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Chemokines Are A Group of Small Peptides That by
Chemokines Are A Group of Small Peptides That by
definition initiate the migration of effector cells. more than 50 chemokines and 18 chemokine receptors have
been identified. Chemokines bind to several receptors as
well as several receptors binding to several ligands [1, 2].
SDF-1is a member of the CXC chemokine family, and
has been shown to be essential for chemotaxis of both
progenitor and mature blood cells, and is involved in Blymphopoiesis
and myelopoiesis. It binds to the CXCR4
receptor, also known as CD184, which belongs to the class
of G-protein coupled receptors, whereby chemokine binding
will initiate the migration of lymphocytes [3], hematopoietic
stem cells [4, 5], and tumor cells [6-8]. A recent study of
Balabanian and colleagues indicated that SDF-1also binds
to and signals through the orphan receptor RDC1 in Tlymphocytes
[9].
SDF-1was isolated originally from a murine bonemarrow
stromal cell line, and was reported to function as a
pre-B-cell growth factor [10]. At present three SDF-1
isoforms, SDF-1, SDF-1, and SDF-1, are known. SDF1and SDF-1are encoded by a single gene, and are
generated by alternative splicing [11]. SDF-1(93 amino
acids) has an additional 4 amino acids at the C-terminal end,
whereby SDF-1is made up of 89 amino acids. Sequence
alignment analyses have revealed that SDF-1is highly
conserved between species. For instance, murine SDF-1
and SDF-1sequences are more than 92% identical to those
of human origin [11]. The SDF-1 gene was mapped to
chromosome 10q, in contrast to other members of the
intercrine family, which are localized on chromosome 4q and
17q.
It has thus been hypothesized that SDF-1may have
important functions distinct from those of the other
members of the intercrine family [11]. The third known isoform, SDF-1, was originally
isolated from the rat [12]. Compared to mice and humans in
which SDF-1/is expressed ubiquitously [11],
Gleichmann and colleagues found that neurons and Schwann
cells are the main regions of both SDF-1and SDF-1
mRNA expression in the rat [12]. SDF-1is the predominant isoform in embryonic and early postnatal rat
nerve tissue, whereas SDF-1is expressed at higher levels
in adulthood. In bone marrow, SDF-1availability has been shown to
be regulated by the uptake of SDF-1via CXCR4
expressing cells, which then translocate the chemokine into
the bone marrow. This transporter function is characteristic
of both endothelial and stromal cells