The Long‐term Impaired Macrophages Functions are Already Observed Early after High‐dose Ethanol Administration

Abstract

Herein, we described an experimental model of high‐dose ethanol (EtOH) administration, able to induce in vitro impairment in macrophage phagocytic capacity, already observed at 24 h after the last EtOH administration. This phenomenon was characterized by enlarged time required for adhesion and internalization events. Parallel studies documented an overall impaired production of interleukin (IL)‐6 and nitric oxide (NO) production by peritoneal macrophages in EtOH‐treated mice following interferon (IFN)‐γ and lipopolysaccharide (LPS) stimuli. Although the impaired IL‐6 response could not be restored by any of the experimental conditions tested, the lower NO response to INF‐γ and LPS was overturned by simultaneous IFN‐γ/LPS stimuli. It was interesting to notice that high‐dose EtOH administration drives peritoneal macrophages towards long‐term impairment in phagocytosis capacity with slower adhesion time, but with no impact on the time required for internalization. Moreover, 30 days after the last EtOH administration, lower IL‐6 response to INF‐γ and impaired NO production were still observed in response to IFN‐γ/LPS stimuli, with the IL‐6 response to IFN‐γ being restored by IFN‐γ/LPS stimuli. Histological studies showed that high‐dose EtOH administration led to long‐term in vivo impairment of antigen‐clearance following OVA‐driven delayed‐type‐hypersensitivity induction, characterized by the presence of a large amount of unprocessed OVA surrounded by dermal inflammatory infiltrate, suggesting defective activity of antigen‐presenting cells. Together, these findings supported our hypothesis that the poor antigen clearance in vivo may be related to the impaired macrophage function in vitro. These observations in the murine experimental model may reflect some of the consequences of EtOH consumption by humans.

Malondialdehyde–Acetaldehyde‐Adducted Surfactant Protein Alters Macrophage Functions Through Scavenger Receptor A

“…A significant reduction in superoxide ion and nitrite ion release was observed when RAW 264.7 macrophages were exposed to SPD‐MAA. Alcohol has been previously reported to reduce phagocytic function, antimicrobial activity, superoxide ion, and nitric oxide release from macrophages (Andrade et al., ; Castro et al., ; D'Souza et al., ; Libon et al., ; Satapathy and Shrivastava, ; Szabo, ). Our findings may suggest MAA adduct formation could be one of the mechanisms through which alcohol may exert such actions.…”

Previous Ingestion ofLactococcus lactisby Ethanol-Treated Mice Preserves Antigen Presentation Hierarchy in the Gut and Oral Tolerance Susceptibility

“…Previous reports from our group demonstrated that high-dose ethanol (EtOH) administration is able to induce an allergic-type inflammatory response in function of enhanced levels of seric IgE, high levels of gastric interleukin (IL)-4 and increased IL-4 synthesis by splenic T cells after in vitro unspecific stimulus (concanavalin A) (Andrade et al, 2006(Andrade et al, , 2008(Andrade et al, , 2009). This allergic-type reaction in the GALT can disturb pathways involved in the establishment of regulatory mechanisms, hindering oral tolerance.…”

Short‐term Administration of Ethanol in Mice Deviates Antigen Presentation Activity Towards B Cells

“…Previous reports from our group described a reliable model of acute high‐dose alcohol consumption (4.5 mg/kg during 4 consecutive days) and showed that ethanol affects several immunological functions [14, 15]. Our data demonstrated that changes on macrophage functions, including phagocytic capacity, inflammatory cytokine synthesis and NO production, can be observed as early as 24 h after high‐dose short‐term ethanol administration and that they are maintained for up to 30 days thereafter [15].…”

“…We have reported that short‐term administration of high doses of ethanol induce an allergy‐like immune profile in C57BL/6 mice [14] and had a negative impact in the phagocytic capacity of peritoneal macrophages [15]. Herein, using the same model, we focused our investigation on the effects of alcohol in the antigen‐presenting ability of ‘classical’ APC such as macrophages, DC and B cells.…”

“…Three days later, peritoneal cell suspension was collect as described by Andrade et al. (2008) [15]. Briefly, animals were killed by cervical dislocation, i.p.…”