close

Вход

Забыли?

вход по аккаунту

?

6135.Catron D. Zlotnik A. - CCL28 (2001).pdf

код для вставкиСкачать
CCL28
Daniel J. Catron1 and Albert Zlotnik2,*
1
Department of Molecular Pathology, DNAX Research Institute of Molecular and
Cellular Biology Inc., 901 California Avenue, Palo Alto, CA 94304-1104, USA
2
Eos Biotechnology Inc., 225A Gateway Boulevard, South San Francisco, CA 94080, USA
* corresponding author tel: (650) 246-2313, fax: (650) 583-3881, e-mail: azlotnik@eosbiotech.com
DOI: 10.1006/rwcy.2001.1127.
Chapter posted 5 November 2001
SUMMARY
CCL28 is a member of the CC family of chemokines.
It is found on human chromosome 5 and on murine
chromosome 13. Both human and mouse CCL28
have six cysteines, four of which are conserved by
other CC chemokines. CCL28 displays chemotactic
activity for resting CD4 and CD8 T cells. CCL27
and CCL28 share the chemokine receptor CCR10,
formerly known as GPR2.
BACKGROUND
Discovery
An EST for CCL28 was identified by performing
a homology-based search (TBLASTN) against the
GenBank2 dbEST database using a human chemokine consensus query sequence (Wang et al., 2000).
The clone containing the EST was obtained through
the IMAGE Consortium (clone 136910) and
sequenced to confirm the presence of a full-length
open reading frame. Mouse CCL28 was cloned from
a kidney cDNA library from Rag-1 knockout mice
using the full-length human CCL28 as a probe.
Human and mouse CCL28 are highly conserved,
being 83% identical at the amino acid level and 76%
identical at the nucleotide level.
Alternative names
CCL28 is the systematic ligand nomenclature as
described by Zlotnik and Yoshie (2000) while
Cytokine Reference
SCYA28 is the systematic gene nomenclature.
Another report called this chemokine MEC, for
mucosa-associated chemokine (Pan et al., 2000).
Structure
No structural studies have been reported on CCL28.
Main activities and
pathophysiological roles
Recombinant human CCL28 attracts resting CD4
and CD8 T cells. The marked expression of CCR10
and CCL28 in the gastrointestinal tract suggests
possible roles in the homeostasis and inflammatory
responses of the gastrointestinal system (Wang et al.,
2000).
GENE AND GENE REGULATION
Accession numbers
Mouse CCL28: AF220238
Human CCL28: AF220210
Chromosome location
Mouse CCL28 maps to a distal region of chromosome 13 according to interspecific backcross analysis.
This region is syntenic with human chromosome 5q.
Copyright # 2001 Academic Press
2
Daniel J. Catron and Albert Zlotnik
As such, human CCL28 is the first chemokine to map
to chromosome 5.
Discussion of crystal structure
No structural studies have been reported.
Cells and tissues that express the
gene
Northern blotting indicates human CCL28 is predominantly expressed in prostate, colon, spleen, and to
a lesser degree by peripheral blood leukocytes. Mouse
CCL28 is predominantly expressed in testes and less
so in the kidney and brain. Using real time
quantitative PCR (TaqMan2 ), human CCL28 is
shown to be expressed in lymphoid and hematopoietic
libraries. Human and mouse CCL28 is most highly
expressed by normal and pathological cells of the
colon. TaqMan assays also showed mouse CCL28 to
be highly expressed in mesenteric lymph nodes, Peyer's
patches, and stomach cells. Immunohistochemical
staining suggests that epithelial cells produce CCL28.
Important homologies
The CC chemokines with the greatest degree of
homology to CCL28 are CCL27/CTACK, CCL25/
TECK, CCL17/TARC, CCL20/MIP-3, and
CCL19/MIP-3.
Posttranslational modifications
While CCL28 is glycosylated in its native form,
it is unknown if this affects the activity of the
protein.
CELLULAR SOURCES AND
TISSUE EXPRESSION
PROTEIN
Accession numbers
Cellular sources that produce include epithelial cells
and some leukocyte subsets.
Mouse CCL28: AAF87206
Human CCL28: AAF87205
RECEPTOR UTILIZATION
Sequence
See Figure 1.
Description of protein
Both human and mouse CCL28 contain six cysteines.
There are two cysteine residues in addition to the four
conserved ones normally found in CC chemokines. It
is hypothesized that the additional disulfide bond
might confine the extended C-terminal tail to the
body of the chemokine.
The CCL28 receptor has been identified as the former
orphan receptor GPR2, now called CCR10. Realtime, quantitative PCR (TaqMan2 ) was used to
determine expression levels in various cDNA libraries
derived from various human organs and cell types.
CCR10 is expressed in dermal microvascular
endothelial cells, dermal fibroblasts, melanocytes,
T cells, and skin-derived Langerhans cells. In organs,
CCR10 is most highly expressed in the small intestine
and colon and to a lesser degree in fetal liver, fetal
lung, fetal spleen, fetal testes, fetal brain, and uterus,
among others (Homey et al., 2000; Jarmin et al.,
Figure 1 Mouse and human CCL28 amino acid sequences.
Mouse CCL28:
MQQAGLTLMA VAVCVAFQTS EAILPMASSC CTEVSHHVSG RLLERVSSCS IQ
RADGDCDL AAVILHVKRR RICISPHNRT LKQWMRASEV KKNGRENVCS GKK
QPSRKDR KGHTTRKHRT RGTHRHEASR
Human CCL28:
MQQRGLAIVA LAVCAALHAS EAILPIASSC CTEVSHHISR RLLERVNMCR IQR
ADGDCDL AAVILHVKRR RICVSPHNHT VKQWMKVQAA KKNGKGNVCH RK
KHHGKRNS NRAHQGKHET YGHKTPY
CCL28
2000). CCR10 is also the receptor for CCL27.
Calcium flux experiments show CCL28 is able to
specifically desensitize human and mouse CCR10transfectants to CCL27 (and vice versa) (Wang et al.,
2000). CCR10 is expressed in some T cell and B cell
lines, but not in normal B cells. This suggests that
normal B cells may respond to CCL28 under certain
circumstances, but not in the resting state.
general by epithelial cells elsewhere including salivary
gland, trachea, and mammary epithelium.
IN THERAPY
Preclinical ± How does it affect
disease models in animals?
IN VITRO ACTIVITIES
No studies have been reported.
In vitro findings
Effects of therapy: Cytokine,
antibody to cytokine inhibitors, etc.
Recombinant human CCL28 attracts resting CD4
and CD8 T cells.
Bioassays used
Transwell chemotaxis assay.
IN VIVO BIOLOGICAL
ACTIVITIES OF LIGANDS IN
ANIMAL MODELS
Normal physiological roles
Possibly chemoattracts resting CD4 and CD8 T cells
and certain activated B cells.
Species differences
Because the human and mouse forms of CCL28 share
a high degree of homology and have comparable
expression patterns, similar biological activities are
expected.
PATHOPHYSIOLOGICAL ROLES
IN NORMAL HUMANS AND
DISEASE STATES AND
DIAGNOSTIC UTILITY
Normal levels and effects
Human and mouse CCL28 is highly expressed in
normal and pathological tissues of the colon and in
3
No studies have been reported.
References
Homey, B., Wang, W., Soto, H., Buchanan, M. E., Wiesenborn,
A., Catron, D., Muller, A., McClanahan, T. K., Dieu-Nosjean,
M. C., Orozco, R., Ruzicka, T., Lehmann, P., Oldham, E., and
Zlotnik, A. (2000). Cutting edge: the orphan chemokine receptor G protein-coupled receptor-2 (GPR-2, CCR10) binds the
skin-associated
chemokine
CCL27
(CCL27/ALP/ILC).
J. Immunol. 164, 3465±3470.
Jarmin, D. I., Rits, M., Bota, D., Gerard, N. P., Graham, G. J.,
Clark-Lewis, I., and Gerard, C. (2000). Cutting edge: identification of the orphan receptor G-protein-coupled receptor 2 as
CCR10, a specific receptor for the chemokine ESkine.
J. Immunol. 164, 3460±3464.
Pan, J., Kunkel, E. J., Gosslar, U., Lazarus, N. I., Langdon, P.,
Broadwell, K., Vierra, M. A., Genovese, M. C., Butcher, E. C.,
and Soler, D. (2000). A novel chemokine ligand for CCR10
and CCR3 expressed by epithelial cells in mucosal tissues.
J. Immunol. 165, 2943±2949.
Wang, W., Soto, H., Oldham, E. R., Buchanan, M. E., Homey, B.,
Catron, D., Jenkins, N., Copeland, N. G., Gilbert, D. J.,
Nguyen, N., Abrams, J., Kershenovich, D., Smith, K.,
McClanahan, T., Vicari, A. P., and Zlotnik, A. (2000).
Identification of a novel chemokine (CCL28), which binds to
CCR10 (GPR2). J. Biol. Chem. 275, 22313±22323.
Zlotnik, A., and Yoshie, O. (2000). Chemokines: a new classification system and their role in immunity. Immunity 12, 121±127.
Документ
Категория
Без категории
Просмотров
3
Размер файла
78 Кб
Теги
catron, pdf, zlotnik, ccl28, 2001, 6135
1/--страниц
Пожаловаться на содержимое документа