Mobilization of Endothelial Progenitor Cells From Bone Marrow is Impaired in a Piglet Model of Acute Respiratory Distress Syndrome*

Abstract

To characterize the endothelial progenitor cell mobilization in the models of moderate and severe lung injury, we hypothesized that there were differences in endothelial progenitor cell levels and mobilizing cytokines between moderate and severe lung injury. Prospective, randomized, and controlled experimental study. University research laboratory center. Fifteen healthy piglets. Piglets were randomly allocated to control, moderate lung injury (acute lung injury), and severe lung injury (acute respiratory distress syndrome) groups. Lung injury was established by intravenous infusion of oleic acid. Animals were mechanically ventilated for 24-48 hours, and then animals were weaned from ventilation and cared for until day 7. Endothelial progenitor cells were quantified by flow cytometry. After 24 hours, the number of endothelial progenitor cells in peripheral blood increased in the acute lung injury group but was not altered in the acute respiratory distress syndrome group compared to the control group. The number of CD34KDR, KDRCD133, and CD34KDRCD133 cells was higher in the acute lung injury group than in the acute respiratory distress syndrome group. In bone marrow, the number of CD34KDR and KDRCD133 cells was greater in acute respiratory distress syndrome animals but not altered in acute lung injury animals at 24 hours. Furthermore, plasma stromal cell-derived factor-1 and vascular endothelial growth factor concentrations were higher in acute lung injury than in acute respiratory distress syndrome at 24 hours. Matrix metalloproteinase-9 and soluble kit ligand levels in bone marrow were reduced in acute respiratory distress syndrome compared with acute lung injury. Lung CD34, KDR, and lung stromal cell-derived factor-1 messenger RNA expression were higher in the acute lung injury group than in the acute respiratory distress syndrome group. Furthermore, the expression of CD34, KDR, and CD133 messenger RNA in lung tissue was correlated with stromal cell-derived factor-1 in the lung. There was a rapid release of endothelial progenitor cells from bone marrow into circulation in moderate acute lung injury, and endothelial progenitor cell mobilization was impaired in acute respiratory distress syndrome.