BONE MARROW FAILURE IN MALE RATS FOLLOWING TRAUMA/HEMORRHAGIC SHOCK (T/HS) IS MEDIATED BY MESENTERIC LYMPH AND MODULATED BY CASTRATION

Abstract

Bone marrow (BM) suppression occurs following trauma/hemorrhagic shock (T/HS) in experimental animals as well as following severe injury in humans. Although the pathophysiology of BM suppression remains poorly understood, mesenteric lymph is thought to play an important role in T/HS-induced BM suppression; however, the direct effect of mesenteric lymph on BM in vitro has never been studied. In addition, recent studies in rats have also shown that female and castrated male rats are protected against T/HS-induced BM failure. We therefore hypothesized that mesenteric lymph is a source of factor(s) causing direct BM suppression and that the effects of mesenteric lymph are gender dependent. To test this hypothesis, we subjected noncastrated (NC) and castrated (C) male and proestrus female rats to T/HS or trauma sham shock (T/SS). Mesenteric lymph collected 3 h postshock was plated (4% v/v) with BM cells collected from unmanipulated male or female rats for granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E) colony growth. The T/HS lymph collected from NC-male rats but not from female rats caused a 50% inhibition of CFU-GM and BFU-E colony growth compared with cells cultured without lymph (P < 0.05 versus all other groups (ANOVA + Tukey). T/HS lymph collected from C-male rats also caused no significant inhibition of CFU-GM and BFU-E colony growth compared with cells cultured without lymph. Female and male BM progenitor cells had a similar response to mesenteric lymph from all groups tested. These results show that mesenteric lymph from NC-male rats suppresses CFU-GM and BFU-E progenitor growth in vitro, whereas the lymph from C-male and female rats did not. The effects of mesenteric lymph were the same regardless of whether the target BM was from male or female rats. The results therefore indicate that BM failure in male rats is directly mediated by factors present within the mesenteric lymph that appear to be modulated by castration, and protection against BM failure in female rats occurs at a systemic rather than a local level. Further studies are needed to elucidate potential therapeutic effects of lymph manipulation in hematopoiesis after injury.