title: Intracellular mechanisms responsible for exercise-induced suppression of macrophage antigen presentation.
abstract: In a previous study, we demonstrated that exhaustive exercise suppressed peritoneal macrophage antigen presentation (AP). In this study, we explored the intracellular mechanism(s) responsible for this suppression. Pathogen-free male BALB/c mice (8 +/- 2 wk) were randomly assigned to either home cage control (HCC) or exhaustive exercise stress (Exh, 18-30 m/min for 3 h/day) treatment groups. The mice underwent treatments for a period of 4 days during induced peritoneal thioglycollate inflammation. Elicited macrophages were harvested, purified, and incubated with chicken ovalbumin (C-Ova, 2. 5 and 10 mg/ml) for 18 h. After macrophages were washed, they were cocultured with C-Ova-specific T cells for 48 h at which time the supernates were harvested and analyzed via ELISA for interleukin (IL)-2 as an indication of macrophage AP. There was no significant (P > 0.05) difference in macrophage AP between cells fixed with paraformaldehyde vs. those that remained unfixed, suggesting that Exh did not affect production of soluble factors influencing macrophage AP (i.e., IL-1, IL-4, PGE(2)). The ability of macrophages to generate C-Ova immunogenic peptides was analyzed using FITC-labeled C-Ova, which shows fluorescence only when degraded intracellularly. There was a significant ( approximately 20%, P < 0. 05) suppression in fluorescence in the Exh compared with HCC, indicating a possible defect in the ability of macrophages from Exh to degrade C-Ova into immunogenic peptides. Macrophages were also incubated with C-Ova immunogenic peptide in a manner identical to that for native C-Ova. We found a similar suppression ( approximately 22-38%, P < 0.05) in macrophage AP using a C-Ova peptide when compared with native C-Ova in the Exh group, indicating reduced major histocompatibility complex (MHC) II loading and/or C-Ova-MHC II complex cell surface expression. In conclusion, these data indicate an intracellular defect in the macrophage antigen processing pathway induced by Exh.
authors.affiliation: Physical Fitness Research Laboratory, University of Illinois, Urbana, Illinois 61801, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Ceddia
authors.forename: E W
authors.initials: EW
authors.lastname: Voss
authors.forename: J A
authors.initials: JA
authors.lastname: Woods
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology; D002645:Chickens; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D007376:Interleukin-2 / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D007376:Interleukin-2; D010047:Ovalbumin