Trauma inhibits erythroid burst-forming unit and granulocyte-monocyte colony-forming unit growth through the production of TGF-beta 1 by bone marrow stroma

Objective To examine the effect of trauma plasma on clonogenic progenitor cultures. Summary Background Data Severely Injured trauma patients often experience altered hematopoietic fun ctions, manifested by an increased susceptibility to infection and the deve lopment of a persistent anemia. Experimental and clinical data suggest that trauma results in the release of cytokines into the plasma that have hemat opoietic regulatory function, but few studies have examined human bone marr ow. Methods Plasma was obtained from 42 severely injured patients admitted to the surgi cal intensive care unit from days 1 to 15 after injury. Bone marrow and nor mal plasma were obtained from volunteers. Bone marrow mononuclear cells wer e isolated and plated for granulocyte-monocyte colony-forming unit (CFU-GM) and erythroid burst-forming unit (BFU-E) growth. Parallel cultures were in cubated with 2% (v/v) trauma or normal plasma. Additional cultures were pla ted with neutralizing concentrations of antibodies to transforming growth f actor (TGF)-beta1 and MIP-1 alpha. Circulating plasma TGF-beta1 was deter-m ined by bioassay. mRNA from bone marrow stromal cultures was extracted and probed for TGF-beta1 and macrophage Inflammatory protein (MIP)-1 alpha. Results Trauma plasma suppressed CFU-GM and BFU-E colony growth by 40% to 60% at al l time periods after injury compared with cultures incubated with normal pl asma. Using a noncontact culture system, the authors showed that this inhib ition of BFU-E and CFU-GM colony growth was mediated by bone marrow stroma. The inhibition appeared to be due to soluble plasma-induced bone marrow st romal products that did not require direct cell-cell contact. The addition of anti-TGF-beta1 antibodies reversed the suppressive effect of trauma plas ma on CFU-GM and BFU-E colony growth during the early but not late time poi nts after injury. Trauma but not normal plasma Induced TGF-PI mRNA In bone marrow stroma. Conclusions Trauma plasma inhibits bone marrow BFU-E and CFU-GM colony growth for up to 2 weeks after Injury. This inhibition is mediated through the interaction of trauma plasma with bone marrow stroma. TGF-beta1 production by bone marr ow stroma appears to plays an important role in the early but not late bone marrow suppression after injury.