Kv1.3 channel blockade enhances the phagocytic function of RAW264.7 macrophages.
1Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking, Union Medical College, Beijing, 100005, China.2Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.3Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking, Union Medical College, Beijing, 100005, China. email@example.com.
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.
Kv1.3 channel; immunoregulation; macrophage activation syndrome; phagocytosis