PARC

4 Pages·0.168 MB·English

by  Nomiyama H., Yoshie O.

PARC
Hisayuki Nomiyama1,* and Osamu Yoshie2
1Department of Biochemistry, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto,
860-0811, Japan
2Department of Bacteriology, Kinki University School of Medicine, 377-2 Ohno-Higashi,
Osaka-Sayama, Osaka, 589-8511, Japan
*corresponding author tel:[phone], fax:[phone],
e-mail: [email protected]
DOI: 10.1006/rwcy.2000.11008.
SUMMARY and of monocytes activated with IL-4 plus glucocor-
ticoid (alternatively activated macrophages) (Kodelja
et al., 1998), and were termed DC-CK1 and AMAC-
PARC is a CC chemokine that shows the highest
1, respectively. By exon trapping, Guan et al. (1999)
sequence similarity to the CC chemokine MIP-1(cid:11). It
identified an exon from YACs containing the CC
is expressed in lung and lymphoid tissues, and
chemokine gene cluster and isolated the PARC/MIP-
induced in monocytes by TH2-associated cytokines.
4 cDNA using the exon sequence as probe.
In contrast to MIP-1(cid:11) and most other CC chemo-
kines, PARC is not chemotactic for monocytes and
granulocytes. Since PARC attracts only a subset of
Alternative names
T lymphocytes and is expressed in dendritic cells of
lymphoid tissues, one of the functions of PARC may
DC-CK1 (dendritic-cell-derived CC chemokine 1)
be the generation of primary immune responses. The
(Adema et al., 1997)
humangeneforPARC(SCYA18)residesinthemajor
MIP-4 (macrophage inflammatory protein 4) (Wells
CC chemokine cluster at chromosome 17q11.2, while
and Peitsch, 1997)
other lymphocyte-specific CC chemokine genes are
AMAC-1 (alternative macrophage activation-asso-
located on chromosomes other than chromosome 17.
ciated CC-chemokine 1) (Kodelja et al., 1998).
The mouse ortholog of PARC might not exist in the
CCL18 (CC chemokine ligand 18) (Zlotnik and
mouse genome.
Yoshie, 1999)
BACKGROUND Structure
Discovery
PARC is a CC chemokine containing four conserved
cysteine residues, and is most similar to the CC
PARC (pulmonary and activation-regulated chemo- chemokine MIP-1(cid:11). Although the overall similarity
kine) was cloned and reported independently by five between PARC and MIP-1(cid:11) is very high (61% iden-
groups. By searching the GenBank EST database for tity),theN-terminalsequencesbetweentheN-termini
sequences related to MIP-1(cid:11), Hieshima et al. (1997) of the mature proteins and the first of the two ad-
and Wells and Peitsch (1997) identified overlapping jacent cysteine residues are quite different (Figure 1).
cDNAs encoding a novel chemokine that they desig- Since chemokine N-terminal sequences are of critical
nated PARC and MIP-4, respectively. The cDNAs importanceininteractionwithreceptors,thissequence
encoding the same chemokine were isolated from difference may explain why PARC and MIP-1(cid:11) do
cDNAlibrariesofdendriticcells (Ademaetal.,1997) not share a receptor.
1228 Hisayuki Nomiyama and Osamu Yoshie
Figure 1 Amino acid comparison of the human PARC and MIP-1(cid:11).
Main activities and Cells and tissues that express
pathophysiological roles the gene
As for the activities and pathophysiological roles of In spite of the close similarity to MIP-1(cid:11), the
PARC, only the chemotactic activity and calcium expression pattern of PARC is quite different from
mobilization are reported (see section on In vitro that of MIP-1(cid:11). PARC mRNA is expressed
activities). constitutively at high levels in lung and at low levels
in some lymphoid tissues such as lymph node,
thymus, and appendix (Hieshima et al., 1997; Guan
et al., 1999), while MIP-1(cid:11) is expressed mainly in
GENE AND GENE REGULATION
spleen and PBL. By in situ hybridization, PARC
mRNA is shown to be expressed in alveolar
Accession numbers
macrophages and dendritic cells in T cell areas and
germinal centers of secondary lymphoid tissues
GenBank: (Adema et al., 1997; Hieshima et al., 1997). PARC
Human cDNA: NM_002988 mRNA is induced in monocytes by granulocyte–
Human gene: AB012113 macrophage colony-stimulating factor (GM-CSF)
plus IL-4 (dendritic cells) (Adema et al., 1997;
Brossart et al., 1998; Kodelja et al., 1998; Sallusto
Chromosome location et al., 1999), by lipopolysaccharide (Hieshima et al.,
1997; Reape et al., 1999; Sallusto et al., 1999) and by
TH2-associated cytokines such as IL-4, IL-10, and
By analysis of a previously constructed YAC contig
IL-13 (Kodelja et al., 1998), and the expression is
(Hieshimaetal.,1997)andbyconstructionofaBAC
inhibitedbyIFN(cid:13) (Kodeljaetal.,1998).Inductionof
contig (Maho et al., 1999; Tasaki et al., 1999), the
PARC expression was observed in K562, U937, and
human PARC gene was mapped within one of the
KG1 cell lines by PMA treatment (Hieshima et al.,
two subclusters in the CC chemokine gene cluster at
1997; St. Louis et al., 1999).
chromosome 17q11.2, and is located in the close
vicinity of the MIP-1(cid:11) gene.
PROTEIN
Relevant linkages
Accession numbers
Human chromosome 17q11.2
tel–(AT744.2/SCYA4L1–LD78(cid:12)/SCYA3L1–LD78(cid:13)/ SwissProt:
SCYA3L2)–MIP-1(cid:12)/SCYA4–MIP-1(cid:11)/SCYA3–PARC/ Human: P55774
SCYA18–MPIF-1/SCYA23–Leukotactin-1/SCYA15–
HCC-1/SCYA14–LEC/SCYA16–RANTES/SCYA5–
Sequence
MCP-4/SCYA13–I-309/SCYA1–MCP-2/SCYA8–
eotaxin 1/SCYA11–MCP-3/SCYA7–MCP-1/SCY-
A2–cen. See Figure 1.
PARC 1229
Description of protein IN VIVO BIOLOGICAL
ACTIVITIES OF LIGANDS IN
Mature protein
ANIMAL MODELS
length: 69
molecular weight: 7855
Normal physiological roles
isoelectric point: 9.39
When PARC was injected into the peritoneal cavity
Important homologies
ofmice,bothCD4+andCD8+Tcellswereattracted
(Guan et al., 1999).
ThemostcloselyrelatedchemokinestoPARCarethe
human CC chemokine MIP-1(cid:11)/CCL3 (61% identity)
and LD78(cid:12)/CCL3L1 (60% identity). Sequence anal- PATHOPHYSIOLOGICAL ROLES
ysis suggested that the PARC gene was generated by
IN NORMAL HUMANS AND
fusion of two MIP-1(cid:11)-like genes with selective usage
DISEASE STATES AND
of exons (Tasaki et al., 1999).
DIAGNOSTIC UTILITY
CELLULAR SOURCES AND
Role in experiments of nature and
TISSUE EXPRESSION
disease states
Cellular sources that produce
Usingreversetranscriptasepolymerasechainreaction
and in situ hybridization, gene expression for PARC
So far, there are no reports on cellular sources of
wasdetectedinhumanatheroscleroticplaques(Reape
PARC protein.
et al., 1999). PARC mRNA was restricted to CD68+
macrophages.
RECEPTOR UTILIZATION
References
The receptor for PARC has not yet been identified.
PARC binds to none of the following chemokine
Adema, G. J., Hartgers, F., Verstraten, R., de Vries, E.,
receptors:CCR1,CCR2B,CCR3,CCR4,andCCR5.
Marland, G., Menon, S., Foster, J., Xu, Y., Nooyen, P.,
McClanahan, T., Bacon, K. B., and Figdor, C. G. (1997).
A dendritic-cell-derived C-C chemokine that preferentially
IN VITRO ACTIVITIES
attractsnaiveTcells.Nature387,713–717.
Brossart, P., Grunebach, F., Stuhler, G., Reichardt, V. L.,
In vitro findings Mohle, R., Kanz, L., and Brugger, W. (1998). Generation of
functional human dendritic cells from adherentperipheral
blood monocytes by CD40 ligation in the absence of granu-
PARC is shown to be chemotactic for both activated locyte–macrophage colony-stimulating factor. Blood 92,
(CD3+) T cells and nonactivated (CD14(cid:255)) lympho- 4238–4247.
Guan, P., Burghes, A. H., Cunningham, A., Lira, P.,
cytes, but not for monocytes or granulocytes
Brissette, W. H., Neote, K., and McColl, S. R. (1999).
(Hieshima et al., 1997). Adema et al. (1997) reported
Genomic organization and biological characterization of the
thatPARCpreferentiallyattractsnaı¨verestingTcells novel human CC chemokine DC-CK-1/PARC/MIP-4/
(CD45RA+). PARC also induced an increase in the SCYA18.Genomics56,296–302.
level of intracellular free calcium in CD4+, CD8+, Hieshima, K., Imai, T., Baba, M., Shoudai, K., Ishizuka, K.,
Nakagawa, T., Tsuruta, J., Takeya, M., Sakaki, Y.,
and naı¨ve T cells (Guan et al., 1999).
Takatsuki, K., Miura, R., Opdenakker, G., Van Damme, J.,
Yoshie, O., and Nomiyama, H. (1997). A novel human CC
chemokine PARC that is most homologous to macrophage-
Bioassays used
inflammatory protein-1(cid:11)/LD78(cid:11) and chemotactic for T lym-
phocytes,butnotformonocytes.J.Immunol.159,1140–1149.
To determine the target cell specificity of PARC, Kodelja,V.,Muller,C.,Politz,O.,Hakij,N.,Orfanos,C.E.,and
Goerdt, S. (1998). Alternative macrophage activation-asso-
chemotaxisassay(Ademaetal.,1997;Hieshimaetal.,
ciatedCC-chemokine-1,anovelstructuralhomologueofmacro-
1997) and intracellular calcium flux measurement
phage inflammatory protein-1(cid:11) with a TH2-associated
(Guan et al., 1999) were performed. expressionpattern.J.Immunol.160,1411–1418.
1230 Hisayuki Nomiyama and Osamu Yoshie
Maho, A., Carter, A., Bensimon, A., Vassart, G., and Smoot, D. S., Kaushal, S., Grimes, J. L., Harlan, D. M.,
Parmentier,M.(1999).PhysicalmappingoftheCC-chemokine Chute, J. P., June, C. H., Siebenlist, U., and Lee, K. P.
geneclusteronthehuman17q11.2region. Genomics 59,213– (1999). Evidence for distinct intracellular signaling pathways
223. in CD34+progenitor to dendritic cell differentiation from a
Reape, T. J., Rayner, K., Manning, C. D., Gee, A. N., humancelllinemodel.J.Immunol.162,3237–3248.
Barnette, M. S., Burnand, K. G., and Groot, P. H. (1999). Tasaki,Y.,Fukuda,S.,Iio,M.,Miura,R.,Imai,T.,Sugano,S.,
Expression and cellular localization of the CC chemokines Yoshie, O., Hughes, A. L., and Nomiyama, H. (1999).
PARC and ELC in human atherosclerotic plaques. Am. J. ChemokinePARCgene(SCYA18)generatedbyfusionoftwo
Pathol.154,365–374. MIP-1(cid:11)/LD78(cid:11)-likegenes.Genomics55,353–357.
Sallusto,F.,Palermo,B.,Lenig,D.,Miettinen,M.,Matikainen,S., Wells,T.N.C.,andPeitsch,M.C.(1997).Thechemokineinfor-
Julkunen, I., Forster, R., Burgstahler, R., Lipp, M., and mation source: identification and characterization of novel
Lanzavecchia, A.(1999).Distinctpatternsandkineticsofche- chemokines using the WorldWideWeb and expressed sequence
mokine production regulate dendritic cell function. Eur. J. tagdatabases.J.Leukoc.Biol.61,545–550.
Immunol.29,1617–1625. Zlotnik, A., and Yoshie, O. (2000). Chemokines: a new classi-
St. Louis, D. C., Woodcock, J. B., Fransozo, G., Blair, P. J., fication system and their role in immunity. Immunity 12,
Carlson, L. M., Murillo, M., Wells, M. R., Williams, A. J., 121–127.