Volume 270,
Number 33,
Issue of August 18, pp. 19495-19500, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
Molecular
Cloning and Functional Expression of a Novel CC Chemokine Receptor cDNA
from a Human Basophilic Cell Line
(Received for publication, May 5, 1995; and in revised form, May 15, 1995)
Christine A.
Power ,
Alexandra
Meyer,
Karin
Nemeth ,
Kevin B.
Bacon ,
Arlene
J.
Hoogewerf,
Amanda E. I.
Proudfoot,
Timothy
N. C.
Wells
We report the cloning and characterization of a novel basophil
CC chemokine receptor, K5-5, from the human immature basophilic
cell line KU-812. The predicted protein sequence of K5-5 shows
only 49% identity to the macrophage inflammatory protein-1
/RANTES
receptor (CC CKR-1) and 47% identity to monocyte chemotactic protein-1
receptor (b form), suggesting that this cDNA encodes a novel member of
the CC chemokine receptor family. Analysis of K5-5 mRNA
expression indicates that it is restricted to leukocyte-rich tissues.
In addition, we have shown significant levels of K5-5 mRNA in
human basophils, which were up-regulated by treatment with
interleukin-5. The CC chemokines, macrophage inflammatory
protein-1
, RANTES, and monocyte chemotactic protein-1 were able to
stimulate a Ca
-activated chloride channel in Xenopus laevis oocytes injected with K5-5 cRNA, whereas
no signal was detected in response to monocyte chemotactic protein-2,
macrophage inflammatory protein-1
, or the CXC chemokine,
interleukin-8. Taken together, these results indicate for the first
time the presence of a CC chemokine receptor on basophils, which
functions as a ``shared'' CC chemokine receptor and may
therefore be implicated in the pathogenesis of basophil-mediated
allergic diseases.