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

• Published in: Alcohol (Fayetteville, N.Y.) N.Y.), 2004-02, Vol.32 (2), p.91-100
• Main Authors: Zhu, Xiaoyan, Coleman, Ruth A, Alber, Carol, Ballas, Zuhair K, Waldschmidt, Thomas J, Ray, Nancy B, Krieg, Arthur M, Cook, Robert T
• Format: Article
• Language: English
• Subjects: Activated macrophages; Alcohol Drinking - immunology; Alcoholism; Alcoholism and acute alcohol poisoning; Animals; Antigens, CD - biosynthesis; B7-1 Antigen - biosynthesis; B7-2 Antigen; Biological and medical sciences; CD80; CD86; Cytokines; Ethanol; Ethanol - administration & dosage; Immune system; Macrophage Activation - drug effects; Macrophage Activation - physiology; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Medical sciences; Membrane Glycoproteins - biosynthesis; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Self Administration; Spleen - cytology; Spleen - metabolism; Toxicology
• ISSN: 0741-8329; 1873-6823
• DOI: 10.1016/j.alcohol.2004.01.004

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.