Platelet aggregates-induced human CD34+ progenitor cell proliferation and differentiation to macrophages and foam cells is mediated by stromal cell derived factor 1 in vitro.
The chemokine stromal cell derived factor 1 (SDF-1) regulates chemotactic recruitment (homing) and differentiation of CD34 (+) stem cells. Platelets express substantial amounts of SDF-1 upon activation. The aim of the present study was to evaluate the role of SDF-1 in platelet-induced proliferation and differentiation of human CD34 (+) cells to macrophages and foam cells, as well as in regulation of matrix metalloproteinase (MMP)-9 secretion. Co-culture experiments of platelet thrombi (2 x 10(8)/mL) with human CD34 (+) progenitor cells resulted in platelet phagocytosis by the latter, causing their differentiation into CD68-positive macrophages and subsequent Sudan red III-positive foam cells. Platelet aggregates-induced foam cell generation and MMP-9 secretion were attenuated by a neutralizing monoclonal antibody against platelet-derived SDF-1, as evaluated by immunofluorescence microscopy and gelatin zymography. Co-culture experiments of human arterial endothelial cells and human CD34 (+) progenitor cells resulted in a fourfold increased proliferation of CD34 (+) cells in the presence of platelets being mainly regulated by platelet-derived SDF-1 in vitro. These findings imply that in the presence of platelet thrombi, CD34 (+) progenitor cells phagocytize platelets in an SDF-1 dependent manner, causing their differentiation into macrophages and then foam cells, a mechanism most likely contributing to atherogenesis and atheroprogression.
Stellos
Konstantinos
K
Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard Karls-Universität Tübingen, Tübingen, Germany. konstantinos.stellos@med.uni-tuebingen.de
Seizer
Peter
P
Bigalke
Boris
B
Daub
Karin
K
Geisler
Tobias
T
Gawaz
Meinrad
M
D018952:Antigens, CD34; D001792:Blood Platelets / Q000166:cytology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000502:physiology*; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology; D005487:Foam Cells / Q000166:cytology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008264:Macrophages / Q000166:cytology*; D010587:Phagocytosis; D010974:Platelet Aggregation / Q000502:physiology*; D013927:Thrombosis / Q000276:immunology / Q000473:pathology
D018952:Antigens, CD34; D054377:Chemokine CXCL12