Trauma inhibits erythroid burst-forming unit and granulocyte-monocyte colony-forming unit growth through the production of TGF-beta1 by bone marrow stroma.
OBJECTIVE
To examine the effect of trauma plasma on clonogenic progenitor cultures.


BACKGROUND
Severely injured trauma patients often experience altered hematopoietic functions, manifested by an increased susceptibility to infection and the development of a persistent anemia. Experimental and clinical data suggest that trauma results in the release of cytokines into the plasma that have hematopoietic regulatory function, but few studies have examined human bone marrow.


METHODS
Plasma was obtained from 42 severely injured patients admitted to the surgical intensive care unit from days 1 to 15 after injury. Bone marrow and normal plasma were obtained from volunteers. Bone marrow mononuclear cells were isolated and plated for granulocyte-monocyte colony-forming unit (CFU-GM) and erythroid burst-forming unit (BFU-E) growth. Parallel cultures were incubated with 2% (v/v) trauma or normal plasma. Additional cultures were plated with neutralizing concentrations of antibodies to transforming growth factor (TGF)-beta1 and MIP-1alpha. Circulating plasma TGF-beta1 was determined by bioassay. mRNA from bone marrow stromal cultures was extracted and probed for TGF-beta1 and macrophage inflammatory protein (MIP)-1alpha.


RESULTS
Trauma plasma suppressed CFU-GM and BFU-E colony growth by 40% to 60% at all time periods after injury compared with cultures incubated with normal plasma. Using a noncontact culture system, the authors showed that this inhibition 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 stromal products that did not require direct cell-cell contact. The addition of anti-TGF-beta1 antibodies reversed the suppressive effect of trauma plasma on CFU-GM and BFU-E colony growth during the early but not late time points after injury. Trauma but not normal plasma induced TGF-beta1 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 marrow stroma appears to plays an important role in the early but not late bone marrow suppression after injury.
Wu
J C
JC
Department of Surgery, Section of Trauma, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA.
Livingston
D H
DH
Hauser
C J
CJ
Deitch
E A
EA
Rameshwar
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000378:metabolism*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood*; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007377:Interleukin-3 / Q000097:blood*; D019402:Macrophage Inflammatory Proteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D014947:Wounds and Injuries / Q000097:blood* / Q000601:surgery
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D007377:Interleukin-3; D019402:Macrophage Inflammatory Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor