Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 87

cytoskeleton via actin-binding proteins on the other [ 164 ]. 61 Binding of the
GPIb-GP9 heterodimer to von Willebrand factor exposed in the subendothelium
enables platelet adhesion at sites of injury. In addition, platelet GP5 has a high-
affinity binding for thrombin.
Both thrombin and ADP activate platelets, which then secrete ADP, platelet-
derived growth factor, and fibrinogen from storage granules, as well as

thromboxane-A2 by immediate synthesis.
Platelet α 2B β 3 -integrin 62 binds to fibrinogen, leading to platelet aggregation.

With the simultaneous formation of a fibrin mesh, this process lead to the formation
of a platelet thrombus.

3.6.5 Non-Genomic Function of Transcription Factors

Transcription factors in platelets can have non-genomic functions. Platelets possess
ligand-regulated transcription factors peroxisome proliferator-activated receptor-
β

γ

(or nuclear receptors NR1c2 and NR1c3) and their binding partner
retinoid X receptor-

and -

α β

(or nuclear receptors NR2b1 and NR2b2), as well
as glucocorticoid receptor (or nuclear receptor NR3c1) [ 165 ]. The RXR ligands
prevent platelet aggregation and thromboxane-A2 release on Gq activation triggered
by ADP and TxA2 receptors. Nuclear receptors of the RXR category binds to
Gq subunit of G protein, thereby hindering Gq-induced Rac activation and calcium
release.
Factor PPAR

and -

γ

reduce platelet release of mediators such as tumor-necrosis factor
superfamily member TNFSF5, in addition to thromboxane-A2 [ 166 ]. Moreover,
collagen-stimulated platelet aggregation is attenuated by PPAR

γ

via inhibition of

γ

the collagen receptor GP6 [ 167 ]. Ligands of PPAR precludes phosphorylation of

components of the GP6 signaling pathway. Factor PPAR

γ

links to SYK kinase
that phosphoryles Linker for activation of T cells after platelet activation. This
association is impeded by PPAR

γ

agonists.

61 Density of glycoproteins on the platelet plasma membrane depends on: (1) reversible,
cytoskeletal-mediated translocation to the surface-connected canalicular system (SCCS), using
neutrophil cathepsin-G, thrombin receptor-activating peptide (TRAP], a synthetic molecule that
corresponds to the liberated N-terminal tail of the cleaved moderate-affinity thrombin receptor, or
a combination of adenosine diphosphate and adrenaline; and (2) proteolysis [ 164 ]. Glycoprotein
GP1b is processed by neutrophil cathepsin-G, neutrophil elastase, and calcium-dependent

peptidase; GP9 by thrombin and cathepsin-G; GP5 by thrombin, neutrophil elastase, and calcium-
dependent peptidase [ 164 ]. The Bernard-Soulier syndrome is an autosomal recessive disorder
characterized by thrombocytopenia, giant platelets, and a bleeding tendency. It results from
abnormalities of the GP1b-GP5-GP9 complex, especially mutations of the GP1BA, GP1BB, and
Gp9 genes.
62 A.k.a. glycoproteic GP2b-GP3a dimer.

α