PREFINAL LECTURE L1: PLATELET PRODUCTION, STRUCTURE AND FUCNTION Flashcards
(309 cards)
1
Q
T or F:
Platelets are nucleated blood cells
A
F
They are non-nucleated
2
Q
Average platelet count
A
150-400 x10^9/L
3
Q
T or F:
Platelets count is slightly higher in women than in men
A
T
4
Q
Platelet count is slightly lower in both sexes who are older than how many years of age
A
65 years
5
Q
When does platelet trigger primary hemostasis
A
Upon exposure to sub-endothelial collagen or endothelial cell inflammatory proteins
6
Q
Platelets arise from what bone marrow cells
A
Megakaryocytes
7
Q
Largest bone marrow blood cells
A
Megakaryocytes
8
Q
What do you call the characteristic of megakaryocytes wherein they posses multiple chromosome copies
A
Polyploid
9
Q
Size of megakaryocytes
A
30-50 um in diameter
10
Q
Observable morphology of megakaryocytes under Wright stain
A
Multilobulated nucleus, and abundant granular cytoplasm
11
Q
Megakaryocytes account for how many percent of all bone marrow cells
A
Less than 0.5%
12
Q
How many megakaryocytes on a normal Wright stained bone marrow aspirate smear may be identified
A
2-4 megakaryocytes per 10x LPF
13
Q
A specialized microenvironment near blood vessels (especially venous sinusoids) where stem cells and other cells interact.
A
vascular niche
14
Q
wide, thin-walled blood vessels in the bone marrow that help with blood cell movement into the bloodstream.
A
venous sinusoids
15
Q
What causes megakaryocytes and HSCs to cluster in vascular niches?
A
cytokines from stromal cells
16
Q
growth factor that recruits megakaryocyte progenitors
A
thrombopoietin (TPO)
17
Q
megakaryocyte progenitors are recruited from
A
common myeloid progenitors
18
Q
T or F:
Megakaryocytes can only be found in the bone marrow
A
F
can also be found in the lungs
19
Q
megakaryocyte progenitors arise from the common myeloid progenitor under the influence of what transcription gene product
A
GATA-1
20
Q
GATA-1 stands for
A
globin transcription factor-1
21
Q
GATA-1 is a protein product of what gene
A
X chromosome gene GATA1
22
Q
GATA-1 is regulated by what cofactor
A
FOG1
23
Q
FOG1 stands for
A
friend of GATA
24
Q
FOG1 is a product of what gene
A
zinc finger protein multitype 1 (ZFPM1) gene
25
megakaryocyte differentiation is suppressed by what transcription gene product
MYB
26
purpose of GATA-1 and MYB
balance megakaryocytopoiesis with erythropoiesis
27
how many megakaryocyte lineage-committed progenitor stages are there
3
28
enumerate the stages in order of differentiation
1) burst-forming unit (BFU-Meg)
2) colony-forming unit (CFU-Meg)
3) light density CFU (LD-CFU-Meg)
29
all three progenitor stages resemble what cell
lymphocytes
30
T or F:
the three progenitor stages can be distinguished by Wright-stained light microscopy
F
31
progenitor stage/s that are diploid and undergo normal mitosis
1) BFU-Meg
2) CFU-Meg
32
how many colonies can BFU-Meg form in culture
hundreds
33
how many colonies can CFU-Meg form in culture
dozens
34
progenitor stage/s that undergo endomitosis
LD-CFU-Meg
35
what makes endomitosis unique to megakaryocytes
DNA replication and cytoplasmic maturation are normal but cells lose their capacity to divide
36
3 factors that stimulate megakaryocyte formation from hematopoietic stem cells
1) TPO
2) Meg-CSF
3) IL-3
37
endomitosis is a form of mitosis that lacks what cell division processes
telophase and cytokinesis
38
what happens in cytokinesis
separation into daughter cells
39
As GATA-1 and FOG1-driven transcription slows, what transcription factor mediates the switch from mitosis to endomitosis
RUNX1
40
how does RUNX1 mediates the switch from mitosis to endomitosis
by suppressing the Rho/ROCK signaling pathway
41
what happens in reduced Rho/ROCK signal
actin and myosin levels will be inadequate
42
what happens if actin and myosin levels are inadequate
cytokinesis will fail
43
what transcription factor promotes DNA replication without cell division (endomitosis)
NF-E2
44
What does it mean for a cell to be polyploid (e.g., 8N, 16N, 32N)?
A polyploid cell has multiple complete sets of chromosomes
| For example, 8N means the cell has four times the normal 2N DNA content
45
what does 128N indicate
this level of ploidy is unusual, and may signal hematologic disease
46
T or F:
some megakaryocytes reach 128N
T
47
purpose of employing multiple DNA copies of megakaryocytes
to synthesize abundant cytoplasm
48
phase in which microscopists become able to recognize the unique Wright-stained morphology of megakaryocytes
terminal differentiation
49
least differentiated megakaryocyte precursor
MK-1 stage
50
MK-1 is aka
megakaryoblast
51
T or F:
megakaryoblast look like lymphocytes
F
they no longer do
52
megakaryoblasts are not reliably distinguishable with what cells
bone marrow myeloblasts
53
Vague clues that help distinguish megakaryoblasts
1) plasma membrane blebs
2) blunt projections from the margin
54
the megakaryoblast begins to develop most of what cytoplasmic ultrastructures
1) procoagulant-laden-α-granules
2) dense granules
3) demarcation system (DMS)
55
series of membrane-lined channels that invade from the plasma membrane and grown inward to subdivide the entire cytoplasm
DMS
56
DMS is biologically identical to what
megakaryocyte's plasma membrane
57
what does DMS do during thrombocytopoiesis
delineates the individual platelets
58
developmental stage of megakaryocyte where the nucleus begins to indent and the cell has 4N DNA content
MK-II stage
59
MK-II is aka
promegakaryocyte
60
when does the promegakaryocyte reaches its full ploidy level
by the end of MK-II stage
61
most abundant megakaryocyte stage
MK-III
62
MK-III is aka
megakaryocyte
63
describe the morphology of megakaryocytes (nucleus, chromatin, cytoplasm)
1) nucleus is intensely dented/lobulated
2) variably condensed chromatin with light and dark patches
3) azurophilic and granular cytoplasm
64
platelet shedding is aka
thrombocytopoiesis
65
what makes megakaryocytes "platelet-like"
because of the spread of the DMS and α-granules
66
during thrombocytopoiesis, a single megakaryocyte may shed how many platelets
2000-4000 platelets
67
in an average size healthy human there are how many megakaryocytes, producing how many platelets per day
10 megakaryocytes producing 10 platelets per day
68
total platelet population turn over
8 to 9 days
69
at what instances where platelet production may rise by as much as tenfold
increased platelet consumption e.g. immune thrombocytopenic purpura
70
evidence of platelet budding or shedding in megakaryocyte cultures
1) DMS dilates
2) longitudinal bundles of tubules form
3) proplatelet process develop
4) transverse constrictions appear throughout the proplatelet process
71
how does proplatelet process shed platelets
they pierce through or between sinusoid-lining endothelial cells and extend to the venous blood
72
thrombocytopoiesis leaves behind naked megakaryocyte nuclei to be consumed by
marrow macrophages
73
what methods are used to identify visually indistinguishable megakaryocyte progenitors in hematologic disease
1) immunostaining of fixed tissue
2) flow cytometry with immunologic probes
3) FISH with genetic probes
74
what are the megakaryocyte membrane markers
1) MPL
2) CD34
3) CD41
4) CD61
5) CD36
6) CD42
7) CD62
75
MPL stands for
myeloproliferative leukemia protein
76
what is MPL
TPO receptor site
77
T or F:
MPL is present at all maturation stages
T
78
CD34 is aka
stem cell and myeloid progenitor marker
79
T or F:
CD34 disappears as differentiation proceeds
T
80
marker that first appears in megakaryocyte progenitors
CD41/CD61
81
CD41/CD61 is aka
glycoprotein (GP) IIb/IIIa
82
T or F:
CD41/CD61 remains present throughout maturation
T
83
proteins that may be detected in the fully developed megakaryocyte
1) cytoplasmic coagulation factor VIII
2) VWF
3) fibrinogen
84
weight of TPO
70,000 Dalton
85
TPO possesses how many percent homology with erythropoietin
23%
86
mRNA for TPO has been found in what organs
kidney, liver, stromal cells, and smooth muscle cells
87
primary source of TPO
liver
88
T or F:
TPO is a hormone
T
circulates as a hormone in the plasma
89
aside from being a hormone, TPO is also a
ligand
90
how does TPO function as a ligand
binds the megakaryocyte and MPL
91
define v-mpl
viral oncogene associated with murine myeloproliferative leukemia
92
T or F:
The plasma concentration of TPO is directly proportional to platelet and megakaryocyte mass
F
inversely proportional
93
induces thrombocytopoiesis
TPO
94
elevate the platelet count in patients being treated for a variety of cancers, including acute leukemia
Synthetic TPO mimetics (analogs)
95
a non immunogenic oligopeptide that raises the platelet count in patients with chronic immune thrombocytopenic purpura (ITP)
romiplostim (Nplate, Amgen)
96
nonpeptide TPO mimetic that binds an MPL site separate from romiplostim and is used in the treatment of chronic ITP and patients with thrombocytopenia resulting from chronic hepatitis C or severe aplastic anemia
eltrombopag (Promacta, Novartis)
97
cytokines that function with TPO to stimulate megakaryocytopoiesis
IL-3
IL-6
IL-11
98
interleukin that acts in synergy with TPO to induce early differentiation of stem cells
IL-3
99
interleukins that act in presence of TPO to enhance endomitosis, megakaryocyte maturation, and thrombocytopoiesis
IL-6
IL-11
100
IL-11 mimetic that stimulates platelet production in patients with chemotherapy-induced thrombocytopenia
oprelvekin (Neumega, Pfizer)
101
cytokines and hormones that participate with TPO and interleukins
1) stem cell factor
2) GM-CSF
3) G-CSF
4) acetylcholinesterase-derived megakaryocyte growth stimulating peptide
102
stem cell factor is aka
kit ligand, mast cell factor
103
factors that inhibit in vitro megakaryocyte growth
1) Platelet factor 4 (PF4)
2) B-thromboglobulin
3) neutrophil-activating peptide 2
4) IL-8
104
reduction of these transcription factors diminish megakaryocytpoiesis at the progenitor, endomitotic, and terminal maturation phases
1) FOG1
2) GATA-1
3) NF-E2
105
platelets are distributed throughout the RBC monolayer at (value)
7-21 cells per 100 x field
105
size of platelets
2.5 um in diameter
106
the mean platelet volume is measured in
buffered isotonic suspension
107
normal MPV
8-10 fL
108
shape of circulating resting platelet
biconvex
109
shape of platelets in EDTA blood
round-up
110
average platelet count of men over 65
122-350 x 10^9/L
111
average platelet count of women over 65
140-379 x 10^9/L
112
proportion of platelets sequestered within the spleen
one third
113
appear in compensation for thrombocytopenia
reticulated platelets
114
reticulated platelets are aka
stress platelets
115
size of reticulated platelets
>6 um
116
MPV of reticulated platelets
12-14 fL
117
shape of reticulated platelets in citrated tubes
cylindrical and beaded
118
how can platelet dense granule nucleotides interfere with the quantitative evaluation of reticulated platelet production
falsely raising by binding nucleic acid dyes
119
T or F:
reticulated platelets are potentially prothrombic
T
120
neutral phospholipids of plt plasma membrane that predominate the outer blood plasma layer
phosphatidylcholine
sphyngomyelin
121
anionic or polar phospholipids that predominate in the inner, cytoplasmic layer
phosphatidylinositol
phosphatidylethanolamine
phosphatidylserine
122
how can phosphatidylinositol support platelet activation
by supplying arachidonic acid
123
arachidonic acid becomes converted to
thromboxane A2
124
cellular and humoral stimuli that activates receptors
ligands or agonists
125
platelet membrane surface
glycocalyx
126
glycocalyx absorbs what substances
albumin, fibrinogen and other plasma proteins
127
glycocalyx absorbs plasma proteins and transports them to internal storage organelles with the use of what process
endocytosis
128
formed when the plasma membrane invades the platelet interior
surface-connected canalicular system (SCCS)
129
upon platelet activation, the SCCS is the route for
endocytosis and secretion of a-granule contents
130
condensed remnant of the rough endoplasmic reticulum
dense tubular system (DTS)
131
the DTS sequesters what molecules and enzymes that support platelet activation
1) calcium
2) phospholipase A2
3) cyclooxygenase
4) thromboxane A2
5) phospholipase C
6) inositol triphosphate (IP3)
7) diacylglycerol (DAG)
132
which enzyme/s support the production of thromboxane A2
1) PLA2
2) COX-1/2
3) thromboxane synthetase
133
which enzyme/s support the production of IP3 and DAG
phospholipase C
134
what maintains the platelet's discoid shape
circumferential microtubules
135
tubules disassemble at refrigerator temp or when platelets are treated with
colchicine
136
shape of platelets when the tubules disassemble
round
137
platelets shape at 37C
disc shape
138
meshwork composed of actin
microfilaments
139
function of actin
contractile in platelets and anchors the plasma membrane glycoproteins and proteoglycans
140
actin appearance in the resting platelet
globular and amorphous
141
actin appearance when the cytoplasmic calcium concentration rises
filamentous and contractile
142
the cytoplasm contains intermediate filaments of
desmin and vimentin
143
how does the intermediate filaments contribute in maintaining the platelet shape
connect actin and the tubules
144
what control the plt shape change, extension of pseudopods, and secretion of granule contents
1) microtubules
2) actin microfilaments
3) intermediate microfilaments
145
dense granules and α-granules share some of the same key membrane proteins, such as:
P-selectin
αIIbβ3 (aka GPIIb/IIIa)
GPIb/IX/V complex
146
there are how many a-granules in each platelet
50-80
147
color of a-granules in osmium-dye transmission electron microscopy preparations
medium gray
148
a-granules contain what substances
proteins
149
as the platelet becomes activated, a-granule membranes fuse with
SCCS
150
what happens to a-granules during platelet activation
flow to the microenvironment and participate in plt adhesion and aggregation and support plasma coagulation
151
how many dense granules per platelet
2-7
152
T or F:
dense granules appear later than a-granules in megakaryocyte differentiation
T
153
color of dense granules under osmium
black (opaque)
154
what happens to dense-granules during platelet activation
migrate to the plasma membrane and release their contents directly into the plasma on platelet activation
155
aside from proteins, platelets also contain what substance similar to neutrophils
lysosomes
156
what are the platelet dense granules
1) calcium and magnesium
2) ATP
3) ADP
4) serotonin
157
property of ADP
supports neighboring platelet aggregation by binding to P2Y1 and P2Y12 ADP receptors
158
property of serotonin
vasoconstrictor that binds endothelial cells and platelet membrane
159
property of calcium and magnesium
support platelet activation and coagulation
160
platelet membrane contains what receptors
1) Cell adhesion molecule (CAM) integrin family
2) seven-transmembrane receptor family
3) miscellaneous receptors
161
purpose of integrins
allows platelet to adhere to the injured blood vessel lining by binding collagen
162
what does integrin being heterodimeric mean
it composed of two dissimilar proteins
163
an integrin that binds the subendothelial collagen that becomes exposed in the damaged blood vessel wall
GP Ia/IIa
164
Which integrin binds to laminin?
α6β1
165
which integrin binds to fibronectin
α5β1
166
What platelet receptors promote adhesion by binding to endothelial proteins?
α5β1 and α6β1
167
It binds to collagen and the adhesive protein thrombospondin.
GP IV
168
What is GP Ib/IX/V composed of?
-Two GP Ibα
-two GP Ibβ
-two GP IX
-one GP V subunit
169
What is the function of GP Ib/IX/V under high shear conditions?
binds to von Willebrand factor (vWF), and support platelet tethering for capillaries and arterioles
170
What is the role of GP Ibβ in platelet signaling?
interacts with actin-binding protein, enabling “outside-in” signaling
171
What do GP IX and GP V contribute to the GP Ib/IX/V complex?
help assemble the four GP Ib molecules
172
Where are the integrin αIIbβ3 (GP IIb/IIIa) found in resting platelets?
1) plasma membrane
2) SCCS
3) a-granule membranes
173
What activates the integrin αIIbβ3 to bind fibrinogen?
Inside-out signaling triggered by agonist
174
Why is αIIbβ3 essential in platelet aggregation?
It binds fibrinogen, forming bridges between platelets, leading to aggregation.
175
Besides fibrinogen, which proteins bind to αIIbβ3
vWF, vitronectin, and fibronectin
176
amino acid sequence of the adhesive proteins as well as fibrinogen
arginine-glycine-aspartate (RGD)
177
what are the agonists for seven-transmembrane repeat receptors (STRs)
1) Thrombin
2) Thrombin receptor activation peptide (TRAP)
3) adenosine diphosphate (ADP)
4) epinephrine
5) serotonin
6) thromboxane A2
178
STR of thrombin
PAR1 and PAR4
179
STR of ADP
P2Y1 and P2Y12
180
STR of TXA2
TPa and TPb
181
STR of epinephrine
a2-adrenergic
182
STR of prostacyclin
IP
183
effect of P2Y1 signaling
-increase in intracellular Ca levels
-contributes to initial platelet activation
-shape change
-formation of small REVERSIBLE aggregates
184
effect of P2Y12 signaling
-decrease in cyclic adenosine monophosphate (cAMP) levels
-formation of IRREVERSIBLE platelet aggregates
185
what happens during binding of TPa and TPb to TXA2
produce more TXA2 from the platelet that activates neighboring platelets (recruiting)
186
what happens during binding of epinephrine and a2-adrenergic receptor
-inhibits adenylate cyclase
-reduction in cAMP
187
prostacyclin is a prostaglandin produced by what cells
endothelial cells
188
what happens during binding of prostacyclin with IP receptor
-increase cAMP
-inhibition of platelet activation
189
IP means
inositol phosphate
190
what are the intercellular adhesion molecules (ICAMs)
CD50
CD54
CD102
191
ICAMs function
play a role in inflammation and immune reaction
192
what mediates platelet-to-white- blood cell and platelet-to-endothelial cell adhesion
platelet-endothelial cell adhesion molecule (PECAM)
193
marker of PECAM
CD31
194
a low affinity receptor for the immunoglobulin Fc portion that plays a role in heparin-induced thrombocytopenia
FcyIIA
195
marker for FcyIIA
CD32
196
integrin that facilitates platelet binding to endothelial cells, leukocytes
P-selectin
197
marker for P-selectin
CD62
198
where is CD62 found
a-granule membranes of the resting platelet
199
where does CD62 migrate
via SCCS to the surface of activated platelets
200
common means for measuring in vivo platelet activation
P-selectin quantification thru flow cytometry
201
T or F:
platelet adhesion, aggregation and secretion often occur simultaneously
T
202
what is shear force
stress created in vessel walls as blood flows
203
shear force in venules and veins
500 s-1
204
shear force in arterioles and capillaries
5000 s-1
205
shear force in stenosed arteries
up to 40,000 s-1
206
in shear force that exceed 1000 s-1, platelet adhesion and aggregation require as define sequence of events which involves what key players
1) collagen
2) tissue factor
3) phospholipid
4) VWF
5) CAMS, ligands, activators
207
what happens when blood vessel wall is injured
1. disrupts the collagen of the ECM
2. damaged endothelial cells release vwf and adhere to sites of injury
208
molecular weight of vwf
500,000 to 20,000,000 Daltons
209
what happens to WVF under shear stress
It becomes thread-like and unrolls, exposing sites for weak binding to GP Ibα.
210
Which platelet receptor component binds to VWF during shear stress?
GP Ibα, a part of the GP Ib/IX/V complex.
211
What is the function of the reversible binding between VWF and GP Ibα?
It tethers and decelerates the platelet's forward motion.
212
Which enzyme regulates the interaction between VWF and platelets?
ADAMTS13.
213
ADAMTS13 is aka
VWF-cleaving protease
214
What does ADAMTS13 do to VWF?
cleaves large VWF multimers into smaller, less active forms
215
secretes ADAMTS13
liver
216
what disrupts the temporary VWF-GPIba tethering reaction
GPVI comes in contact with the exposed ECM collagen
217
What happens when type I fibrillar collagen binds to GP VI on the platelet?
triggers internal platelet activation pathways, releasing TXA2 and ADP in an "outside-in" reaction
218
receptors involved in the "outside-in" reaction
TPa and TPb for TXA2
P2Y1 and P2Y12 for ADP
219
What does the "inside-out" reaction triggered by TXA2 and ADP lead to?
raises the affinity of integrin α2β1 for collagen
220
What is the combined effect of GP Ib/IX/V, GP VI, and α2β1 integrin on the platelet?
platelet become firmly affixed to the damaged surface
221
What happens to the platelet after it is firmly affixed to the damaged surface?
It loses its discoid shape and spreads.
222
What is exposed on the blood vessel wall after injury, in addition to collagen and VWF?
Tissue factor
223
tissue factor is from
subendothelial smooth muscle cells and fibroblasts
224
tissue factor triggers the production of
thrombin
225
How does thrombin activate platelets?
it cleaves PAR1 and PAR4
226
the further activation caused by thrombin generates what
collagen and thrombin activated (COAT) platelet
227
role of TXA2 and ADP in platelet activation
activate neighboring platelets, triggering inside-out activation of integrin αIIbβ3
228
What does the inside-out activation of integrin αIIbβ3 enable?
enables integrin αIIbβ3 to bind RGD sequences of fibrinogen and VWF
229
What does P-selectin from the α-granule membranes promote?
promotes the binding of platelets with leukocytes
230
What happens to platelets upon further activation and aggregation in terms of its shape
discoid to round, form pseudopods
231
Why do platelets form a syncytium during aggregation?
Because platelets exhaust their internal energy sources and membrane integrity is lost
232
what occurs during lost of membrane integrity of platelets during aggregation
phosphatidylserine flip to the outer layer
233
what is synyctium
massive clump of platelets
234
in primary hemostasis, arteries may end with the formation of what
white clot
235
white clot is primarily composed of
plt and vwf
236
what does white clot indicate (pathologic)
inappropriate plt activation ; pathologic basis for arterial thrombotic events
237
examples of arterial thrombotic events
1) AMI
2) peripheral artery dse
3) ischemic stroke
238
why does avidity of a2b1 and GPVI receptors increase risk of cardiovascular events
high avidity-> more binding sites for collagen and vwf-> inc plt adhesion/aggregation-> inc risk of abnormal clotting
239
secondary hemostasis is
coagulation
240
What combination of factors triggers secondary hemostasis
1) polar phospholipid exposure on activated plt
2) plt fragmentation with cellular microparticle release
3) secretion of a-granules and dense granules
241
primary hemostasis: white clot; secondary hemostasis: ?
red clot
242
red clot is composed of
fibrin and rbcs
243
role of red clot
essential in wound repair
244
white clot: inappropriate coagulation in arteries; red clot: ?
inappropriate coagulation in veins and venules
245
pathologic indications of red clot
deep vein thrombosis and pulmonary embolism
246
triggers the actin microfilament contraction in platelets
-outside in activation of plt through STR (ADP+P2Y12)
-GPVI
247
what happens when intermediate filaments contract
moves the circumferential microtubules inward-> compressing the granules
248
Where do the contents of the a-granules and lysosomes flow after platelet activation?
SCCS
249
Where does dense granules migrate and secrete their contents
plasma membrane
250
dense granules secrete
vasoconstrictors and platelet agonists
251
what does vasoconstrictors and platelet agonists do
amplify primary hemostasis
252
role of a-granule contents in platelet activation
large molecule coagulation proteins that participate in secondary hemostasis
253
How do platelets support coagulation at the cellular level?
by presenting phosphatidylserine, where complexes assemble
254
what complexes assemble at the phosphatidylserine
factor IX/VIII (tenase) and factor X/V (prothrombinase) complexes
255
role of calcium in platelet-mediated coagulation
secreted by dense granules, helps form tenase and prothrombinase complexes.
256
contents of a-granules
1) fibrinogen
2) factor V
3) factor VIII
4) VWF
257
role of a-granules
supports the action of tenase and prothrombinase
258
all a-granule proteins
1) platelet-derived growth factor
2) endothelial growth factor
3) transforming growth factor B
4) fibronectin
5) thrombospondin
6) platelet factor 4
7) B-thromboglobulin
8) plasminogen
9) plasminogen activator inhibitor-1
10) a2-Antiplasmin
11) protein C inhibitor
259
a-granule protein:
supports mitosis of fibroblasts and smooth muscle cells
1) platelet-derived growth factor
2) endothelial growth factor
3) transforming growth factor-B
260
a-granule protein:
adhesion molecule
1) fibronectin
2) thrombospondin
261
a-granule protein:
heparin neutralization, suppresses megakaryocytopoiesis
platelet factor 4
262
a-granule protein:
only found in platelet a-granules
B-thromboglobulin
263
a-granule protein:
fibrinolysis promotion
plasminogen
264
a-granule protein:
fibrinolysis control
1) plasminogen activator inhibitor-1
2) a2-Antiplasmin
265
a-granule protein:
coagulation control
protein C inhibitor
266
What triggers the formation of platelet microparticles?
triggered by an activating stimulus that increases the intracellular calcium concentration in platelets
267
How do elevated calcium levels inside platelets contribute to microparticle formation?
1. inhibits asymmetric distribution of phospholipids
2. activates enzyme calpain
268
what does caplain do
cleaves platelet cytoskeleton
269
inhibition of asymmetric distribution of phospholipids and caplain leads to
outward blebbing of the plasma membrane and formation of plt microparticles
270
most abundant microparticles in the circulation
plt microparticles
271
plt microparticles are formed after
exposure of plt to strong agonists or shear stress
272
How do platelet microparticles influence coagulation?
exposing phosphatidylserine on their surface, crucial for the assembly of tenase and prothrombinase
273
other functions of plt microparticles aside coagulation
1) modulate inflammation
2) oxidative stress
3) angiogenesis
4) thrombosis
274
elevated plt particles is significant in what conditions
hypercoagulable conditions
275
G-proteins are made up of what subunits
a, B, y (heterotrimers)
276
What happens to G-proteins when an agonist binds to a receptor?
The G-protein releases GDP and binds GTP, activating the G-protein.
277
What does the activated Gα subunit do?
briefly separates from the complex (G-protein), acts like an enzyme to hydrolyze GTP to GDP, and triggers signaling pathways
278
What are two major signaling pathways triggered by G-protein activation?
Eicosanoid synthesis and the IP3-DAG pathway.
279
how does hydrolysis done by G-protein leads to activation of pathways
hydrolysis resulted to phosphorylation
280
eicosanoid synthesis is aka
prostaglandin, cyclooxygenase, or thromboxane pathway
281
What enzyme releases arachidonic acid from the membrane?
Phospholipase A2
282
5,8,11,14-eicosatetraenoic acid is aka
arachidonic acid
283
arachidonic acid is the substrate for
cyclooxygenase
284
what does cyclooxygenase do
converts arachidonic acid to prostaglandin G2 and prostaglandin H2
285
enzyme that acts on prostaglandin H2 to produce TXA2
thromboxane synthetase
286
what happens when TXA2 binds membrane receptors TPa or TPb
1. inhibits adenylate cyclase activity
2. reducing cAMP concentrations, which mobilizes ionic
calcium from the DTS
287
what does the rising cytoplasmic calcium level cause
contraction of actin microfilaments producing platelet shape change and further platelet activation
288
What enzyme do endothelial cells use in place of thromboxane synthetase in the cyclooxygenase pathway?
prostacyclin synthetase
289
end product of the cyclooxygenase pathway in endothelial cells
prostaglandin I2 (PGI2)
290
prostaglandin I2 (PGI2) is aka
prostacyclin
291
what pathway does prostacyclin+IP receptor binding activate
IP3-DAG pathway
292
effect of prostacyclin on adenylate cyclase and cAMP
accelerates adenylate cyclase-> increased cAMP
293
prostacyclin effect on intracellular Ca levels
causes sequestration of ionic calcium to the dense tubular system (DTS), making calcium unavailable in the cytoplasm
294
what does the unavailability of Ca in the cytoplasm do to platelet function
shuts down plt function
295
endothelial cell eicosanoid pathway: suppress platelet activation; platelet eicosanoid pathway:
promotes plt activation
296
half-life of TXA2
30 seconds
297
TXA2 diffuses from the platelet and reduced to
thromboxane B2
298
What stable metabolite of thromboxane B2 is measurable in urine?
11-dehydrothromboxane B2
299
enzyme that initiates the IP3-DAG pathway in platelets
phospholipase C
300
What does phospholipase C do in the IP3-DAG pathway?
cleaves PIP2 to IP3 and DAG
301
function of IP3 in plt activation
releases calcium from the dense tubular system (DTS)
302
the release of Ca by IP3 causes what
actin microfilament contraction; activation of phospholipase A2
303
function of DAG in the IP3-DAG pathway
activates phosphokinase C
304
activation of phosphokinase C by DAG triggers the phosphorylation of what protein
pleckstrin
305
what does pleckstrin do
regulates actin microfilament contraction
306
Despite lacking nuclei, what allows platelets to synthesize proteins?
1) ribosomes
2) polyribosome complexes
3) regulatory factors
4) microRNAs (miRNAs)
5) template mRNAs
307
What triggers protein synthesis in platelets?
1. platelet activation
2. ligand binding to the GPIIb/IIIa receptor
308
What is the significance of platelet protein synthesis?
to alter their phenotype depending on level of activation
