Intracellular mechanisms responsible for exercise-induced suppression of macrophage antigen presentation

• Published in: Journal of applied physiology (1985) Vol. 88; no. 2; pp. 804 - 810
• Main Authors: Ceddia, M. A, Voss, E. W., Jr, Woods, J. A
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Physiological Soc 01.02.2000; American Physiological Society
• Subjects: Animals; Antigen Presentation; Antigen-Presenting Cells - cytology; Antigen-Presenting Cells - immunology; Biological and medical sciences; Chickens; Coculture Techniques; Culture Media, Conditioned - chemistry; Dose-Response Relationship, Drug; Exercise; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immune system; Immunobiology; Interleukin-2 - metabolism; Macrophages, Peritoneal - cytology; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - immunology; Male; Mice; Mice, Inbred BALB C; Modulation of the immune response (stimulation, suppression); Ovalbumin - immunology; Ovalbumin - metabolism; Ovalbumin - pharmacology; Peptides; Physical Conditioning, Animal - physiology; Specific Pathogen-Free Organisms; T-Lymphocytes - cytology; T-Lymphocytes - drug effects; T-Lymphocytes - metabolism; Physical exercise; Antigenic determinant; Immunomodulation; Rodentia; Stress; Antigen; Vertebrata; Mammalia; Mouse; Intracellular; Macrophage; Peritoneum; Immune system
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/jappl.2000.88.2.804

Physical Fitness Research Laboratory, 1  Department of Kinesiology and 2  Department of Microbiology, University of Illinois, Urbana, Illinois 61801 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 (~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 (~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. antigenic peptide generation; immune; mice; stress