title: High shear flow induces migration of adherent human platelets.
abstract: Shear forces are generated in all parts of the vascular system and contribute directly and indirectly to vascular disease progression. Endothelial cells are able to adapt to flow conditions, and are known to polarize and migrate in response to shear forces. Platelets exposed to shear stress are activated and release bioactive molecules from their alpha granules. So far, platelets have been considered to be static cells that do not leave the site of tight adhesion. However, we have recently been able to demonstrate the capacity of platelets to migrate in response to stromal derived factor-1 (SDF-1). In this project, we have demonstrated that platelets accumulate in areas with a high concentration of SDF-1 under flow conditions and respond to high shear stress by cellular polarization, cytoskeletal reorganisation, and flow-directed migration. In this context, we have shown increased Wiskott-Aldrich Syndrome protein (WASP) phosphorylation and intracellular redistribution of focal adhesion kinase (FAK) under high-shear stress conditions. The effect of flow-induced platelet migration has not previously been recognized and offers a new role for platelets as mobile cells. Their migratory potential may enable platelets to cover intimal lesions and contribute to vascular repair.
authors.affiliation: Universitätsklinikum Tübingen, Medizinische Klinik III für Herz-und Kreislauferkrankungen, Tübingen, Germany.
authors.forename: Bjoern F
authors.initials: BF
authors.lastname: Kraemer
authors.forename: Christine
authors.initials: C
authors.lastname: Schmidt
authors.forename: Benjamin
authors.initials: B
authors.lastname: Urban
authors.forename: Boris
authors.initials: B
authors.lastname: Bigalke
authors.forename: Laura
authors.initials: L
authors.lastname: Schwanitz
authors.forename: Miriam
authors.initials: M
authors.lastname: Koch
authors.forename: Peter
authors.initials: P
authors.lastname: Seizer
authors.forename: Martin
authors.initials: M
authors.lastname: Schaller
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
authors.forename: Stephan
authors.initials: S
authors.lastname: Lindemann
mesh_terms: D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D016764:Cell Polarity; D054377:Chemokine CXCL12 / Q000378:metabolism / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000378:metabolism; D005434:Flow Cytometry; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000096:biosynthesis; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D018613:Microscopy, Confocal; D010766:Phosphorylation / Q000187:drug effects; D013314:Stress, Mechanical; D051316:Wiskott-Aldrich Syndrome Protein / Q000378:metabolism
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D051316:Wiskott-Aldrich Syndrome Protein; D051416:Focal Adhesion Protein-Tyrosine Kinases