Chronic ethanol ingestion by mice increases expression of CD80 and CD86 by activated macrophages.
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-gamma). 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.
Zhu
Xiaoyan
X
Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Coleman
Ruth A
RA
Alber
Carol
C
Ballas
Zuhair K
ZK
Waldschmidt
Thomas J
TJ
Ray
Nancy B
NB
Krieg
Arthur M
AM
Cook
Robert T
RT
D000428:Alcohol Drinking / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D018122:B7-1 Antigen / Q000096:biosynthesis*; D051940:B7-2 Antigen; D000431:Ethanol / Q000008:administration & dosage*; D008262:Macrophage Activation / Q000187:drug effects* / Q000502:physiology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012646:Self Administration; D013154:Spleen / Q000166:cytology / Q000378:metabolism
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D000431:Ethanol