Badami Chirag D, Livingston David H, Sifri Ziad C, Caputo Francis J, Bonilla Larissa, Mohr Alicia M, Deitch Edwin A
Department of Surgery, New Jersey Medical School, Newark, NJ, USA.
J Trauma. 2007 Sep;63(3):596-600; discussion 600-2. doi: 10.1097/TA.0b013e318142d231.
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).
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.
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.
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.
创伤和失血性休克（T/HS）已被证明会导致人类和实验动物的骨髓（BM）抑制以及造血祖细胞（HPC）释放到外周血中。在T/HS后，许多终末器官中也发现了HPC，而BM中祖细胞的持续丢失可能在创伤后BM抑制中起作用。我们研究了以下假设：HPC会特异性迁移到组织创伤部位，并且失血性休克（HS）会加剧这一过程。
将因冲击式射钉枪冲击波导致单侧肺挫伤（LC）的Sprague-Dawley大鼠（250 - 400 g）分为HS组（平均动脉压40 - 45 mmHg，持续45分钟）或假休克（SS）组。复苏后3小时、3天和7天处死动物，将每只动物的左右肺分别处理，未受伤的左肺作为对照与挫伤的右肺进行比较。从每个肺和股骨中分离出BM单个核细胞并进行铺板（2×10），一式两份用于粒细胞 - 巨噬细胞集落形成单位（CFU - GM）、红系集落形成单位（CFU - E）和红系爆式集落形成单位（BFU - E）的集落生长。
在3小时时，与未受伤的肺相比，LC导致受伤肺中能够生长的祖细胞集落显著增加（CFU - GM：每10个BM单个核细胞中11±1 vs. 5±2，CFU - E：12±7 vs. 5±3，BFU - E：7±1 vs. 3±1个集落；所有p < 0.05）。HS导致未受伤和挫伤肺中所有三种细胞类型的集落数量均显著增加（所有p < 0.05）。在HS后第3天，BM祖细胞生长仍受到抑制，而从肺中可回收的细胞数量恢复到基线水平。到第7天，BM中造血祖细胞生长以及从肺中能够生长的这些细胞数量恢复到未处理大鼠中观察到的水平。
单侧LC导致大量HPC从BM快速动员到损伤部位。在这种情况下BM功能得以维持。HS的加入增加了HPC从BM的动员和在损伤部位的滞留，同时降低了BM中HPC的生长。我们推测，损伤组织中祖细胞的积累以及正常BM归巢的改变，如肺中祖细胞减少而BM功能未恢复，在创伤后BM抑制中起作用。休克介导的从BM动员的机制以及这些细胞在损伤部位的确切作用和命运需要进一步研究。
