title: Role of Kir2.1 in human monocyte-derived foam cell maturation.
abstract: 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.
authors.affiliation: Department of Neonatology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Xin-Jun
authors.initials: XJ
authors.lastname: Lei
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Wang
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Dong-Qi
authors.initials: DQ
authors.lastname: Wang
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.|Key Laboratory of Environment and Gene Related to Diseases of Ministry of Education, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Zu-Yi
authors.initials: ZY
authors.lastname: Yuan
mesh_terms: D000328:Adult; D002454:Cell Differentiation; D002460:Cell Line; D048430:Cell Shape; D005487:Foam Cells / Q000502:physiology*; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D008564:Membrane Potentials; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D051116:Receptors, Scavenger / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: C489457:KCNJ2 protein, human; D024661:Potassium Channels, Inwardly Rectifying; D051116:Receptors, Scavenger
keywords: atherosclerosis; foam cells; macrophages; monocytes; potassium channels