Possible role of macrophages in the pathogenesis of ethanol‐induced bone marrow damage

Adherent-cell-depleted human marrow cells (MC) were cultured on their own or co-cultured with monolayers of blood-monocyte-derived macrophages or marrow-derived adherent cells with and without 2 mg ethanol/ml for 24 h. The incorporation of 3H-thymidine and 3H-leucine by MC cultured on their own was not significantly influenced by ethanol. By contrast, the incorporation of both radiolabelled compounds was significantly lower in MC from the co-cultures containing ethanol than from those not containing ethanol. This effect was mediated by a diffusible factor produced by macrophages in the ethanol-containing cultures and was independent of intercellular contact. Supernatants from ethanol-containing cultures of marrow-derived adherent cells displayed cytotoxic activity against A9 cells due to the presence of unstable acetaldehyde-albumin complexes. Ethanol inhibited rather than stimulated nitrite production in the MC/marrow-derived adherent cell co-culture system, suggesting that macrophage-derived nitric oxide did not play a role in causing the observed ethanol-related effects. The data indicate that, in the presence of ethanol, macrophages cause inhibition of the incorporation of 3H-thymidine and 3H-leucine into overlying MC, at least partly by oxidizing ethanol to acetaldehyde and releasing some of the potentially cytotoxic acetaldehyde thus formed extracellularly. Bone marrow macrophages may therefore play an important role in the pathogenesis of alcohol-related marrow damage in vivo.