|
|
|
Research: Selective Platelet Activaiton.
|
| |
|
Platelets in
Haemostasis
and Thrombosis.
|
|
 |
|
|
Platelets
are anuclear 3 - 4 μm cell fragments. They circulate in the blood in
the
resting (inactive, quiescent) state. They
become
activated, e.g., at the site of the wound, but also at atherosclerotic
plaques.
Activation entails a number of changes: exposure of phosphatidyl serine
(PS) ,
secretion of granules and the appearance of the granule markers CD62P
and CD63
on the platelet surface, change in the conformation of GPIIb/IIIa.
Activated platelets aggregate, adhere to the wound site, and catalyze
clotting
cascade reactions that culminate in the production of thrombin (the
catalyst is
PS).
Thrombin activates fibrinogen that polymerizes into fibrin, forming a
clot,
which seals the wound and stops the bleeding.
Platelet
activation at the site of atherosclerotic plaques leads to thrombus
formation
(thrombosis), vessel occlusion, heart attacks, and strokes.
|
|
| |
|
Other Functions
of Platelets
|
|
|
|
|
Recently,
multitude of new functions of platelets have been discovered.[Leslie M.
2010, Science328,
562] They play an important role in wound healing, inflammation, other
aspects of the innate immune responses as well as adaptive
immune response, angiogenesis, cancer metastasis,
etc.
In combination with
their haemostatic functions, this means that they also play a key role
in rejection or integration
of artificial implants.
Presumably, different
stimuli trigger different responses in platelets, leading to different
functions.
|
|
| |
|
Platelets appear
to be the "Swiss army knife" of host
defense reactions.
What are the
characteristics of
platelet response selectivity? How do different stimuli trigger
different responses? Can we exploit it to achieve specific, desired
response?
|
|
The
idea,
that platelet
responses to different stimuli are different is very attractive for the
design of new haemocompatible materials and better antiplatelet
therapies.
In my group, we study the process of platelet activation, both by
biomaterials (in the context of
biocompatibility) and by natural agonists (in the context of
physiological coagulation
and wound healing as well as pathological thrombosis).
We also develop new methods for detecting differences in platelets
activated by different stimuli.
Our goal is to understand the underlying molecular mechanisms and to
apply this knowledge towards the design of new materials, diagnostic
assays, and therapeutic options.
|
| |
| |
|
Selective platelet
activation by surfaces.
|
|
 |
|
|
The figure
above
shows that platelet activation profiles on the surface of a popular
biomaterial, TiO2, depend on whether Ca2+ is present or not.
In
solution, activated platelets can be distinguished from the resting
platelets by flow cytometry (left). For platelets adhering
at surfaces,
the same can be done by fluorecence microscopy (right). In
both cases,
platelets are labeled with antibodies against the various
markers.
Resting platelets do not
express PS, CD62P, or CD63. Activated
platelets in solution, platelets adsorbed on glass, or on TiO2 in the
presence of Ca2+, express all these markers. Platelets
adsorbed on
TiO2
in the absence of Ca2+ do not express CD62P.
Selectivity of platelet
activation is a topic of considerable current interest due to the
possible applications in implant integration, thrombosis and bleeding
therapies, and drug delivery protocols.
References:
Gupta and Reviakine, Biointerphases 2012.
S. Gupta
Selective Activation of Platelets by Surfaces and Soluble
Agonists. Ph.D. thesis, March 21st, 2014.
|
|
|
|
A new assay to
differentiate between platelets activated by different
agonists.
|
|
Coming soon!
|
|
|
