Abstract

The “Spartathlon” ultradistance foot race (246 Km continuous, prolonged, brisk exercise for up to 36 hours) provides a unique model of prolonged duration exercise that reveals dramatic systemic inflammatory changes. Endothelial progenitor cells (EPCs) have been shown to participate in vascular repair and angiogenesis, while circulating bone marrow originated fibrocytes represent multipotent cells mediating tissue repair and remodeling after injury. In this study we investigated the effect of this type of exercise on the number of circulating EPCs and fibrocytes along with molecules of endothelium dysfunction and chemotactic proteins in 10 “Spartathlon” athletes before, at the end and at 48 h post race. The EPCs were obtained by culturing peripheral blood mononuclear cells (PBMC) under endothelial cell conditions (EndoCult) and were measured as colony-forming units (CFUs). Circulating fibrocytes were cultured from PBMCs in IMDM medium supplemented with IL-3 and M-CSF and identified as CD45+CD14+CD34lowCollagen-I+ fibroblastic cells. We also determined the plasma levels of E-, L- and P-selectins, sICAM-1, sVCAM-1, thrombomodulin, lipocalin-2, IL-8 and MCP-1 with appropriate methodology. Circulating EPCs increased by nearly ten-fold in peripheral blood at the end of the “Spartathlon” race (from 48±15 cells/ml to 464±36 cells/ml) and they remained increased (420±28 cells/ml) even at 48h post race. The percentage of the CD45+CD14+CD34lowCollagen-I+ fibrocytes cultured from PBMCs before, at the end, and 48 h post race did not reveal any significant difference (64.5±6.2% vs 70.8±8.5% vs 68±4.8% respectively). Plasma levels of lipocalin-2, IL-8, MCP-1, E-selectin, sICAM, sVCAM and thrombomodulin were increased significantly at the end of the race and returned at the pre race levels 48 h post race, while L- and P-selectins remained unaffected before and at the end of the race, presenting a similar decline at 48 h post race. Our study demonstrates that acute inflammatory tissue damage induced by exhausting exercise increases EPCs but not fibrocytes. Given the ability of EPCs to promote angiogenesis and vascular regeneration and the association of fibrocytes with tissue fibrosis after persistent inflammation, we conclude that this kind of repair cell mobilization may serve as a physiologic repair mechanism in acute inflammatory tissue injury.

Author notes

Disclosure: No relevant conflicts of interest to declare.