Lec 2-Platelet Ultrastructure-Part 2.pdf

MT 64 | A.Y. 2024-2025 PLATELET PLASMA MEMBRANE RECEPTORS (PLATELET ADHESION AND INITIATION OF AGGREGATION) Electrophoresis Current Nomenclature Ligand Comments Nomenclature GP Ia/IIa Integr...

MT 64 | A.Y. 2024-2025 PLATELET PLASMA MEMBRANE RECEPTORS (PLATELET ADHESION AND INITIATION OF AGGREGATION) Electrophoresis Current Nomenclature Ligand Comments Nomenclature GP Ia/IIa Integrin: α2β1 Collagen Avidity is upregulated via “inside- out” activation that depends on collagen binding to GP VI. Integrin: αvβ1 Vitronectin Integrin: α5β1 Laminin Integrin: α6β1 Fibronectin GP VI CAM of the Collagen Key collagen receptor, triggers immunoglobulin gene activation and release of agonists family that increase the avidity of integrins αIIbβ3 GP IV Collagen, Key collagen receptor (unclassified) thrombospondin GP Ib/IX/V CAM of the leucine-rich VWF and thrombin bind GP Ib/IX/V is a 2:2:2:1 complex of repeat family GP Ibα; thrombin GP Ibα and Ibβ, GP IX, and GP V. cleaves a site on GP V GP Ibα is the VWF-specific site. GP IIb/IIIa Integrin: αIIbβ3 Fibrinogen GP IIb and IIIa are distributed on the surface membrane, SCCS and α- granule membranes. Heterodimer forms on activation. SEVEN-TRANSMEMBRANE REPEAT RECEPTORS Receptor Ligand G-Protein Effect PAR1 Thrombin G1 Deceleration of adenylate cyclase and reduction in Gq cAMP G12 Activation of phospholipase C and increase of IP3-DAG Activation of protein kinase C and actin microfilaments PAR4 Thrombin Gq Activation of phospholipase C and increase of IP3-DAG G12 Activation of protein kinase C and actin microfilaments P2Y1 ADP Gq Activation of phospholipase C and increase of IP3-DAG G12 Activation of protein kinase C and actin microfilaments P2Y12 ADP G1 Deceleration of adenylate cyclase and reduction in cAMP TPα and TPβ TXA2 Gq Activation of phospholipase C and increase of IP3-DAG G12 Deceleration of adenylate cyclase and reduction in cAMP α2-adrenergic Epinephrine G1 Deceleration of adenylate cyclase and reduction in cAMP IP PGI2 (prostacyclin) GS Acceleration of adenylate cyclase and increase in cAMP 5HT2A Serotonin Gq Activation of phospholipase C and increase of IP3- DAG PREPARED BY: KAREN B. ROSETE, RMT 1  MT 64 | A.Y. 2024-2025 ADDITIONAL MEMBRANE RECEPTORS ❖ Intercellular adhesion molecules or ICAMs (CD50, CD54, CD102)  inflammation and immune reaction ❖ Platelet-endothelial cell adhesion molecule or PECAM (CD31)  mediates platelet-to-white blood cell and platelet-to-endothelial cell adhesion ❖ FcγIIA (CD32)  low-affinity receptor for the immunoglobulin Fc portion  associated with heparin-induced thrombocytopenia ❖ P-selectin (CD62)  Integrin; facilitates platelet binding to endothelial cells, leukocytes, and one another  Resting platelet: located on the alpha-granule membrane | Activated platelet: migrates via the SCCS to the surface  P-selectin quantification (flow cytometry): measurement of in vivo platelet activation MAIN REFERENCES: ❖ Keohane, E.M., Otto, C.N., Walenga, J.M. (2020). Rodak’s Hematology: Clinical Principles and Applications. (6th Ed.). Singapore: Elsevier ❖ Turgeon, M.L. (2012). Clinical Hematology: Theory and Procedures. (5th Ed.). Philadelphia: Lippincott Williams & Wilkins PREPARED BY: KAREN B. ROSETE, RMT 2