Fitness-related Differences In The Polarization Of Lipid-exposed Macrophages Following Acute Exercise

Abstract

Compared to anti-inflammatory M2 (CD206+) macrophages, pro-inflammatory M1 (CD86+) macrophages are considered to be highly atherogenic. Increased cardiovascular fitness is linked to attenuated atherosclerotic plaque formation as well as anti-inflammatory alterations in the immune cells that mediate this process. Therefore, macrophage polarization in unfit individuals may differ from that of fit individuals following exposure to physical stress and elevated lipids. PURPOSE: To determine fitness-related differences in the polarization of lipid-exposed macrophages following acute, moderate-intensity exercise. METHODS: 8 fit (VO2 peak; M: ≥ 45 mLO2/kg/min, F: ≥ 35 mLO2/kg/min) and 12 unfit (VO2 peak; M: < 40 mLO2/kg/min, F: < 30 mLO2/kg/min) male and female subjects performed 30 minutes of moderate-intensity (60% VO2 peak) cycling. Blood samples were collected pre-exercise (PRE) and immediately- (POST), 1 hour- (1HR), and 2-hours (2HR) post-exercise. Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation, and adherent monocytes were cultured with LDL (150 mg/dL) and palmitate (10ug/mL) for 4 hours. Cells were washed and cultured with 20% autologous serum for 7 days. The resulting macrophages were subsequently stained with antibodies against CD86 and CD206 for flow cytometric analysis. A mixed between-within ANOVA was performed to determine differences in receptor expression between groups (fitness) and within subjects (time). RESULTS: A mixed between-within ANOVA found no significant between-subjects main effects for CD86 (p=0.667) and CD206 (p=0.675) macrophage expression. A main effect of time was significant for the expression of CD206 (p=0.033). A profile plot suggests that CD206 expression was different between fitness groups PRE, POST, and 1HR. CONCLUSION: Macrophage expression of CD206 was observed to be different between fit and unfit individuals immediately before and following an acute bout of moderate-intensity exercise and lipid exposure. Alterations in “M2” macrophage polarization may contribute to cardiovascular risk in unfit individuals.