title: Platelets secrete stromal cell-derived factor 1alpha and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo.
abstract: The accumulation of smooth muscle and endothelial cells is essential for remodeling and repair of injured blood vessel walls. Bone marrow-derived progenitor cells have been implicated in vascular repair and remodeling; however, the mechanisms underlying their recruitment to the site of injury remain elusive. Here, using real-time in vivo fluorescence microscopy, we show that platelets provide the critical signal that recruits CD34+ bone marrow cells and c-Kit+ Sca-1+ Lin- bone marrow-derived progenitor cells to sites of vascular injury. Correspondingly, specific inhibition of platelet adhesion virtually abrogated the accumulation of both CD34+ and c-Kit+ Sca-1+ Lin- bone marrow-derived progenitor cells at sites of endothelial disruption. Binding of bone marrow cells to platelets involves both P-selectin and GPIIb integrin on platelets. Unexpectedly, we found that activated platelets secrete the chemokine SDF-1alpha, thereby supporting further primary adhesion and migration of progenitor cells. These findings establish the platelet as a major player in the initiation of vascular remodeling, a process of fundamental importance for vascular repair and pathological remodeling after vascular injury.
authors.affiliation: Deutsches Herzzentrum and Medizinische Klinik, Technical University of Munich, D-80636 Munich, Germany. massberg@cbr.med.harvard.edu
authors.forename: Steffen
authors.initials: S
authors.lastname: Massberg
authors.forename: Ildiko
authors.initials: I
authors.lastname: Konrad
authors.forename: Katrin
authors.initials: K
authors.lastname: Schürzinger
authors.forename: Michael
authors.initials: M
authors.lastname: Lorenz
authors.forename: Simon
authors.initials: S
authors.lastname: Schneider
authors.forename: Dietlind
authors.initials: D
authors.lastname: Zohlnhoefer
authors.forename: Katharina
authors.initials: K
authors.lastname: Hoppe
authors.forename: Matthias
authors.initials: M
authors.lastname: Schiemann
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kennerknecht
authors.forename: Susanne
authors.initials: S
authors.lastname: Sauer
authors.forename: Christian
authors.initials: C
authors.lastname: Schulz
authors.forename: Sandra
authors.initials: S
authors.lastname: Kerstan
authors.forename: Martina
authors.initials: M
authors.lastname: Rudelius
authors.forename: Stefan
authors.initials: S
authors.lastname: Seidl
authors.forename: Falko
authors.initials: F
authors.lastname: Sorge
authors.forename: Harald
authors.initials: H
authors.lastname: Langer
authors.forename: Mario
authors.initials: M
authors.lastname: Peluso
authors.forename: Pankaj
authors.initials: P
authors.lastname: Goyal
authors.forename: Dietmar
authors.initials: D
authors.lastname: Vestweber
authors.forename: Nikla R
authors.initials: NR
authors.lastname: Emambokus
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
authors.forename: Jon
authors.initials: J
authors.lastname: Frampton
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001158:Arteries / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D001792:Blood Platelets / Q000378:metabolism* / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D002465:Cell Movement; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008856:Microscopy, Fluorescence; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D015539:Platelet Activation; D020127:Recovery of Function; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D013927:Thrombosis / Q000378:metabolism* / Q000473:pathology
chemical_list: D000943:Antigens, Differentiation; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse