From the
Interleukin 13 (IL-13) shares many biological properties with
IL-4, and although the receptor for IL-4 (IL-4R) has been
characterized, the expression and structure of IL-13 receptor are
unknown. We report here that human renal cell carcinoma (RCC) cells
express large numbers of functional IL-13R. Human B lymphocytes and
monocytes expressed a very small number of IL-13R, while resting or
activated human T cells expressed little or no IL-13R. IL-4 did not
compete for IL-13 binding, while IL-13 competed for IL-4 binding, even
though IL-4R and IL-13R are structurally distinct on human RCC cells.
IL-13 cross-linked with one major protein that is similar in size to
the
IL-13
Despite the knowledge of
many effects of IL-13, the receptor for IL-13 (IL-13R) has not been
reported on. It was hypothesized that the
We have previously demonstrated that human renal cell
carcinoma (RCC) cells express high affinity IL-4R
(19) . Since
many of the observed effects of IL-13 are similar to those of IL-4, we
have examined RCC cells for the expression of IL-13R. We demonstrate
that human RCC cells express large numbers of functional IL-13R and
that IL-4 and IL-13 interact with each other's receptors. We
provide evidence that IL-13R and IL-4R on RCC cells are composed of
different subunits and that IL-13R is mainly composed of a single
protein similar in size to the smaller of the two IL-4R subunits. The
IL-13R protein does not cross-react with anti-
For binding experiments, typically 1
Although IL-13 responsiveness has previously been
reported in human monocytes, B cells, and premyeloid (TF-1) cells
(2, 3, 4, 5, 6, 7, 8, 9, 10, 11) ,
little is known about IL-13R structure or its binding char-acteristics
in these cells. Our results show that freshly isolated human monocytes,
Epstein-Barr virus-transformed B cell line, and TF-1 cell line express
very few IL-13 binding sites (100-300 binding sites/cell)
compared with human RCC cells (). On the other hand, no
binding of
We also
investigated whether IL-13 competes for the IL-4 binding on lymphoid
MLA 144 cells or RAJI cell lines. These cells were incubated with
radiolabeled IL-4 with or without excess unlabeled IL-4 or IL-13. As
shown in Fig. 3, A and B,
The lack of association of
Our data indicate that
IL-13R do not associate with
Finally, the expression of IL-13R on human RCC cells may
provide a unique antigen that can be used for many diagnostic or
therapeutic purposes. For example, radionuclides conjugated to IL-13 or
to an antibody to IL-13R may be useful for nuclear medicine scanning
diagnosis of RCC. Similarly, IL-13R may be targets for many
receptor-directed therapeutics. We have observed that other human solid
tumors also express IL-13R that are internalized following binding to a
ligand consisting of IL-13 and Pseudomonas exotoxin.
We thank P. Leland and H. Mostowski for expert
technical assistance and flow cytometric analysis, respectively; Dr. P.
Munson (NIH) for help in designing binding experiments and statistical
interpretation of the IL-13 binding data using the LIGAND program; Dr.
G. Haas (Wayne State University, Detroit, MI) for PM-RCC cells; Dr. P.
Burd (Center for Biologics Evaluation and Research (CBER)) for TF1.J6
cells; G. Tosato (CBER) for DH cells; Chiron Corp. (Emerryville, CA)
for IL-2 and Dr. I. Pastan (National Cancer Institute) for helpful
discussions and critical reading of this manuscript.
ABSTRACT
INTRODUCTION
EXPERIMENTAL PROCEDURES
RESULTS AND DISCUSSION
FOOTNOTES
ACKNOWLEDGEMENTS
REFERENCES
subunit of IL-2, -4, -7, -9, and -15 receptors
but was not recognized by anti-
or anti-IL-4R
antibodies. IL-4, on the other hand, cross-linked with two major
proteins, the smaller of which appears to be similar in size to IL-13R
and
, but (like the IL-13R) it did not react with
anti-
antibody. Although as shown in this study and in
previous studies,
is a functional component of IL-4R
in lymphoid cells, it does not appear to be associated with IL-4R on
RCC cells. Even in the absence of common
chain IL-4 and IL-13
were able to up-regulate intracellular adhesion molecule-1 antigen on
RCC cells. These data suggest that the interaction of IL-13 with IL-4R
does not involve
and IL-13R itself may be a novel
subunit of the IL-4R.
(
)
is a 12-kDa lymphokine that has
been cloned from activated T cells
(1, 2) . The gene for
IL-13 is closely linked to the IL-4 gene
(3) , and IL-13 protein
has been shown to have a 30% identity in the amino acid sequence to
IL-4 protein
(4) . IL-13 shares many biological properties with
IL-4. Like IL-4, it inhibits the production of inflammatory cytokines
(2, 5) and up-regulates major histocompatibility
complex class II and CD23 expression on monocytes
(6) .
Similarly, on B cells, IL-13 enhances proliferative responses to
anti-IgM and anti-CD40 antibodies, major histocompatibility complex
class II, and CD23 expression, induces anti-CD40-dependent IgE class
switch, and induces IgG and IgM synthesis
(2, 7, 8, 9, 10) . In sharp
contrast to IL-4, IL-13 has been shown not to affect resting or
activated T cells
(9, 11) .
subunit of the IL-2
receptor (IL-2R
)
(12, 13) , which is
associated with IL-4, IL-7, IL-9, and IL-15
(14, 15, 16, 17, 18) receptors,
may also be associated with IL-13R
(12, 13, 14, 15, 31) . In
addition, others have suggested that IL-4R and IL-13R may share a
common component that appears to function in signal transduction
(4) .
or
anti-IL-4R antibodies. Similarly, to our surprise, the smaller of the
two IL-4R proteins does not react with anti-
antibody.
These results suggest that
chain is not associated
with IL-13R or IL-4R on human RCC cells and further suggest that IL-13R
is a monomeric or dimeric protein, which itself may be a novel subunit
of IL-4R.
Cytokines and Reagents
Recombinant human IL-13
(2) was kindly provided by Dr. A. Minty (Sanofi Elf Bio
Recherches, Laberge, France). For some experiments, we used recombinant
human IL-13 expressed in Escherichia coli and produced by one
of us (W. D.). Prior to use, we compared IL-13 prepared from the two
sources and found that they were identical in biological activity
( i.e. support of TF-1 cell proliferation) as well as in their
ability to displace I-IL-13 from the cell surface.
Recombinant human IL-4 was provided by Paul Trotta (Schering-Plough
Research Institute, Kenilworth, NJ). A polyclonal rabbit antibody to
the high affinity human IL-4R (P7) was a kind gift from Immunex
Corporation (Seattle, WA). The antibodies to human IL-4 and
intercellular adhesion molecule (ICAM-1) were purchased from Genzyme
Corp. (Boston, MA) and AMAC, Inc. (Westbrook, ME), respectively. The
ICAM-1 cDNA probe, a 1.9-kilobase cDNA cloned from stimulated HL-60
cells
(20) , was a gift from Dr. Steve Shaw (NCI, Bethesda, MD).
Cells
The primary cultures of renal cell carcinoma
cell lines WS-RCC, HL-RCC, and MA-RCC were established in our
laboratory and are maintained as described previously
(19) .
TF-1 cell line, a human premyeloid erythroleukemic cell line that
responds to various cytokines including IL-13
(4) , and other
cells were cultured in RPMI 1640 medium containing 10% fetal bovine
serum glutamine (2 m
M), sodium pyruvate (1 m
M),
essential amino acids (1 m
M), penicillin (100 units/ml), and
streptomycin (100 µg/ml).
Radioreceptor Binding Assay
Recombinant human IL-4
and recombinant human IL-13 were labeled with I (Amersham
Corp.) by using the IODO-GEN reagent (Pierce) according to the
manufacturer's instructions. The specific activity of the
radiolabeled cytokines was estimated to range from 20 to 100
µCi/µg of protein.
10
RCC tumor cells were incubated at 4 °C for 2
h with
I-IL-13 (100 p
M) with or without
increasing concentrations (up to 500 n
M) of unlabeled IL-13.
In some experiments, IL-13R expression was examined as described
previously
(19) . The data were analyzed with the LIGAND program
(21) to determine receptor number and binding affinity.
Affinity Cross-linking Studies
Cells (5
10
) were labeled with
I-IL-13 or
I-IL-4 in the presence or absence of excess IL-13 or IL-4
for 2 h at 4 °C. The bound ligand was cross-linked to its receptor
with disuccinimidyl suberate (Pierce) at a final concentration of 2
m
M for 30 min. Cells were lysed in a buffer containing 1%
Triton X-100, 1 m
M phenylmethylsulfonyl fluoride, 0.02 m
M leupeptin, 5.0 µ
M trypsin inhibitor, 10 m
M benzamidine HCl, 1 m
M phenanthroline iodoacetamide, 50
m
M aminocaproic acid, 10 µg/ml pepstatin, and 10 µg/ml
aprotinin. The cell lysates were cleared by boiling in sample buffer
containing 2-mercaptoethanol and analyzed by electrophoresis through 8%
SDS-polyacrylamide gel. The gel was subsequently dried and
autoradiographed. In some experiments, the receptor-ligand complex was
immunoprecipitated from the lysate overnight at 4 °C by incubating
with protein A-Sepharose beads that had been preincubated with P7
anti-human IL-4R or anti-
antibody and analyzed as
above.
Flow Cytometric Analysis
RCC cells were cultured
with IL-13 (10 ng/ml) over a 48-h period, washed, and incubated at 4
°C for 60 min with anti-human ICAM-1 antibody (84H10). Control
cells were incubated in staining buffer alone or with isotype control
(IgG) antibody. Cells were then washed and stained for 60
min with a secondary antibody consisting of F(ab`)
fragment
of mouse IgG conjugated to fluorescein isothiocyanate. After washing,
cells were analyzed on FACScan/C32 equipment (Becton Dickinson, San
Jose, CA) using a LYSIS II program. Fluorescence intensity was
expressed as mean channel number on a 256-channel/10
log
scale.
Northern Blot Analysis
Equal amounts of total RNA
were examined by Northern blot analysis
(19, 22) . The
membrane was probed with P-labeled cDNA for
or ICAM-1 at 42 °C for 18 h. In some experiments, the
membrane was stripped and probed with a cDNA probe for
glyceraldehyde-3-phosphate dehydrogenase.
Expression of IL-13R
Four human RCC lines
(WS-RCC, HL-RCC, PM-RCC, and MA-RCC) that were examined bound
I-IL-13 specifically, and the density of IL-13R varied
from 2100 sites/cell in WS-RCC cells to 150,000 sites/cell in HL-RCC
cells (Fig. 1 and ). Scatchard analyses
(23) revealed that only one affinity class of receptors was
expressed on each cell line. The binding affinities
( K
) ranged between 100 p
M and
400 p
M in three RCC cell lines, while HL-RCC cells expressed
lower affinity receptors ( K
3
n
M).
I-IL-13 was observed on H9 T cells, LAK cells,
and resting or phytohemagglutinin-activated peripheral blood
lymphocyte. This is compatible with the fact that IL-13 responsiveness
has not been observed in T lymphocytes
(9, 11) .
Interaction of IL-13 and IL-4 with IL-13R and
IL-4R
Recently, it was proposed that IL-2R is
associated with IL-13R
(14, 15, 17, 18) and that IL-13R may share a common component with IL-4R
(4, 24) . To directly address these possibilities, we
first performed radioligand binding experiments on HL-RCC and WS-RCC
cells using
I-IL-4 or
I-IL-13 in the
presence or absence of excess of either cytokine. Our results (Fig. 2)
show that unlabeled IL-4 more efficiently inhibited
I-IL-4 from binding to RCC cells (84 and 72% displacement
of total binding in WS-RCC and HL-RCC, respectively) than IL-13, which
also displaced
I-IL-4 binding to these cells (61% of
total binding in WS-RCC and 51% in HL-RCC) under similar conditions. On
the other hand, while
I-IL-13 binding was effectively
displaced by IL-13 (about 85% of the total in both cell types), it was
only minimally displaced by IL-4 (12% of total displacement in WS-RCC
and 7% in HL-RCC). These results indicate that IL-4 and IL-13 both
interact with each other's receptors; however, the interaction is
not identical, since IL-4 inhibition of
I-IL-13 binding
was weak and IL-13 inhibition of
I-IL-4 binding was not
complete. Our results agree with previous observations in which IL-13
was found to compete with IL-4 binding on TF-1 cells
(4) .
However, in that report the converse experiment was not done. Here we
provide results showing that even though IL-13 competed for IL-4
binding, IL-4 did not compete for IL-13 binding.
I-IL-4
bound to MLA 144 and RAJI cells, and excess unlabeled IL-4 effectively
displaced radiolabeled IL-4, while excess IL-13 could not compete this
binding. This observation is at variance to that seen with RCC cells in
which IL-13 competed for IL-4 binding. The inability of IL-13 to
compete for
I-IL-4 binding to MLA 144 is consistent with
our observation that IL-13 did not bind to peripheral blood T (or MLA
144) cells. However, the inability of IL-13 to compete for IL-4 binding
on the RAJI (B cell lineage) cell line is not clear. As discussed
below, these cells express common
chain, and it is possible that
common
chain interferes with the binding of IL-13. Studies are
under way to address this point.
Figure 3:
Lack of competition of
I-IL-4 binding by IL-13 on MLA 144 and RAJI cells. MLA
144 cells ( A) or RAJI (Burkitt's lymphoma) cells
( B) were incubated with 0.5 n
M of
I-IL-4 in the absence or presence of 200-fold molar
excess (RAJI) or various concentrations (up to 1000-fold molar excess)
of IL-13 (MLA 144). Total
I-IL-4 bound was 4569 ±
36 cpm on MLA 144 cells and 9975 ± 283 cpm on RAJI cells.
Subunit Structure of IL-13R and IL-4R
We next
investigated the subunit structure of IL-13R on RCC cells by
cross-linking studies. Our results indicate that I-IL-13
cross-linked to one major protein on all four RCC cells and that the
complex migrated as a single broad band ranging between 68 and 80 kDa
(Fig. 4, A and B). A single band was also observed on
human premyeloid TF-1.J61 cells (Fig. 4 B) only after much
longer exposure of the gel. After subtracting the molecular mass of
IL-13 (12 kDa), the size of the IL-13 binding protein was estimated at
56-68 kDa. The
I-IL-13 cross-linked band was not
observed when the cross-linking was performed in the presence of a
200-fold molar excess of IL-13 (Fig. 4, A, lanes 2 for each tumor cell line, and B, lane 2). In addition to the major band, a faint band of
approximately 45 kDa was also observed in HL-RCC and PM-RCC but not on
MA-RCC cells (Fig. 4 A). This band appeared to be
specifically associated with IL-13R, because unlabeled IL-13 competed
for the binding of
I-IL-13. This band could represent an
IL-13R-associated protein or a proteolytic fragment of the larger band.
In contrast to the displacement of
I-IL-13 binding by
unlabeled IL-13 (Fig. 2), an excess of unlabeled IL-4 did not
prevent the appearance of IL-13R band in RCC cell lines
(Fig. 4 A, lanes 3 for each tumor).
IL-13 on the other hand competed for
I-IL-4 binding to
both major proteins on WS-RCC cells (Fig. 4 C, lane 3). It is of interest that
I-IL-13
cross-linked protein was slightly larger in size in TF-1.J61, WS-RCC,
PM-RCC, and HL-RCC cell lines compared with that seen in MA-RCC (Figs.
4, A and B, and 5, A and B).
Post-translational modifications, such as glycosylation or
phosphorylation, may account for this difference.
Figure 4:
SDS-polyacrylamide gel electrophoresis
analysis of I-IL-13
IL-13R or
I-IL-4
IL-4R complexes. Five million RCC cells
( A) or nine million TF1.J61 cells ( B) were labeled
with
I-IL-13 in the absence or presence of 200-fold molar
excess of unlabeled IL-13 or IL-4. MA-RCC, HL-RCC, and PM-RCC cells
were incubated with
I-IL-13 alone ( A, lane 1 of each tumor type) or in the presence of excess IL-13
( A, lane 2 of each tumor type, or
B, lane 2) or IL-4 ( A, lane 3 of each tumor type). WS-RCC cells were incubated with 1
n
M
I-IL-4 alone ( C, lane 1) or in the presence of excess IL-4 ( C,
lane 2) or IL-13 ( C, lane 3). The radiolabeled ligand was cross-linked to its
receptor and analyzed by SDS-polyacrylamide gel electrophoresis and
autoradiographed for 2 days ( A), 6 days ( B), or
4-19 days ( C).
Figure 2:
Competition of I-IL-4 or
I-IL-13 binding. RCC cells (1
10
)
were incubated with
I-IL-4 (0.64 n
M) or
I-IL-13 (0.64 n
M) with or without excess IL-4
(128 n
M) or IL-13 (128 n
M). Competition for
radioligand binding is expressed as percentage of total binding. Total
I-IL-4 bound to two RCC cell cultures was 17,832 ±
1099 and 14,631 ± 780 cpm ± S.D. for HL-RCC and WS-RCC,
respectively, and total binding of
I-IL-13 was 49,945
± 3164 and 8119 ± 122 cpm ± S.D. to HL-RCC and
WS-RCC cells, respectively.
Immunoprecipitation of IL-13R and IL-4R
To
characterize the relationship between IL-4R and IL-13R, we
immunoprecipitated I-IL-13
IL-13R and
I-IL-4
IL-4R complexes with the polyclonal anti-IL-4R
antibody, P7, which has been used to immunoprecipitate IL-4R subunits
(14) . Our results show that anti-IL-4R did not
co-immunoprecipitate IL-13R on MA-RCC cells (Fig. 5 A, lane 3) or WS-RCC cells (Fig. 5 B, lane 3). Thus, IL-13R is not immunoreactive with the
anti-IL-4R antibody. However, as expected, anti-IL-4R antibody
immunoprecipitated IL-4R (140 and 75 kDa) on WS-RCC cells
(Fig. 5 C, lane 1), which express IL-4R
(19) .
Figure 5:
Immunoprecipitation of IL-13R and IL-4R.
RCC or MLA 144 cells were labeled with 1 n
M either
I-IL-13 or
I-IL-4 in the absence or
presence of unlabeled IL-13 or IL-4. The cell lysates were incubated
with the anti-IL-4R (P7) or anti-
antibody overnight
at 4 °C to immunoprecipitate IL-4R or
and
analyzed on SDS-polyacrylamide gel electrophoresis. A,
radiolabeled IL-13 bound to MA-RCC cells in the absence ( lane 1) or presence ( lane 2) of excess
unlabeled IL-13 or immunoprecipitated with anti-IL-4R ( lane 3) or anti-
antibody ( lane 4). B,
I-IL-13 cross-linked to
WS-RCC cells in the absence ( lane 1) or presence
( lane 2) of excess unlabeled IL-13 or
immunoprecipitated with IL-4R ( lane 3) or
antibody ( lane 4). C,
I-IL-4 cross-linked to WS-RCC cells in the absence
( lane 1) or presence ( lane 2) of
excess IL-4 or immunoprecipitated with antibody to IL-4R ( lanes 1 and 2) or to
( lane 3). Lane 4 represents
immunoprecipitation of
I-IL-4-labeled receptors on
MLA-144 cells by anti-
antibody. D, Northern
analysis of
mRNA expression. Total cellular RNA was
extracted from three RCC (WS-RCC, MA-RCC, and CAKI-1), two T cell
lymphoma, one B-cell Burkitt's lymphoma cell line, or a murine
fibroblast cell line (L cells), and 20 µg was electrophoresed
through 1% agarose/formaldehyde denaturing gel. These were then probed
with a
P-labeled
cDNA (30) and exposed
to autoradiographic film for 2 days.
We next immunoprecipitated IL-13R and IL-4R on RCC
cells with anti-antibody. Antibody to the IL-2R
has been shown to co-immunoprecipitate IL-4R and
IL-7R
(14, 16) . However, this antibody did not
immunoprecipitate the IL-13R on MA-RCC cells (Fig. 5 A,
lane 4) or on WS-RCC (Fig. 5 B,
lane 4). As a control, anti-
did
immunoprecipitate the IL-4R bands on lymphoid MLA 144 cells
(14) (Fig. 5 C, lane 4).
Although
has been shown to be associated with IL-4R
on lymphoid cells
(14, 15) , it does not appear to be
associated with the IL-4R on WS-RCC tumor cells because
anti-
did not immunoprecipitate IL-4R on these cells
(Fig. 5 C, lane 3). The absence of
expression on RCC tumor cells was substantiated by
Northern analysis. All three RCC cell lines examined were negative for
mRNA, while lymphoid cells were strongly positive
(Fig. 5 D).
chain with IL-4R in RCC cells is a novel and surprising
observation. But interestingly, in the absence of
chain, IL-4Rs were functional on these cells as IL-4 inhibited
their proliferation in vitro (19) and modulated ICAM-1
antigen expression
(
)
(shown below). Similarly, we
previously demonstrated that murine L cells, which constitutively
express IL-4R, do not express common
chain
(14) . However, the introduction of
chain into these cells
caused the phosphorylation of IRS-1, which was not observed in
untransfected cells, indicating that
chain is
necessary at least for IRS-1 phosphorylation. These data suggest that
IL-4 may involve at least two independent signaling pathways. The
involvement of two independent signaling pathways has also been
previously suggested
(25, 26) . In addition, in a recent
study utilizing monocytic cell lines (Mono Mac 6 and THP-1) that have
many properties in common with normal human monocytes, it was
demonstrated that IL-4 caused signaling even though these cells did not
express common
chain by polymerase chain reaction
(12, 27) . These data indicate that IL-4R is comprised
of different receptor components in different cell types and that they
are able to signal by different pathways.
chain of IL-2, IL-4,
IL-7, IL-9, and IL-15R in RCC cells. Since RCC cells did not express
this chain, it is possible that
chain associates with
IL-13R in other cells. The possible association of IL-13R with
chain was considered in cells that expressed this
subunit. Human B cells and T cells, including MLA 144 cells, have been
shown to express
chain
(14, 15) .
Since these cells expressed no or only about 100-300 IL-13
binding sites/cell and very few bound ligand cross-links to the
receptor, it is difficult to analyze receptor structure by
cross-linking studies. However, the fact that IL-13 did not compete for
IL-4 binding on these cells suggests that common
chain does not associate with IL-13R. In addition, the minimal
binding of
I-IL-13 to cells expressing
chain also suggests that
chain does not
interact with IL-13R.
Functional Significance of IL-13R Expression on Human RCC
Cells
We have previously shown that RCC cells express high
levels of ICAM-1 antigen on their cell surface, which is up-regulated
by IL-4.As shown in Fig. 6, A and
B, WS-RCC and PM-RCC expressed significant basal levels of
ICAM-1, and treatment with IL-13 significantly increased this
expression. The IL-13 modulation of ICAM-1 expression was also evident
at the mRNA level as shown in Fig. 6 C. When these data
were normalized to glyceraldehyde-3-phosphate dehydrogenase, we
observed that IL-13 induced a 44% increase in ICAM-1 mRNA levels
compared with 32% by IL-4 and 224% by a positive control, IFN-
.
These data demonstrate that IL-13 on RCC cells is functional.
Figure 6:
Effect of IL-13 on ICAM-1 expression on
RCC cells. WS-RCC ( A) or PM-RCC cells ( B) were
incubated in medium alone or in medium containing IL-13 (10 ng/ml) for
48 h. Cells were then analyzed for ICAM-1 expression by flow cytometry.
Cells from control and IL-13-treated groups showed identical patterns
when analyzed using isotype control antibody. Data from single
experiments are shown. Experiments were repeated 2-6 times with a
similar result. C, WS-RCC cells were cultured with or without
IL-13, IL-4, or interferon- ( IFN
) for 48 h. Total
RNA from these cells was electrophoresed (15.6 µg/lane) and
hybridized with a
P-labeled cDNA probe for ICAM-1. For
densitometric scanning, the blot was stripped and reprobed with a
P-labeled cDNA for glyceraldehyde-3-phosphate
dehydrogenase ( GAPDH) as an internal standard. We quantitated
the bands on a densitometer and compared the ICAM-1 bands after
normalizing them with their corresponding glyceraldehyde-3-phosphate
dehydrogenase bands. Results shown are representative of three
experiments.
Conclusion
We have demonstrated that human RCC
cells express between 15- and 500-fold higher numbers of functional
high or intermediate affinity IL-13R than normal immune cells. Although
IL-13 appears to interact with IL-4R, IL-4 has minimal interaction with
IL-13R. The subunit structure of IL-13R appears to be different from
that of IL-4R. I-IL-13 cross-links to a major protein of
56-68 kDa, while
I-IL-4 cross-links to two
different proteins of 140 and 75 kDa. Even though the sizes of IL-13R
and one of the two proteins of the IL-4R are similar to those of the
subunit of IL-2R, IL-4R, IL-7R, IL-9R, and IL-15R,
anti-
antibody did not cross-react with IL-13R or with
IL-4R on RCC cells. The absence of
was confirmed by
the lack of mRNA for
in RCC cells. These data suggest
that the composition of IL-4R on RCC cells is different from that on
immune cells that do express
chain. Because of the
similarity in the molecular size of IL-13R and one subunit of IL-4R, it
is possible that IL-13R is a component of the IL-4R, which may be one
explanation for how IL-13 can interact with IL-4R in RCC cells as shown
in this study and in TF-1 cells as shown by Zurawski et al. (4) . Further studies are needed to support or refute this
hypothesis.
(
)
The large numbers of IL-13R on
RCC cells and the apparent paucity of IL-13R on normal cells should
make RCC or other solid tumor cells preferential targets for the
cytotoxic effects of these and similar tumoricidal chimeric molecules.
Table: Expression of IL-13R on human cells
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.