Platelets secrete stromal cell-derived factor 1alpha and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo.
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.
Massberg
Steffen
S
Deutsches Herzzentrum and Medizinische Klinik, Technical University of Munich, D-80636 Munich, Germany. massberg@cbr.med.harvard.edu
Konrad
Ildiko
I
Schürzinger
Katrin
K
Lorenz
Michael
M
Schneider
Simon
S
Zohlnhoefer
Dietlind
D
Hoppe
Katharina
K
Schiemann
Matthias
M
Kennerknecht
Elisabeth
E
Sauer
Susanne
S
Schulz
Christian
C
Kerstan
Sandra
S
Rudelius
Martina
M
Seidl
Stefan
S
Sorge
Falko
F
Langer
Harald
H
Peluso
Mario
M
Goyal
Pankaj
P
Vestweber
Dietmar
D
Emambokus
Nikla R
NR
Busch
Dirk H
DH
Frampton
Jon
J
Gawaz
Meinrad
M
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
D000943:Antigens, Differentiation; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse