plaquetas fundamentos
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PLAQUETAS
PlaquetasPlaquetasMirta Schattner PhD
Laboratorio de Trombosis I
CONICET
Academia Nacional de Medicina
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Spontaneous proplatelet formation by
megakaryocytes in methylcellulose culture medium
Takahashi R et al. Blood 1999; 93: 1951-1958.
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Injuria Endotelial
Adhesión Plaquetaria
Componentes Subendoteliales
Agregación Plaquetaria
Formación del Trombo
Sustancias Vasoactivas
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Endotelio
FvWcolágeno
ADP
ON PGI2Ca2+ serotonina
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VII VII
fibrinógeno fibrina
FTFT FT
VII VIITR
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plasmina
plasmina
plasmina
plasminaplasmina
plasmina plasmina
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OXIDO NITRICO
SHEAR STRESS
INFECCION INTRACELULAR
INJURIA
TROMBINA
HIPOXIA
STRESS OXIDATIVO
CITOQUINAS
HORMONAS
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PLA2
Inside-out
Outside-in
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Morfología Plaquetaria
Gránulos alfa
Gránulos densos
Microtúbulos
Sistema tubular denso
Sistema canalicular
abierto
Mitocondria
Receptores
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High ShearGLICOPROTEINAS DE MEMBRANA
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Factor Von Willebrand
CirculaciónInmobilización
Alto Shear
> AFINIDAD< AFINIDAD
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Translocación
Activación
Adhesión Adhesión Adhesión Adhesión
ADHESION PLAQUETARIA AL FvW ADHESION PLAQUETARIA AL FvW ADHESION PLAQUETARIA AL FvW ADHESION PLAQUETARIA AL FvW
GPIb GPIIbIIIa
Rodamiento Rodamiento Rodamiento Rodamiento
FvWFvW
Adhesión Adhesión Adhesión Adhesión
irreversibleirreversibleirreversibleirreversible
Subendotelio
Rodamiento Rodamiento Rodamiento Rodamiento
inicialinicialinicialinicial
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Gránulos densos
ATP
ADP
����200-300 nm����
ADP
Cationes divalentes
Serotonina
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PLA2
Inside-out
Outside-in
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GP IIbIIIa
Es la glicoproteína más abundante en la membrana de la plaqueta.
En su estado inactivo esta integrina no puede unirse a sus ligandos
Une plaquetas activadas a través de puentes de fibrinógeno.
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Agregación PlaquetariaAgregación Plaquetaria
Fibrinógeno
GPIIbIIIa activada
FvW
GPIIbIIIa activada
Plaqueta
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GPGPGPGPGPGPGPGP
GP GP IIbIIb IIIaIIIa GP GP IbIb o IXo IX
TromboasteniaTromboasteniade de GlanzmannGlanzmann
Bernard Bernard SoulierSoulier
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Señales IntracelularesSeñales Intracelulares
GQ
STD
↑↑↑↑Calcio
PLC
PIP2DAG
IP3
↑↑↑↑Calcio
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Señales IntracelularesSeñales Intracelulares
cox
↑↑↑↑CalcioPLA2
AAPG2 y PH2
TTXXAA22
cox
txs
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Señales IntracelularesSeñales Intracelulares
MiosinaMiosina
PIP2 DAG
IP3
PKC
MiosinaMiosina
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Gránulos alfa
SolublesMoléculas de
adhesión
Fibrinógeno Factor vW GP IIbIIIa
Factor V Trombospondina GP Ib-V-IX
����200-500 nm����
Factor V Trombospondina GP Ib-V-IX
IgG, A y M ββββ-Tromboglobulina Factor plaquetario-4
GP VI
AlbúminaFibronectina
EGFPDGFTGF-βVEGFSDF-1
PECAM-1P-selectina
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Lisosomas
Hidrolasas ácidas
ß-glucuronidasa ß-galactosidasaß-glucuronidasa ß-galactosidasa
Catepsinas
Endoglucosidasa
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Retracción del coágulo
La retracción del coágulo resulta en una masa estabilizada de plaquetas y de fibrina que cierra firmemente el vaso injuriado para
prevenir futuras pérdidas de sangre.
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Fisiológicos Patológicos
Cancer
Aterosclerosis
Plaquetas
Hemostasia
Remodelación tisular
Desórdenes trombóticos
CancerPlaquetas
Inflamación
Respuesta Inmune
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Abluminalgrowth
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InflamaciónInflamación
AterosclerosisAterosclerosis
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Factores deFactores deFactores deFactores de
riesgoriesgoriesgoriesgo
tradicionalestradicionalestradicionalestradicionales
Cigarrillo, Hiperlipidemia, Lipidos Oxidados, Shear Stress, IROs,
Sindrome metabólico
NNNNuevos uevos uevos uevos Factores de Factores de Factores de Factores de
riesgo riesgo riesgo riesgo
Chlamydia HerpesHelicobacter PCR,
Homocisteína
Disfunción Endotelial
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ACIP
PGI2
PKGPKGIP3
IP3
GMPc
ON
↓↓↓↓ Ca2+
Intracelular
Kinasasdependientes
de cAMP
PIP3
↓↓↓↓ Ca2+
intracelular
Kinasasdependientes
de cGMP
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Endotelio
Plaquetas
CMLs
..... ......... .... ..... ....
..... ....
Leucocitos
CaCaCaCa2+2+2+2+NOSL-Arg
ONONONON GMPcGMPcGMPcGMPc
EritrocitosAdhesión
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ESTÍMULOS
P-SELECTINA
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P-Selectina/PSGL-1
Lectina EGF 2-9 Dom CR
Plaqueta
CélulaEndotelial
CélulaEndotelial
Plaqueta
Activadas
PMN
Monocito
PSGL-1SLx
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PSGL1 GPIbP-selP-sel
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PF4 IL-6
GPIb
IL-1β
IL-1β
IL-1β
PSGL1
P-sel
PF4PF4
PF4
NFκB
VCAM-1E-sel αvβ3 P-selICAM-1
IL-8
MCP1MCP1
IL-8
IL-6
IL-6FvWGM-CSF
GM-CSF
MMPs
MMPs
EROS
P-sel
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PSGL1 PSGL1
P-sel
PSGL1
P-selP-sel
PSGL1
PSGL1
PSGL1P-selPSGL1 PSGL1
PSGL1
PSGL1
P-sel
PSGL1
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P-selPSGL1
NFκB
L-sel
β1
β2
CD15
EROS EROSNFκB
IL-8
MCP1
FT
IL-8 IL-1β
MCP1TNF-α
TNF-αFT
SOBREVIDA
EROSEROS
EROS
EROS
IL-1βLKs LKs LKs LKs
catepsinas
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P-selPSGL1
NFκB
β1
β2
CD15
EROS EROS
NFκB
NFκBEROSEROS
IL-8
MCP1
FT
IL-8 IL-1β
MCP1TNF-α
TNF-αFT
SOBREVIDA
EROS
EROS
IL-1βLKs LKs LKs LKs
catepsinas
PROLIFERACIÓNFactores
de crecimiento
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Hansson y Libby, Nature Rev, 2006
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Micropartículas
Función pro-
agregante/coagulante
Las MP expresan integrinas y tienen proteínas
protrombóticas en su superficie como la P-selectina
y factor tisular.
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Factor VII A
Trombina
Fibrina
FTPSGL1
PSGL1P-sel P-selP-sel
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PSGL1P-sel P-selP-sel
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αvβ3
Fibrinogen
mucin
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NK
NK CELL
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PSGL1 GPIb
P-sel P-sel
SDF-1
VEGF
ANGIOGENESIS
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PLAQUETAS Y RESPUESTA
INMUNE
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REDES EXTRACELULARES DE ADN LIBERADAS POR NEUTROFILOS (NETs)
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MUCHAS GRACIAS!
TROMBOSIS I DEL IIHEMA