Biology Reference
In-Depth Information
part of the innate immune, as well as the adaptive immune, response. Com-
plement fragments bind to specific receptors to induce cellular responses that
trigger inflammatory and immune responses.
b
-Arrestins 1 and 2 are
involved in complement receptor C3aR desensitization, internalization,
degranulation, NF-
k
B activation, and chemokine generation in mast cells.
41
Stable knockdown of
b
-arrrestin 2 expression attenuated C3aR desensitiza-
tion, internalization, and NF-
k
B activity, as well as chemokine generation in
human mast cell lines that endogenously express C3aR.
41
However, silenc-
ing
b
-arrestin 1 decreased C3a-induced mast cell degranulation, without
affecting C3aR desensitization. Knockdown of
b
-arrestin 1,
b
-arrestin 2,
or both enhanced the early response to C3a but inhibited G protein-
dependent ERK1/2 phosphorylation.
41
Other studies suggested that
although C3aR interacts with
b
-arrestins, they do not appear to be involved
in C3a-induced ERK activation in a leukemia cell line.
42
Complement C5a
binds to the C5a receptor (C5aR), a GPCR, and the C5L2 receptor, a non-
GPCR, to elicit its proinflammatory functions. A recent study suggested that
C5a binding to C5aR recruits C5L2 and
b
-arrestin 2.
43
Activation of C5L2
results in the inhibition of C5aR-
b
-arrestin-mediated ERK1/2 activation,
with no apparent alteration of G protein-mediated functions such as calcium
influx and receptor endocytosis.
43
Bone marrow-derived macrophages
devoid of
b
-arrestin 2 showed decreased complement C1q gene expression
and enhanced factor-independent survival of CSF-1 through JNK/ERK
signaling.
44
Therefore,
b
-arrestins appear to regulate complement functions
through receptor desensitization as well as ERK signaling.
3.
b
-ARRESTINS IN ADAPTIVE IMMUNITY
3.1.
-Arrestins and lymphocytes
Both
b
-arrestins 1 and 2 are expressed in lymphocytes.
45
In thymocytes,
b
-arrestin 1 expression was very low compared with splenocytes or lympho-
cytes isolated from lymph nodes.
46
Compared with B cells, T cells contain
substantially more
b
-arrestin 2.
45
For both na
¨
ve and activated cells, CD4
þ
T cells had much more nuclear
b
-arrestin 1 than CD8
þ
T cells.
46
CD4
þ
T lymphocytes of mice with allergic asthma expressed higher levels of
b
-arrestin 2 at both the mRNA and protein levels compared with normal
mice.
47
b
b
-Arrestin expression levels are dependent upon cell type, activation
status, and disease states.
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