Biomedical subjects

M A Ceddia

Publications and source records attributed to M A Ceddia.

9 recordsLinked to original sources

PubMed2003

Exercise training increases the näive to memory T cell ratio in old mice.

Aging is associated with changes in T cells including involution of the thymus gland and an imbalance in the proportion of näive (CD44lo) and memory (CD44hi) T cells in the periphery. Reversal of these changes may improve immunity in the aged. We sought to determine whether 4 months of moderately intense treadmill running (EXC; 5 days/week, 45 min/day, 13-22 m/min) in 2 month (Y) and 18 month (O) old male Balb/c mice would alter T lymphocyte profiles in the thymus and spleen when compared to sedentary controls (CON). Splenocytes and thymocytes were harvested 24-48 h after the last exercise session and analyzed using immunofluorescence and flow cytometry. While there were significant age-related changes (lower cell number, altered subsets) in the thymuses of O when compared to Y mice, exercise training failed to affect any of these measures in mice of either age. Aged mice exhibited a significantly (p < .05) higher percentage of splenic memory cells and a lower percentage of näive cells in both the CD4 and CD8 T cell subsets. Interestingly, exercise training significantly (p < .05) increased the percentage of näive and decreased the percentage of memory cells in both the CD4+ (69.6+/-1.7% näive and 30.4+/-1.7% memory for OCON vs. 75.0+/-1.5% näive and 25.0+/-1.5% memory in OEXC) and CD8+ (60.0+/-2.6% näive and 40.0+/-2.6% memory in OCON vs. 76.7+/-2.7% näive and 23.3+/-2.7% memory in OEXC) T cells subsets in O, but not Y, mice. This effect was due to a decrease in the absolute number of memory cells and not an increase in the absolute number of näive cells. We conclude that 4 months of EXC has little restorative effect on the thymus in aged mice, but can restore the percentages of näive and memory cells in the spleen towards that of young mice, perhaps due to removal of memory cells.

Aging↗

PubMed2000

Special feature for the Olympics: effects of exercise on the immune system: exercise-induced modulation of macrophage function.

Macrophages are important effector cells involved in phagocytosis, microbial killing and antitumour activity. Macrophages also display accessory cell function, in that they can present antigen to foster the development of T lymphocyte-mediated immunity. Recent work, including studies from this group, has demonstrated that acute and chronic exercise can affect many facets of macrophage biology. Manifestation of these effects depends on exercise intensity and duration, the function measured, the timing of measurement in relation to exercise and the concentration of the macrophage-activating stimulus. Exercise has potent stimulatory effects on phagocytosis, antitumour activity, reactive oxygen and nitrogen metabolism, and chemotaxis. Indeed, it has been shown that exercise training can increase macrophage antitumour activity in mice of different ages. However, not all functions are enhanced by exercise. Exercise-induced reductions in macrophage MHC II expression and antigen-presentation capacity have been documented. These findings bring up the possibility that exercise, and perhaps other stressors, activate macrophages for effector functions while downregulating accessory cell functions. To a large extent, the mechanisms responsible for the exercise-induced changes in macrophage function remain unknown, but may depend on exercise-induced changes in neuroendocrine factors. Future studies need to explore the effects in a mechanistic way and provide documentation as to their physiological significance.

Animals↗

PubMed2000

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

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.

Animals↗

PubMed1999

Effects of 6 months of moderate aerobic exercise training on immune function in the elderly.

The purpose of this study was to determine the effects of 6 months of moderate aerobic exercise on age-dysregulated measures of T lymphocyte and natural killer (NK) cell number and function. Previously sedentary elderly (age = 65 +/- 0.8 years) subjects were randomly assigned to supervised 3 time/week exercise intervention group (EXC, n = 14) or flexibility/toning control group (FT-CON, n = 15). Fasting resting blood samples were drawn prior to and after the 6 month intervention. The EXC group exhibited a significant (P < 0.05) 20% increase in VO2 max, whereas the FT-CON group had a smaller non-significant (P = 0.07) increase (9%). Immune results revealed that, in general, changes in immune function in response to 6 months of exercise training at an average intensity of 52% heart rate reserve (HRR) were similar when compared to FT-CON who exercised at approximately 21% HRR. There were no intervention-induced changes in total white blood cell, neutrophil, lymphocyte, monocyte, eosinophil, or basophil blood counts. Furthermore, the percentage and number of CD3+, CD4+ and CD8+ T cells in the blood remained unchanged. There was a tendency for the percentage and number of CD4+ and CD8+ näive cells (CD45RA+) to increase and for CD4+ memory cells (CD45RO+) to decrease post-intervention, especially in FT-CON. Both groups exhibited a small intervention-induced increase in the T-cell proliferative response to mitogenic stimulation: the percentage change of which was higher in the EXC group at several doses of Con A. Unstimulated NK cell cytolysis versus K562 cells tended to increase (P < 0.1) in the EXC group with little change in FT-CON. We conclude that 6 months of supervised exercise training can lead to nominal increases in some measures of immune function, while not affecting others, in previously sedentary elderly.

Aged↗

PubMed1999

Differential leukocytosis and lymphocyte mitogenic response to acute maximal exercise in the young and old.

UNLABELLED: Despite the increasing use of exercise in the elderly as a means of improving muscle function, little is known regarding the effects of exercise on the senescent immune system. PURPOSE: The purpose of this study was to determine the effects of acute maximal exercise on blood leukocyte numbers, leukocyte subsets, and the T cell mitogenic response in the elderly. METHODS: Previously sedentary elderly (N = 33, 65.3 +/- 0.8 yr) and young (N = 14, 22.4 +/- 0.7 yr) subjects participated in a modified Balke maximal exercise treadmill test. Venous blood samples were collected pre-, immediately post-, and 20 min postexercise. Blood was analyzed for leukocyte counts, leukocyte subsets via immunofluorescence, and whole blood mitogenesis in response to various doses of mitogens. RESULTS: Whereas VO2max was lower in the elderly, maximal RQ, age-predicted heart rates, and times to fatigue were not different, indicating that both groups achieved relative maximal exercise intensity. There were significant exercise-induced leukocytoses in both the elderly and young made up largely of a lymphocytosis and neutrophilia. The magnitude of the leukocytosis was lower in the elderly and failed to return to pre-exercise levels by 20 min postexercise. Acute maximal exercise increased CD8+ (153% vs 112% in young and old, respectively) and CD4+ (57% vs 22% in young and old, respectively) T cells when measured immediately postexercise. By 20 min postexercise, concentrations in the young were not significantly different from baseline, whereas CD8 cell number was still elevated in the old. The elderly had significantly higher percentages of memory (i.e., CD45RO+) and significantly lower percentages of naive (i.e., CD45RA+) CD4 and CD8 T cells pre-exercise, and the young and old recruited approximately equal numbers of CD8+ naive and memory cells to the blood in response to exercise. In contrast, the aged recruited significantly fewer numbers of CD4+ naive and transitional (CD45RA+RO+) cells. At most doses of Con A and PHA, the lymphoproliferative response was lower in the elderly subjects even though they had significantly higher numbers and percentages of CD3+ cells. Interestingly, immediately postexercise, young (but not old) subjects demonstrated reduced proliferative ability on a per CD3+ cell basis. CONCLUSIONS: These data indicate that several blood leukocyte responses to maximal exercise stress are similar in the young and the old. However, the elderly demonstrate a less resilient leukocytosis and a different lympho-proliferative response following acute maximal exercise.

Adult↗

PubMed1999

Chronic exercise increases macrophage-mediated tumor cytolysis in young and old mice.

In this study, we determined the effects of age and chronic treadmill running (16 wk; 5 days/wk; 45 min/day; 18-22 m/min) on resident peritoneal macrophage responsiveness to interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) in young (6 mo) and aged (22 mo) male BALB/cByJ mice by measuring cytolytic ability and production of reactive nitrogen products. Macrophages (>90% Mac-3(+)) were incubated with various concentrations of IFN-gamma and LPS for 24 h. After washing, P815 tumor cells were utilized as targets in a 16-h 51Cr release assay. We found that aging resulted in a significant reduction in the ability of macrophages to respond to the highest doses of IFN-gamma and LPS and kill P815 cells (46 +/- 4 vs. 34 +/- 2% in young and old mice, respectively). Exercise training significantly increased macrophage cytolysis in both age groups (66 + 7 vs. 44 + 2% in young and old mice, respectively); this effect was larger in the young mice. Macrophages from young exercised mice also produced significantly (50-60%) more NO-2; there was a tendency for higher NO-2 in old exercisers. The inducible nitric oxide synthase (iNOS) inhibitor NG-monomethyl-L-arginine (L-NMMA) significantly reduced macrophage cytolysis and NO-2 production and completely abrogated exercise-induced increases in these measures. RT-PCR analysis revealed significantly higher iNOS mRNA levels in macrophages obtained from the exercise-trained mice and significantly lower iNOS mRNA in old compared with young mice. We conclude that aging reduces and exercise training increases the capacity of resident peritoneal macrophages to respond to IFN-gamma and LPS with increased tumor cytolysis. Enhanced iNOS gene expression and NO-2 production are likely the contributing mechanisms of the exercise-induced enhancement of cytolysis in young mice. While L-NMMA did block the exercise-induced increase in cytolysis, exercise did not increase NO-2 or iNOS gene expression in the old mice, indicating perhaps the contribution of other cytolytic mechanisms in old mice.

Animals↗

PubMed1999

Exercise suppresses macrophage antigen presentation.

This study determined the effects of exercise on the ability of macrophages (Mphi) to present antigen to T cells. Pathogen-free male Balb/c mice (8 +/- 2 wk of age) were randomly assigned to either home cage control, moderate exercise (Mod; 18 m/min, 5% grade, 0.5 h/day), exhaustive exercise (Exh, 18-30 m/min, 3 h/day), or treadmill control groups. The mice underwent treatments for 4 days during peritoneal thioglycolate inflammation. Peritoneal Mphi were harvested, purified, and incubated with chicken ovalbumin (C-OVA; 0-10 mg/ml) for 18 h. Mphi were then cocultured with C-OVA-specific T cells for 48 h, and the supernatants were analyzed via ELISA for interleukin-2 as an indication of Mphi antigen presentation (AP). Exh exhibited suppressed ( approximately 25-34%) Mphi AP across a wide range of C-OVA doses when measured immediately, 3, and 24 h postexercise. In contrast, Mod had reduced Mphi AP only at 3 h postexercise. Mphi AP was also lower in the treadmill control (4-27%) compared with the home cage control group, but was significantly higher than Exh. The reduction in Mphi AP was not due to exercise-induced differences in Mphi number, percentage, or expression of intercellular adhesion molecule-1, B7-2, or major histocompatability complex II, molecules important in AP. In conclusion, our data lend evidence that may help explain the increased incidence of infection observed after prolonged exhaustive exercise or overtraining.

Animals↗

PubMed1998

Effects of maximal exercise on natural killer (NK) cell cytotoxicity and responsiveness to interferon-alpha in the young and old.

We investigated the effects of a graded maximal exercise treadmill test on natural killer (NK) cell number, activity, and responsiveness to interferon-alpha (IFN-alpha) in young (22+/-0.7 yrs) and elderly (65+/-0.8 yrs) sedentary subjects. NK cell cytotoxicity (NKCC) was determined using Ficoll purified peripheral blood mononuclear cells (PBMCs) by a 51Cr release assay against NK-sensitive (K562) and NK-insensitive (Daudi) target cells at various effector:target (E:T) ratios before and immediately after exercise. PBMCs were incubated with rhu IFN-alpha (125 and 250u/10(6) PBMCs) or without for 2 hrs before addition to the 51Cr release assay. There were no differences in unstimulated NKCC against K562 or Daudi targets between the old and the young despite significantly (p=.01) higher percentages of CD56+ NK cells (21.1+/-2.3% in old vs 12.5+/-2.5% in young, pre-exercise). IFN-alpha increased NKCC versus both targets, and NK cells from old subjects were hyporesponsive to IFN-alpha stimulation; this was especially evident at low E:T ratios versus Daudi cells. Maximal exercise significantly increased (50-200%) unstimulated NKCC versus K562 and Daudi targets similarly in both young and old and increased the percentage of CD56+ cells in the PBMC fraction to 33.3+/-3.7% and 23.3+/-3.6% in old and young, respectively. We found a significant correlation between %CD56+ and basal NKCC versus K562s and Daudi cells in the young (i.e., r=.55; p=.02 vs K562s), but not the old (i.e., r=.20; p=.29 vs K562s) subjects. This indicates that, in the young, part of the exercise-induced increase in NKCC is due to an increase in NK cell number. Maximal exercise did not affect unstimulated per cell killing of K562s, but tended to increase per cell killing of Daudis. These results indicate that CD56+ cells from old subjects have an intrinsic defect in their ability to perform cytolysis and respond to IFN-alpha. Furthermore, a single bout of maximal exercise increases NKCC and CD56+ cell number similarly in both young and old subjects regardless of the target cell used.

Adolescent↗

PubMed1997

Effects of exercise on the macrophage MHC II response to inflammation.

The purpose of this investigation was to determine the effects of different doses of exercise on the ability of Propionibacterium acnes (P. acnes) to induce major histocompatibility complex (MHC) II antigen expression on macrophages (M phi's). Pathogen-free male Balb/c mice were exercised on a treadmill moderately (MOD, 15-17 m/min, 5% grade, 30 min/day) or exhaustively (EXH, 15-40m/min, 5% grade, 2-4hr/day) for a period of 7 days during P. acnes-induced inflammation. A control group (CON) consisted of animals exposed to the treadmill environment and handling. Sub-optimal (0.03 mg/g b.wt., i.p.) and optimal (0.08 mg/g b.wt.) doses of P. acnes were used to increase M phi MHC II expression. Animals were sacrified on Day 7 and M phi's were harvested by peritoneal lavage. Direct immunofluorescent staining was performed by incubating peritoneal exudate cells (10[6]) with an FITC-labeled anti-mouse MHC II (I-A[d]) antibody. Basal expression of MHC II was not affected by exercise. There were no significant differences among the groups in the percentage of M phi's expressing MHC II at any dose of P. acnes. However, EXH significantly (p < 0.05) suppressed the expression (mean fluorescent intensity, MFI) of MHC II when compared to MOD (37.1+/-1.95 [mean+/-sem] vs 49.1+/-2.15, p < 0.05) at the suboptimal P. acnes dosage. At the optimal P. acnes dose, both MOD and EXH significantly suppressed (27+/-1.6, 25+/-2.2 and 41.5+/-3.2, for EXH, MOD, and CON, respectively, p<0.0001) P. acnes-induced M phi MHC II MFI. Plasma corticosterone was highly (r=-0.71, p = 0.001) inversely correlated with M phi MHC II expression. However, exercise failed to affect P. acnes-induced production of interferon-gamma. These data suggest that, dependent on the degree of stimulation, exercise can negatively affect M phi expression of MHC II, an effect that may be detrimental to the M phi's ability to present antigen to T lymphocytes.

Animals↗