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

Abstract

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.

Demonstration of mRNA for five species of cytochrome P450 in human bone marrow, bone marrow‐derived macrophages and human haemopoietic cell lines

“…The adherent cells were cultured in fresh medium for 3–4 days. Previous studies have shown that more than 85% of the adherent cells are macrophages, as judged by positivity for α‐naphthyl acetate esterase activity ( Wickramasinghe & Hasan, 1993).…”

Nitric Oxide Production and Nitric Oxide Synthase Type 2 Expression by Human Mononuclear Phagocytes: A Review

“…In studies of the effects of ethanol on bone marrow cell growth, Wickramasinghe and Hasan found that human bone marrow macrophages produced low levels of nitrite; this production could be inhibited by NMMA (35). Whereas ethanol inhibited thymidine and leucine incorporation into bone marrow cells, it did not influence nitrite production, and NMMA did not influence the ethanol effect.…”

Neutropenia during HIV Infection: Adverse Consequences and Remedies

“…Alcohol induces a profound inhibition of myeloid progenitor cell proliferative activity in hosts carrying the HIV-1 tat gene product [206]. Alcohol can also exert direct damages to the marrow hematopoietic niche microenvironment [190, 195, 198, 207–210]. Alcohol abuse is known to cause osteoporosis and osteonecrosis [207].…”