Hematopoietic Progenitor Cells Mobilize to the Site of Injury After Trauma and Hemorrhagic Shock in Rats

Abstract

BACKGROUND: Trauma and hemorrhagic shock (T/HS) has been demonstrated to result in bone marrow (BM) suppression and the release of hematopoietic progenitor cells (HPC) into the peripheral blood in both human beings and experimental animals. HPC have also been identified in numerous end organs after T/HS and the ongoing loss of progenitor cells from the BM may play a role in posttraumatic BM suppression. We investigated the hypothesis that HPC will specifically migrate to sites of tissue trauma and that this process is exacerbated by hemorrhagic shock (HS). METHODS: Sprague-Dawley rats (250-400 g) sustaining a unilateral lung contusion (LC) secondary to a blast wave of a percussive nail gun, were subjected to either HS (MAP 40-45 mm Hg for 45 minutes) or sham shock (SS). Animals were killed at 3 hours, 3 days, and 7 days after resuscitation and the right and left lungs from each animal were processed separately and the uninjured left lung served as a control for comparison with the contused right lung. BM mononuclear cells from each individual lung and the femurs were isolated and plated (2 x 10) in duplicate for granulocyte-macrophage colony-forming units (CFU-GM), erythroid colony-forming units (CFU-E), and erythroid burst-forming units (BFU-E) colony growth. RESULTS: At 3 hours, LC resulted in a significant increase in progenitor colonies able to be grown from the injured lung compared with from the uninjured lung (CFU-GM: 11 +/- 1 vs. 5 +/- 2, CFU-E: 12 +/- 7 vs. 5 +/- 3, BFU-E: 7 +/- 1 vs. 3 +/- 1 colonies per 10 BM mononuclear cells; all p < 0.05). HS resulted in a significant increase of the number of colonies of all three cell types in both the uninjured and the contused lung (all p < 0.05). At day 3 after HS, BM progenitor growth remained suppressed whereas the number of cells recoverable from the lung returned toward baseline. By day 7, hematopoietic progenitor cell growth in the BM and the number of those cells able to be grown from the lung returned to levels observed in unmanipulated rats. CONCLUSION: Unilateral LC results in the rapid mobilization of a significant number of HPC from the BM to the site of injury. BM function is maintained under this condition. The addition of HS increases HPC mobilization from the BM and sequestration at the site of injury as well as decreasing BM HPC growth. We postulate that the accumulation of progenitor cells in the injured tissue combined with an alteration of normal BM homing, as exemplified by the decrease in progenitor cells from the lung without restoration of BM function, plays a role in posttraumatic BM suppression. The mechanism of shock-mediated mobilization from the BM and the exact role and fate of these cells at the site of injury requires further investigation.