Biology Reference
In-Depth Information
6.1.2 Streptococcus pneumoniae
b
-Arrestin 1 has been reported to be involved in pneumococcal infection.
A report showed that upon infection with
S. pneumoniae
,
b
-arrestin 1 moved
to the plasma membrane of endothelial cells.
67
Pneumococcal invasion was
enhanced in a cell line by transfection of
b
-arrestin 1.
b
-Arrestin 1 was
shown to interact with the PAF receptor and contribute to successful infec-
tion by
S. pneumoniae
.
67
6.1.3 Polymicrobial sepsis
b
-Arrestin 2 protein expression was reduced in a murine model of CLP-
induced polymicrobial
sepsis.
134
b
-Arrestin-2-deficient mice exhibited
decreased mortality, increased IL-6 production, and elevated cecal
myeloperoxidase in a mouse model of polymicrobial sepsis by CLP.
Splenocytes devoid of
b
-arrestin 2 produced higher levels of TNF-
a
,
IL-6, and IL-10.
135
This is reminiscent of another study showing that
CLP-induced myeloperoxidase was
increased in
b
-arrestin-2-deficient
mouse lung.
34
b
-Arrestin 1 and
b
-arrestin-2-deficient mice were protected
from TLR4-mediated endotoxic shock and lethality.
112
These studies sug-
gest that
b
-arrestin 2 is a negative regulator in polymicrobial sepsis. There-
fore, treatment with flavocoxid preserved
b
-arrestin 2 expression and
reduced cytokine production, leading to protection against tissue damage
induced by CLP, presumably by decreasing myeloperoxidase activity in
the lung and the liver.
134
As chemokine receptors play key roles in pathogen recognition
and
b
-arrestins regulate chemokine receptor internalization, it is not
surprising that
b
-arrestins regulate chemokine receptor-mediated pathogen
clearance. For example, during
Staphylococcus aureus
associated lipoteichoic
acid induced pathogen recognition and monocyte migration,
b
-arrestins
mediate endocytosis of CCR5 into recycling endosomes, thus facilita-
ting the TLR2-negative regulation of CCR1, CCR2, and CCR5 on
monocytes.
122
6.1.4 Cryptococcal meningitis
b
-Arrestin 2 mRNA and protein levels were significantly elevated in periph-
eral blood mononuclear cells of patients with cryptococcal meningitis. The
increased
b
-arrestin 2 levels were concurrent with reduced cytotoxic activ-
ity against
Cryptococcus
, increased IL-10 levels, and reduced IFN-
g
expres-
sion in patient serum.
27
This study suggests that increasing IFN-
g
by the
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