Platelet ultrastructure Flashcards by pattie o.

Methods for studying platelet ultrastructure-

Scanning and transmission electron microscopy- flow cytometry- molecular sequencing

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Platelet plasma membrane function-

Selectively permeable- supports platelet activation and plasma coagulation

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Components anchored within the platelet membrane-

Glycoproteins and proteoglycans

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Neutral phospholipids in platelet membrane-

Phosphatidylcholine and sphingomyelin (outer plasma layer)

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Anionic phospholipids in platelet membrane-

Phosphatidylinositol- phosphatidylethanolamine- phosphatidylserine (inner cytoplasmic layer)

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Role of phosphatidylinositol in platelets-

Supports platelet activation by supplying arachidonic acid

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Phosphatidylserine function-

Flips to outer surface upon activation- provides charged surface for coagulation complexes

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Coagulation complexes assembled on phosphatidylserine surface-

TENASE complex and PROTHROMBINASE complex

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Glycocalyx function on platelet membrane-

Absorbs albumin- fibrinogen- and other plasma proteins through endocytosis

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Ligand definition-

A molecule that binds to another molecule- especially a small molecule binding to a larger molecule

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CAM definition-

Cell adhesion molecule

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GP Ia/IIa receptor type: Integrin α2β1-

Binds collagen

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GP Ia/IIa receptor type: Integrin αvβ1 receptor function-

Binds vitronectin

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GP Ia/IIa receptor type: Integrin α5β1 receptor function-

Binds laminin

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GP Ia/IIa receptor type: Integrin α6β1 receptor function-

Binds fibronectin

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GP VI receptor type-

CAM of the immunoglobulin gene family

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GP VI function-

Collagen receptor- triggers platelet activation

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GP VI activation result-

Release of TXA2 and ADP

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Effect of GP VI activation-

Increases avidity of integrins α2β1 and αIIbβ3

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GP Ib/IX/V receptor type-

CAM of the leucine-rich repeat family

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GP Ib/IX/V ligands-

VWF and thrombin bind GPIbα

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Effect of thrombin on GP Ib/IX/V-

Thrombin cleaves a site on GP V

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Bernard-Soulier syndrome cause-

Deficiency of GPIb/IX/V complex

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GP Ibα function-

VWF-specific binding site

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GP IIb/IIIa receptor type-

Integrin αIIbβ3

GP IIb/IIIa ligands-

Fibrinogen- VWF

GP IIb/IIIa function-

Key fibrinogen receptor

Glanzmann’s thrombasthenia cause-

Deficiency of GPIIb/IIIa

PAR 1- activates platelet; ligand:-

thrombin

PAR 4- activates platelet; ligand:-

thrombin

P2Y1- activates platelet; ligand:-

Adenosine diphosphate (ADP)

P2Y12- activates platelet; ligand:-

Adenosine diphosphate (ADP)

TPα and TPβ- activates platelet; ligand:-

Thromboxane A2 (TXA2)

α2-adrenergic- activates platelet; ligand:-

Epinephrine (Adrenaline)

IP- inhibits platelet activation; ligand:-

Prostaglandin I2 (PGI2) [Prostacyclin]

Platelet STR (Seven Transmembrane Repeat) Receptors-

PAR 1- PAR 4- P2Y1- P2Y12- TPα- TPβ- α2-adrenergic- IP

Platelet membrane receptor for Low-affinity receptor for immunoglobulin Fc- involved in heparin-induced thrombocytopenia (HIT)-

FcIIA (CD32)

Platelet membrane receptor for Integrin for platelet binding to endothelial cells- WBCs- and each other; found on α-granule membranes and surfaces of activated platelets; quantifiable by flow cytometry for in vivo platelet activation-

P-selectin (CD62)

Platelet cytoskeleton components controlling shape change- extension of pseudopods- and secretion-

Microtubules- actin microfilaments- and intermediate microfilaments

Microtubule formation-

Formed by tubulins

Function of microtubules in platelets-

Maintain discoid shape- move inward on activation- support pseudopods

Effect of cold temperature on platelets-

Microtubules disassemble- platelets become round

Effect of warming to 37°C on platelets-

Microtubules reassemble- platelets recover discoid shape

Function of microtubules during platelet activation-

Reassemble into parallel bundles to support rigidity of pseudopods

Microfilament location-

Between microtubules and the membrane

Microfilament formation-

Formed by actins

Function of actin in platelets-

Anchors plasma membrane glycoproteins and proteoglycans- present throughout cytoplasm

State of actin in resting platelets-

Globular and amorphous

Effect of increased cytoplasmic calcium on actin-

Becomes filamentous and contractile

Intermediate filaments in platelets-

Desmin and Vimentin- connect with actin and microtubules to maintain shape

Platelet granules flow through-

SCCS for α-granules and lysosomes- plasma membrane for dense granules

α-granules in each platelet-

50 to 80 granules

Staining of α-granules-

Medium-gray (osmium-dye transmission electron microscopy preparations)

Primary contents of α-granules-

Proteins that participate in secondary hemostasis (coagulation)

α-granule activation process-

Membranes fuse with SCCS- contents flow to nearby environment

Functions of α-granule contents in nearby environment-

Participate in platelet adhesion- aggregation- and support plasma coagulation

Protein present in α-granules (not in cytoplasm)-

β-thromboglobulin- PF-4 (platelet factor-4)- HMWK- PAI-1 (plasminogen activator inhibitor-1)- Plasminogen- Protein C inhibitor- EGF- PGDF- TGF-b

Protein from α-granules that inhibits heparin-

β-thromboglobulin- PF-4 (platelet factor-4)

Proteins from α-granules that support mitosis of vascular fibroblasts and smooth muscle cells-

EGF (endothelial growth factor)- PDGF (platelet-derived growth factor)- TGF-β (transforming growth factor-β)

Protein in α-granules and platelet cytoplasm-

Fibrinogen- Fibronectin- Albumin- Immunoglobulins- VWF- Thrombospondin- Factor V

Protein in α-granule membrane-

P-selectin

Proteins in α-granule membrane and plasma membrane-

GP IIb/IIIa- GP IV- GP Ib/IX/V

Number of dense granules per platelet-

2 to 7

Other name for dense granules-

Delta granules

Appearance of dense granules in electron microscopy-

Stain black (opaque) with osmium

Dense granule release upon platelet activation-

Contents released directly into plasma

Function of dense granules-

Vasoconstrictors and platelet agonists that intensify primary hemostasis

Definition of agonist-

A substance that initiates a response when combined with a receptor

Components of dense granules (MPCHASE)-

ADP- ATP- Phosphate- Serotonin (5-HT)- Histamine- Ca2+- Mg2+- Epinephrine

Supports neighboring platelet aggregation by binding to P2Y1 and P2Y12-

ADP

Function unknown- but ATP release is detectable upon platelet activation-

ATP

Vasoconstrictor that binds endothelial cells and platelet membranes-

Serotonin (5-HT)

Divalent cations support platelet activation and coagulation-

Ca2+ and Mg2+

Few in number- stain positive for arylsulfatase- β-glucuronidase- acid phosphatase- and catalase-

Lysosomes

Flow through SCCS- digest vessel wall matrix components during in vivo aggregation-

Lysosomes

Digest autophagic debris-

Lysosomes

SCCS serves as the route for-

endocytosis- secretion of α-granule contents- secretion of lysosome contents

Less developed in the SCCS and lacks some of the glycoprotein receptors present on the platelet surface-

Glycocalyx

Plasma membrane invades platelet interior- producing-

SCCS

Control center for platelet activation- closely aligned to the SCCS- condensed remnant of the rough endoplasmic reticulum- sequesters calcium and bears enzymes supporting platelet activation-

DTS (Dense Tubular System)

DTS Enzymes supporting platelet activation-

phospholipase A2- cyclooxygenase- thromboxane synthetase- phospholipase C

Enzymes that supports eicosanoid synthesis pathway producing thromboxane A2-

phospholipase A2- cyclooxygenase- thromboxane synthetase

Enzymes that supports production of inositol triphosphate (IP3) and diacylglycerol (DAG)-

phospholipase C

Most frequent anti-platelet drug- cyclooxygenase inhibitor-

Aspirin (acetylsalicylic acid)

Platelet ultrastructure Flashcards

(84 cards)