The interleukin-5 (IL-5) receptor is a heterodimer that consists of an IL-5 specific alpha subunit and a common ssc chain that is shared with the receptors for granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-3 (IL-3). In contrast to IL-5, which acts mainly as an eosinophil lineage specific factor in vivo, IL-3 and GM-CSF stimulate the survival, proliferation and development of various hematopoietic cell lineages and also multipotent progenitor cells. IL-5 has little effect on the survival or proliferation of the multipotent stem cell line FDCP-Mix A4 but does promote some eosinophil development. To investigate whether the lineage specificity of IL-5 is due to the restricted expression of the IL-5 receptor alpha subunit we transfected the FDCP-Mix A4 cells with a retroviral vector containing this alpha subunit. The ectopic expression of the IL-5 receptor alpha subunit in the FDCP-Mix cells did not increase the observed eosinophilic development but did stimulate survival and proliferation of the transfected cells when IL-5 was added. IL-5 thus acts like IL-3 in these cells, promoting proliferation and survival. The results suggest that IL-5, whilst having a capacity to promote proliferation, does not influence eosinophilic lineage commitment in these multipotent cells. The results further argue that the observed lineage specificity of IL-5 is probably due to factors in addition to the restricted expression of the IL-5 receptor alpha subunit.

REFERENCES

Bagley
C. J.
,
Woodcock
J. M.
,
Stomski
F. C.
,
Lopez
A. F.
(
1997
).
The structural and functional basis of cytokine receptor activation: lessons from the common beta subunit of the granulocyte-macrophage colony-stimulating factor, interleukin-3 (IL-3), and IL-5 receptors.
Blood
89
,
1471
1482
Fairbairn
L. J.
,
Cowling
G. J.
,
Reipert
B. M.
,
Dexter
T. M.
(
1993
).
Suppression of apoptosis allows differentiation and development of a multipotent hemopoietic cell line in the absence of added growth factors.
Cell
74
,
823
832
Gasson
J. C.
(
1991
).
Molecular physiology of granulocyte-macrophage colony-stimulating factor.
Blood
77
,
1131
1145
Gearing
D. P.
,
King
J. A.
,
Gough
N. M.
,
Nicola
N. A.
(
1989
).
Expression cloning of a receptor for human granulocyte-macrophage colony-stimulating factor.
EMBO J
8
,
3667
3676
Gorman
D. M.
,
Itoh
N.
,
Jenkins
N. A.
,
Gilbert
D. J.
,
Copeland
N. G.
,
Miyajima
A.
(
1992
).
Chromosomal localization and organization of the murine genes encoding the beta subunits (AIC2A and AIC2B) of the interleukin 3, granulocyte/macrophage colony-stimulating factor, and interleukin 5 receptors.
J. Biol. Chem
267
,
15842
15848
Hara
T.
,
Miyajima
A.
(
1992
).
Two distinct functional high affinity receptors for mouse interleukin-3 (IL-3).
EMBO J
11
,
1875
1884
Heldin
C. H.
(
1995
).
Dimerization of cell surface receptors in signal transduction.
Cell
80
,
213
223
Heyworth
C. M.
,
Dexter
T. M.
,
Kan
O.
,
Whetton
A. D.
(
1990
).
The role of hemopoietic growth factors in self-renewal and differentiation of IL-3-dependent multipotential stem cells.
Growth Factors
2
,
197
211
Heyworth
C. M.
,
Dexter
T. M.
,
Nicholls
S. E.
,
Whetton
A. D.
(
1994
).
Combinations of colony-stimulating factors promote enhanced proliferative potential in enriched granulocyte-macrophage colony-forming cells.
Exp. Hematol
22
,
1089
1094
Hitoshi
Y.
,
Yamaguchi
N.
,
Mita
S.
,
Sonoda
E.
,
Takaki
S.
,
Tominaga
A.
,
Takatsu
K.
(
1990
).
Distribution of IL-5 receptor-positive B cells. Expression of IL-5 receptor on Ly-1(CD5)+B cells.
J. Immunol
144
,
4218
4225
Hu
M.
,
Krause
D.
,
Greaves
M.
,
Sharkis
S.
,
Dexter
T. M.
,
Heyworth
C. M.
,
Enver
T.
(
1997
).
Multilineage gene expression preceeds commitment in the haemopoietic system.
Genes Dev
14
,
512
524
Itoh
N.
,
Yonehara
S.
,
Schreurs
J.
,
Gorman
D. M.
,
Maruyama
K.
,
Ishii
A.
,
Yahara
I.
,
Arai
K.
,
Miyajima
A.
(
1990
).
Cloning of an interleukin-3 receptor gene: a member of a distinct receptor gene family.
Science
247
,
324
327
Johnson
G. R.
,
Metcalf
D.
(
1980
).
Detection of a new type of mouse eosinophil colony by Luxol-fast-blue staining.
Exp. Hematol
8
,
549
561
Just
U.
,
Stocking
C.
,
Spooncer
E.
,
Dexter
T. M.
,
Ostertag
W.
(
1991
).
Expression of the GM-CSF gene after retroviral transfer in hematopoietic stem cell lines induces synchronous granulocyte-macrophage differentiation.
Cell
64
,
1163
1173
Karasuyama
H.
,
Melchers
F.
(
1988
).
Establishment of mouse cell lines which constitutively secrete large quantities of interleukin 2, 3, 4 or 5, using modified cDNA expression vectors.
Eur. J. Immunol
18
,
97
104
Kinoshita
T.
,
Yokota
T.
,
Arai
K.
,
Miyajima
A.
(
1995
).
Suppression of apoptotic death in hematopoietic cells by signalling through the IL-3/GM-CSF receptors.
EMBO J
14
,
266
275
Kitamura
T.
,
Sato
N.
,
Arai
K.
,
Miyajima
A.
(
1991
).
Expression cloning of the human IL-3 receptor cDNA reveals a shared beta subunit for the human IL-3 and GM-CSF receptors.
Cell
66
,
1165
1174
Kopf
M.
,
Brombacher
F.
,
Hodgkin
P. D.
,
Ramsay
A. J.
,
Milbourne
E. A.
,
Dai
W. J.
,
Ovington
K. S.
,
Behm
C. A.
,
Kohler
G.
,
Young
I. G.
, et al. 
(
1996
).
IL-5-deficient mice have a developmental defect in CD5+B-1cells and lack eosinophilia but have normal antibody and cytotoxic T cell responses.
Immunity
4
,
15
24
Laker
C.
,
Stocking
C.
,
Bergholz
U.
,
Hess
N.
,
De Lamarter
J. F.
,
Ostertag
W.
(
1987
).
Autocrine stimulation after transfer of the granulocyte/macrophage colony-stimulating factor gene and autonomous growth are distinct but interdependent steps in the oncogenic pathway.
Proc. Nat. Acad. Sci. USA
84
,
8458
8462
Lin
C. S.
,
Lim
S. K.
,
Dagati
V.
,
Costantini
F.
(
1996
).
Differential effects of an erythropoietin receptor gene disruption on primitive and definitive erythropoiesis.
Genes Dev
10
,
154
164
Markowitz
D.
,
Goff
S.
,
Bank
A.
(
1988
).
Construction and use of a safe and efficient amphotropic packaging cell line.
Virology
167
,
400
406
Markowitz
D.
,
Goff
S.
,
Bank
A.
(
1988
).
A safe packaging line for gene transfer: separating viral genes on two different plasmids.
J. Virol
62
,
1120
1124
Mckinstry
W. J.
,
Li
C. L.
,
Rasko
J. E.
,
Nicola
N. A.
,
Johnson
G. R.
,
Metcalf
D.
(
1997
).
Cytokine receptor expression on hematopoietic stem and progenitor cells.
Blood
89
,
65
71
Metcalf
D.
,
Burgess
A. W.
(
1982
).
Clonal analysis of progenitor cell commitment of granulocyte or macrophage production.
J. Cell Physiol
111
,
275
283
Mire-Sluis
A.
,
Page
L. A.
,
Wadhwa
M.
,
Thorpe
R.
(
1995
).
Evidence for a signaling role for the alpha chains of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5 receptors: divergent signaling pathways between GM-CSF/IL-3 and IL-5.
Blood
86
,
2679
2688
Mui
A. L.
,
Miyajima
A.
(
1994
).
Cytokine receptors and signal transduction.
Prog. Growth Factor Res
5
,
15
35
Nishinakamura
R.
,
Miyajima
A.
,
Mee
P. J.
,
Tybulewicz
V. L.
,
Murray
R.
(
1996
).
Hematopoiesis in mice lacking the entire granulocyte-macrophage colony-stimulating factor/interleukin-3/interleukin-5 functions.
Blood
88
,
2458
2464
Ogawa
M.
(
1993
).
Differentiation and proliferation of hematopoietic stem cells.
Blood
81
,
2844
2853
Sakamaki
K.
,
Miyajima
I.
,
Kitamura
T.
,
Miyajima
A.
(
1992
).
Critical cytoplasmic domains of the common beta subunit of the human GM-CSF, IL-3 and IL-5 receptors for growth signal transduction and tyrosine phosphorylation.
EMBO J
11
,
3541
3549
Sanderson
C. J.
(
1992
).
Interleukin-5, eosinophils, and disease.
Blood
79
,
3101
3109
Smith
A.
,
Metcalf
D.
,
Nicola
N. A.
(
1997
).
Cytoplasmic domains of the common beta-chain of the GM-CSF/IL-3/IL-5 receptors that are required for inducing differentiation or clonal suppression in myeloid leukaemic cell lines.
EMBO J
16
,
451
464
Spooncer
E.
,
Heyworth
C. M.
,
Dunn
A.
,
Dexter
T. M.
(
1986
).
Self-renewal and differentiation of interleukin-3-dependent multipotent stem cells are modulated by stromal cells and serum factors.
Differentiation
31
,
111
118
Stanley
E.
,
Lieschke
G. J.
,
Grail
D.
,
Metcalf
D.
,
Hodgson
G.
,
Gall
J. A.
,
Maher
D. W.
,
Cebon
J.
,
Sinickas
V.
,
Dunn
A. R.
(
1994
).
Granulocyte/macrophage colony-stimulating factor-deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology.
Proc. Nat. Acad. Sci. USA
91
,
5592
5596
Suda
T.
,
Suda
J.
,
Ogawa
M.
,
Ihle
J. N.
(
1985
).
Permissive role of interleukin 3 (IL-3) in proliferation and differentiation of multipotential hemopoietic progenitors in culture.
J. Cell Physiol
124
,
182
190
Takagi
M.
,
Hara
T.
,
Ichihara
M.
,
Takatsu
K.
,
Miyajima
A.
(
1995
).
Multi-colony stimulating activity of interleukin 5 (IL-5) on hematopoietic progenitors from transgenic mice that express IL-5 receptor alpha subunit constitutively.
J. Exp. Med
181
,
889
899
Takaki
S.
,
Kanazawa
H.
,
Shiiba
M.
,
Takatsu
K.
(
1994
).
A critical cytoplasmic domain of the interleukin-5 (IL-5) receptor alpha chain and its function in IL-5-mediated growth signal transduction.
Mol. Cell Biol
14
,
7404
7413
Tavernier
J.
,
Devos
R.
,
Cornelis
S.
,
Tuypens
T.
,
van der Heyden
J.
,
Fiers
W.
,
Plaetinck
G.
(
1991
).
A human high affinity interleukin-5 receptor (IL5R) is composed of an IL5-specific alpha chain and a beta chain shared with the receptor for GM-CSF.
Cell
66
,
1175
1184
van der Heyden
J.
,
Devos
R.
,
Plaetinck
G.
,
Fache
I.
,
Fiers
W.
,
Tavernier
J.
(
1991
).
Characterization of the murine IL-5 receptor complex with the use of a panel of monoclonal antibodies. Relationship to the murine IL-3 receptor.
J. Immunol
147
,
3413
3418
Whetton
A. D.
,
Heyworth
C. M.
,
Nicholls
S. E.
,
Evans
C. A.
,
Lord
J. M.
,
Dexter
T. M.
,
Owen-Lynch
P. J.
(
1994
).
Cytokine-mediated protein kinase C activation is a signal for lineage determination in bipotential granulocyte macrophage colony-forming cells.
J. Cell Biol
125
,
651
659
Woodcock
J. M.
,
McClure
B. J.
,
Stomski
F. C.
,
Elliott
M. J.
,
Bagley
C. J.
,
Lopez
A. F.
(
1997
).
The human GM-CSF receptor exists as a preformed complex that can be activated by GM-CSF, IL-3 or IL-5.
Blood
90
,
3005
3017
Wu
H.
,
Liu
X.
,
Jaenisch
R.
,
Lodish
H. F.
(
1995
).
Generation of committed erythroid BFU-E and CFU-E progenitors does not require erythropoietin or the erythropoietin receptor.
Cell
83
,
59
67
Yamaguchi
Y.
,
Suda
T.
,
Suda
J.
,
Eguchi
M.
,
Miura
Y.
,
Harada
N.
,
Tominaga
A.
,
Takatsu
K.
(
1988
).
Purified interleukin 5 supports the terminal differentiation and proliferation of murine eosinophilic precursors.
J. Exp. Med
167
,
43
56
Yoder
M. C.
,
Williams
D. A.
(
1995
).
Matrix molecule interactions with hematopoietic stem cells.
Exp. Hematol
23
,
961
967
Ziltener
H. J.
,
de St. Groth
B. F.
,
Leslie
K. B.
,
Schrader
J. W.
(
1988
).
Multiple glycosylated forms of T cell-derived interleukin 3 (IL-3). Heterogeneity of IL-3 from physiological and nonphysiological sources.
J. Biol. Chem
263
,
14511
14517
This content is only available via PDF.