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 dysregul ation. Since the BM is the major organ of immune cells in the adult, its fa ilure 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 report ed in hypoxia and hemorrhagic shock, hypoxia alone could be a representativ e model to study BM responses during hemorrhagic shock. In this study, we u se an animal model to dissect the hematopoietic effects of hypoxia. We subj ected rats to hypoxia, and at days 1 and 5 post-hypoxia we determined the n umbers of granulocytic-monocytic progenitors (CFU-GM) in the BM. We found s ignificant increase (P < 0.05) in CFU-GM at day 1 and a downward trend by d ay 5. Enhanced BM cellularity could not explain the increase in CFU-GM by d ay 1. BM stromal cells mediated most of the stimulatory effects by hypoxia. CFU-GM was inversely proportional to bioactive TGF-beta and directly propo rtional 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 p artially mediated through the BM stroma. In the absence of a second insult, CFU-GM reverts to baseline. The data also suggest that hypoxia mediates co mplex 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. Am. J. Hema tol. 64:20-25, 2000. (C) 2000 Wiley-Liss, Inc.