Chronic ethanol ingestion by mice increases expression of CD80 and CD86 by activated macrophages☆

Abstract 

Results from previous studies from our laboratory have shown that T cells obtained from the spleens of C57BL/6 mice that consumed ethanol chronically have increased expression of activation markers and increased second signal–independent production of interferon-gamma (IFN-γ). We now report that in vitro–activated CD11b⁺ splenocytes obtained from C57BL/6 and BALB/c mice that consumed ethanol chronically express increased levels of the T cell co-stimulatory molecules CD80 and CD86. CD11b⁺ splenocytes encompass at least two populations: the CD11b⁺Gr.1⁻ population, which is primarily monocytes–macrophages, and a smaller CD11b⁺Gr.1⁺ population, which is in the myelocytic–monocytic cell series and contains precursors of both macrophages and neutrophils. Evaluation of cultures of purified CD11b⁺ cells, obtained from mice that consumed ethanol chronically, incubated overnight, showed increased up-regulation of CD80 and CD86 expression on Gr.1⁻ mouse splenic macrophages. Results of functional studies of purified CD11b⁺ cells have demonstrated that CD11b⁺ cells obtained from C57BL/6 mice that were exposed to ethanol chronically secrete higher levels, in comparison with the levels secreted by CD11b⁺ cells obtained from control animals, of nitric oxide and several proinflammatory cytokines after stimulation by the oligodeoxynucleotide (ODN) CpG 1826. These findings indicate that CD11b⁺ splenocytes are in some way sensitized to activating stimuli by chronic ethanol exposure in vivo. Such cells may contribute to systemic immunodysregulation, including T-cell activation, by providing abnormal second signals to T cells, or through excessive release of cytokines, such as interleukin (IL)-6 or IL-12.

Keywords:  Ethanol, Activated macrophages, CD80, CD86