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role in CXCR2 signaling in neutrophils. Neutrophils isolated from perito-
neal cavity of
b
-arrestin 2-deficient mice show enhanced calcium mobiliza-
tion, superoxide anion production, and GTPase activity, but decreased
receptor internalization in CXCR2 signaling.
36
b
-Arrestin 2-deficient mice
also demonstrate increased recruitment of PMNs in response to CXCL1 in
the air pouch model and in excisional wound beds, leading to faster wound
reepithelialization.
36
2.3.
-Arrestins and natural killer cells
Natural killer (NK) cells constitute a major component of the innate
immune systemandplaya significant role in tumor rejectionandviral clearance.
NK cell receptors express activating NK receptors such as NKG2D and inhib-
itory receptors such as killer-cell immunoglobulin-like receptors.
b
-Arrestin 2
has been reported to interact with the inhibitory receptor KIR2DL1 and
mediate the binding of tyrosine phosphatases to KIR2DL1 to facilitate the
inhibitory signaling of NK cells.
37
A mutated KIR2DL1 with an arginine
residue at position 245 in its transmembrane domain recruited more
b
-arrestin
2 and Src-homology-2 domain-containing protein tyrosine phosphatase 2.
38
NK cells isolated from
b
-arrestin 2-deficient mice demonstrated higher
cytotoxicity thanWT mice, while NK cells from
b
-arrestin 2 transgenic mice
showed reduced cytotoxicity which could be restored by
b
-arrestin 2 knock-
down.
37
Thus,
b
-arrestin 2 is a negative regulator in NK cell cytotoxicity.
b
2.4.
-Arrestins and mast cells
Mast cells contain granules rich in histamine and heparin, and play a role in
allergy and anaphylaxis, as well as in tissue injury.
7
Mast cell degranulation
can be triggered by injury, cross-linking of Immunoglobulin E receptors,
and complement proteins.
7
In the intestine, mast cells release tryptase to acti-
vate PAR2 in colonocytes. PAR2 then associates with
b
-arrestins to activate
ERK1/2, which increases epithelial permeability by regulating the assembly
of perijunctional F-actin.
39
b
b
-Arrestins may play a role in the increased epi-
thelial permeability of the intestine during stress and inflammation through
the mediation of mast cell activation.
2.5.
-Arrestins and complement
The complement system contains more than 30 proteins, which regulate tis-
sue injury and inflammation.
40
The complement system can be activated as
b
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