Sex differences in monocyte CCR2 expression and macrophage polarization following acute exercise

Abstract

Monocyte chemokine receptor 2 (CCR2) and phosphorylated extra-cellular regulated kinase 1 & 2 (ERK1/2) impact macrophage differentiation and progression of atherosclerosis. Whereas aerobic exercise favorably modulates the immune system and reduces atherosclerotic risk, it is unknown whether sex differences exist in the monocyte/macrophage response to acute aerobic exercise.

Aims: To determine the impact of an acute bout of moderate intensity aerobic exercise on monocyte and macrophage CCR2 expression, ERK1/2 phosphorylation, and macrophage polarization in pre-menopausal women and men.

Materials and methods: Blood samples were collected in 24 people (Women/Men; n = 12) prior to (PRE), immediately after a bout of moderate intensity cycle ergometry (POST), and 2 h (2H) following exercise. Monocyte and macrophage CCR2 and phosphorylated ERK1/2 as well as macrophage CD86 and CD206 were analyzed by flow cytometry.

Key findings: PRE classical monocyte CCR2 expression was greater in women compared to men (Women: 20546.2 ± 2306.4 vs. Men: 14437.6 ± 1201.9 AUF; p = 0.028) and was reduced in women at 2H (PRE: 20546.2 ± 2306.4 vs. 2H: 15856.9 ± 1314.4 AUF; p = 0.027). POST classical monocyte CCR2 expression was inversely associated (r = -0.697, p = 0.012) with POST classical monocyte ERK1/2 phosphorylation in women only. The percentage of CCR2⁺ macrophages was lower in women at POST (Women: 62.0 ± 8.9 vs. Men: 83.6 ± 3.1; p = 0.031) and at 2H (Women: 60.3 ± 8.4 vs. Men: 83.5 ± 3.0%; p = 0.016).

Significance: These data suggest that a single bout of moderate intensity aerobic exercise differentially impacts monocyte CCR2 expression and macrophage polarization in women compared to men.

Keywords: Acute exercise; Atherosclerosis; CCR2 expression; Macrophage polarization; Monocyte subsets; Sex differences.