth of eosinophils and basophils were studied in a bone marrow (BM)
suspension culture system (normal donors, n = 13). We found that type beta
transforming growth factors (TGFs) lead to a significant increase in the
absolute numbers of basophils in BM cultures grown in the presence of IL-3
(day 14 of culture; IL-3: 133 +/- 20 v IL-3 + TGF-beta 1: 231 +/- 28 x
10(3)/mL [P less than .01]) and to an increase in the total histamine
values (IL-3: 72.6 +/- 22.2 v IL-3 + TGF-beta 1: 142.9 +/- 37.3 ng/mL [P
less than .015]) compared with rhIL-3 alone. In contrast, type beta TGFs
were found to inhibit the IL-3-dependent growth of eosinophils (IL-3: 170.4
+/- 37.2 v IL-3 + TGF-beta 1: 16.7 +/- 5.2 x 10(3)/mL [P less than .01])
and formation of eosinophil cationic protein in the same culture system.
The effect of TGF-beta 1 (and TGF-beta 2) on IL-3-dependent differentiation
of basophils and eosinophils was dose- and time-dependent (maximum effects
observed with 1 to 10 ng/mL of rhTGF-beta 1 or TGF-beta 2) and could be
neutralized by an antibody specific for TGF-beta 1. In contrast to the
TGFs, interferon-alpha (IFN-alpha) and IFN-gamma were found to downregulate
IL-3-dependent formation of both basophils (IL-3: 167 +/- 33 v IL-3 +
IFN-alpha: 67 +/- 25 v IL-3 + IFN-gamma: 65 +/- 33 x 10(3)/mL [P less than
.01]) and eosinophils (IL-3: 239 +/- 5 v IL-3 + IFN-alpha: 81 +/- 4 v IL-3
+ IFN-gamma: 67 +/- 17 x 10(3)/mL [P less than .05]) in our culture system.
Type beta TGFs as well as the IFNs failed to directly induce
differentiation of human basophils or eosinophils in the absence of other
growth factors. Together, these results show that type beta TGFs and IFNs
are potent regulators of cytokine-dependent growth and differentiation of
human allergic effector cells.
Volume 80,
Issue 3,
pp. 634-641,
08/01/1992
Copyright © 1992 by The American Society of Hematology
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