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Institute of Molecular Medicine for the Prevention of Human Diseases, Research Center for Immunology and Autoimmune Diseases, University of Texas-Houston Health Science Center, Houston, TX.
To identify additional members of the murine
N-formyl-Met-Leu-Phe peptide receptor family (fMLF-R), a
mouse macrophage cDNA library was screened using the open reading frame
of murine N-formyl peptide receptor. Four individual
hybridizing cDNA clones were maintained through tertiary screening. One
cDNA clone was a truncated, polyadenylated version of the previously
described murine-fMLF-R. The other three cDNA clones varied in length,
but contained identical open reading frame sequences. One clone, 8C10,
was selected for further study and shared 70% sequence identity with
murine-fMLF-R and 89% sequence identity with murine lipoxin A4
receptor cDNA. When placed into the pcDNA-3 expression vector and
cotransfected with G
16 cDNA into COS-1 cells, 8C10 cDNA induced the
production of inositol-1,4,5-triphosphate when concentrations of
1–1600 nM lipoxin A4 (LXA4) were tested as ligands. Northern blot
analysis of murine organs indicated that the 8C10 message is present in
lung, spleen, and adipose tissue. Moreover, mice treated with LPS
demonstrated increased expression of 8C10 message in spleen and adipose
tissue, while showing a slight reduction in lung. We have also
characterized the 8C10 structural gene from a 129Sv/J genomic library
and have determined its size to be >6.1 kb in length and comprised of
two exons separated by a 4.8-kb intron. Collectively, these data
indicate that this homologue receptor is closely related to the murine
LXA4 receptor and functionally responds to LXA4 as a
ligand.
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