Abstract
This study aimed to comprehend the largely unknown role of voltage-gated potassium channel 1.3 (Kv1.3) in the phagocytic function of macrophages. We found that blocking of the Kv1.3 channel with 100 pmol L(-1) Stichodactyla helianthus neurotoxin (ShK) enhanced the phagocytic capacities of both resting and lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages in the chicken erythrocyte system. In the fluorescein isothiocyanate (FITC)-labeled Escherichia coli k-12 system, ShK increased the phagocytic capacities of resting RAW264.7 cells, but not of the LPS-stimulated cells, as LPS alone stimulated almost saturated phagocytosis of the macrophages. ShK increased the nitric oxide (NO) production in LPS-activated cells, but not in resting RAW264.7 cells. There was no effect of ShK alone on the cytokine secretions in resting RAW264.7 cells, but it suppressed IL-1β secretion in LPS-stimulated RAW264.7 cells. At a concentration of 100 pmol L(-1), ShK did not affect the viability of the tested cells. Kv1.3 was expressed in RAW264.7 cells; this expression was downregulated by LPS, but significantly upregulated by disrupting caveolin-dependent endocytosis with filipin III. In addition, cytochalasin D, an inhibitor of actin polymerization, did not affect the Kv1.3 expression. Thus, blocking of the Kv1.3 channel enhances the phagocytic capacity and NO production of this cell line. Our results suggest that Kv1.3 channel serves as a negative regulator of phagocytosis in macrophages and can therefore be a potential target in the treatment of macrophage dysfunction.
Highlights
Ion channels are expressed in both excitable cells and non-excitable cells
Lei et al [21] reported that blocking of Kv1.3 channel by margatoxin could suppress the transition of mononuclear macrophages to foam cells, which suggested Kv1.3 channel is a therapeutic target of atherosclerosis
The present study focused on the action of Kv1.3 channel in macrophage phagocytosis
Summary
Ion channels are expressed in both excitable cells and non-excitable cells. Compared with those in the excitable cells, the functions of ion channels in the non-excitable cells, such as immune cells, are not well documented. Various ion channels has been reported in macrophages, including Kv1.3 [8], Kv1.5 [8], inwardly rectifying K+ channel 2.1 (Kir2.1) [7], KCa3.1 [9], CRAC [10], transient receptor potential cation (TRPC) channel [11], and voltage-gated proton (hydrogen) channels (HVCN) [12] Among these channels, the Kv channels play a pivotal role in the modulation of macrophage physiology [13]. Our key results demonstrated that selective blockade of Kv1.3 channel could increase the phagocytic capacity of RAW264.7 cells, which suggests that Kv1.3 may serve as a suppresser or negative regulator of macrophage phagocytosis This novel finding can significantly contribute toward the development of therapeutic strategies for diseases involving macrophage malfunction
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