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Effect of acute treadmill exercise on LFA-1 antigen expression in murine splenocytes
1Department of Health Studies and Gerontology, Faculty of Applied Health Sciences, University of Waterloo, Ontario, Canada.
Insights
Acute exercise impacts natural killer cell activity by reducing the effectiveness of LFA-1 blockade, potentially altering tumor cell killing. This study investigated exercise effects on CD11a (LFA-1) activity in NK cells.
Area of Science:
- Immunology
- Exercise Physiology
- Cellular Biology
Background:
- The LFA-1 molecule (CD11a/CD18) is crucial for cell-mediated cytotoxicity, particularly involving natural killer (NK) cells and their interactions with target cells.
- Understanding how physiological stressors like acute exercise influence immune cell function, specifically NK cell-mediated cytotoxicity, is important for immune response research.
Purpose of the Study:
- To investigate the effect of acute exercise on the activity of CD11a (LFA-1) on NK cells.
- To determine if exercise alters the susceptibility of NK cell-mediated cytotoxicity to LFA-1 blockade.
Main Methods:
- Murine splenocytes were analyzed before and at various time points after acute treadmill exercise.
- Natural killer cell activity (NKCA) was assessed using a 51Cr release assay with tumor target cells.
- The role of LFA-1 was evaluated by adding anti-CD11a monoclonal antibody (mAb) to effector:target cell suspensions.
Main Results:
- Antibody blockade of LFA-1 significantly reduced tumor cell lysis in both fresh and IL-2 augmented splenocytes.
- Acute exercise significantly affected the cytolytic activity of fresh splenocytes, with changes observed between 30 and 120 minutes post-exercise.
- The inhibitory effect of anti-CD11a antibody on cytotoxicity was lowest at 30 minutes post-exercise, suggesting reduced LFA-1 dependence.
Conclusions:
- Acute exercise appears to make mouse splenocytes more resistant to LFA-1 blockade.
- This altered resistance to LFA-1 blockade may influence the killing of tumor target cells in vitro following exercise.
Abstract:
The LFA-1 intercellular adhesion molecule (ICAM), expressed on human and murine CD8+ and natural killer (NK) cells, participates in cytolytic interaction with target cells. This study was designed to determine whether acute exercise alters the activity of CD11a (LFA-1) on NK cells. Fourty male C3H/HeNHSD mice were sacrificed before (sedentary) or at various time points after acute treadmill exercise (30 m/min, 4 degrees slope, 30 minutes). Splenic natural killer cell activity (NKCA) was determined using a standard 51Cr release assay, using fresh splenocytes or splenocytes which had been incubated for 3 days with 100 U rIL-2. 10 micrograms/ml of mAb to LFA-1(anti-CD11a) or an equal volume of culture medium were added to the effector:target suspensions prior to 4.5 h incubation. There was a significant main effect of antibody treatment on cytolysis of tumour targets by fresh and IL-2 augmented splenocytes (p < 0.001); for both fresh and IL-2 augmented splenocytes, addition of anti-CD11a antibody reduced cytolysis of tumour target cells. Further, there was a significant main effect of exercise on fresh (p < 0.01) but not IL-2 augmented splenocytes cytolysis; this effect was due to differences in cytolytic activity between 30 and 120 minutes post exercise. Calculation of delta% in cytotoxicity showed that the capacity of mAb to CD11a to inhibit cytolysis was the lowest at 30 minutes after exercise (25%). The delta% in cytotoxicity was less pronounced in samples obtained from IL-2 augmented splenocytes, irrespective of timing of exercise. These results suggest that acute exercise renders mouse splenocytes more resistant to the blockade effect of anti--CD11a (LFA-1) and, as result, may alter killing of tumour target cells in vitro.
