title: p38 MAPK is activated but not necessary in porcine von Willebrand factor-dependent platelet activation.
abstract: We have investigated the role of p38 mitogen-activated protein kinase (MAPK) in von Willebrand factor (VWF)-dependent platelet activation. The interaction of platelets with subendothelial VWF, especially under high shear stress, is considered to be the first activation step which primes platelets for subsequent haemostatic events. As a model of VWF-dependent platelet activation, porcine VWF was employed. Porcine VWF induced p38 MAPK activation by 1 min post-addition; assessed by phosphorylation of a recombinant p38 MAPK fusion protein substrate termed glutathione S-transferase-MAPK activated protein kinase-2. To determine if p38 MAPK was necessary for porcine VWF-induced platelet activation, we functionally inhibited p38 MAPK activity with SB203580 before exposure of the platelets to porcine VWF. Inhibition of p38 MAPK had no effect on VWF-induced platelet alpha or lysozomal granule release, expression of activated GPIIb IIIa, modulation of membrane glycoprotein CD41, expression of phosphatidylserine as assessed by annexin V binding, microparticle formation, or platelet agglutination. It was concluded that SB203580-inhibitable p38 MAPK activity induced by porcine VWF is not necessary for platelet activation.
authors.affiliation: Department of Immunohaematology, St Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Song
authors.forename: J
authors.initials: J
authors.lastname: Freedman
authors.forename: M
authors.initials: M
authors.lastname: Mody
authors.forename: A H
authors.initials: AH
authors.lastname: Lazarus
mesh_terms: D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D015539:Platelet Activation / Q000502:physiology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases; D014841:von Willebrand Factor / Q000502:physiology*
chemical_list: D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014841:von Willebrand Factor; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D013917:Thrombin