Effects of hypoxia on granulocytic-monocytic progenitors in rats. Role of bone marrow stroma.
Hemorrhagic shock leads to hypoxia and is associated with bone marrow (BM) failure. Hemorrhagic shock is also a predisposing factor in immune dysregulation. Since the BM is the major organ of immune cells in the adult, its failure following hemorrhagic shock may explain the increased susceptibility to infection. The in vitro evidence indicates that hypoxia mediates altered functions in BM stroma. Since similar hematopoietic alterations are reported in hypoxia and hemorrhagic shock, hypoxia alone could be a representative model to study BM responses during hemorrhagic shock. In this study, we use an animal model to dissect the hematopoietic effects of hypoxia. We subjected rats to hypoxia, and at days 1 and 5 post-hypoxia we determined the numbers of granulocytic-monocytic progenitors (CFU-GM) in the BM. We found significant increase (P < 0.05) in CFU-GM at day 1 and a downward trend by day 5. Enhanced BM cellularity could not explain the increase in CFU-GM by day 1. BM stromal cells mediated most of the stimulatory effects by hypoxia. CFU-GM was inversely proportional to bioactive TGF-beta and directly proportional to IL-1. Compared to normoxic rats, IL-6 production was suppressed in BM cells from hypoxic rats. The results show that hypoxia alone initiate a stimulatory response in CFU-GM progenitors. These effects are at least partially mediated through the BM stroma. In the absence of a second insult, CFU-GM reverts to baseline. The data also suggest that hypoxia mediates complex responses that include cytokine production. These results add to the current understanding of hematopoietic responses by hypoxia and adds to the mechanisms of immune dysfunctions following hemorrhagic shock.
Taneja
R
R
Department of Surgery, UMDNJ-New Jersey Medical School, Newark, USA.
Rameshwar
P
P
Upperman
J
J
Wang
M T
MT
Livingston
D H
DH
D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D006098:Granulocytes / Q000166:cytology / Q000502:physiology; D000860:Hypoxia; D019891:Leukopoiesis / Q000502:physiology*; D009000:Monocytes / Q000166:cytology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology*