Role of Kir2.1 in human monocyte-derived foam cell maturation

The role of K(+) channels in macrophage immunomodulation has been well-established. However, it remains unclear whether K(+) channels are involved in the lipid uptake of macrophages. The expression and function of the inward rectifier potassium channel (Kir2.1, KCNJ2) in Human acute monocytic leukemia cell line (THP-1) cells and human monocytes derived macrophages (HMDMs) were investigated using RT-PCR and western blotting, and patch clamp technique. The expression of scavenger receptors in THP-1-derived macrophages was detected using western blotting. Expressions of Kir2.1 mRNA and protein in HMDMs were significantly decreased by 60% (P < 0.05) and 90% (P < 0.001) on macrophage maturation, but overexpressed by approximately 1.3 (P > 0.05) and 3.8 times (P = 0.001) after foam cell formation respectively. Concurrently, the Kir2.1 peak current density in HMDMs, mature macrophages and foam cells, measured at -150 mV, were -22.61 ± 2.1 pA/pF, -7.88 ± 0.60 pA/pF and -13.39 ± 0.80 pA/pF respectively (P < 0.05). In association with an up-regulation of Kir2.1 in foam cells, the SR-A protein level was significantly increased by over 1.5 times compared with macrophages (P < 0.05). THP-1 cells contained much less lipids upon Kir2.1 knockdown and cholesterol ester/total cholesterol ratio was 29.46 ± 2.01% (P < 0.05), and the SR-BI protein level was increased by over 6.2 times, compared to that of macrophages (P < 0.001). Kir2.1 may participate in macrophage maturation and differentiation, and play a key role in lipid uptake and foam cell formation through modulating the expression of scavenger receptors.