RESUMEN
Extracellular substances, including membrane-impermeable nutrients, are taken up by cells via endocytosis. Endocytosis is also an important pathway for antigen uptake by antigen-presenting cells such as monocytes, macrophages, dendritic cells, and B cells. In this study, we investigated the regulatory mechanism of endocytosis in THP-1 cells, a monocytic leukemia cell line. We analyzed the effect of IgG and insulin, which are abundant in the serum and play important roles in immunity and metabolism, respectively, on the endocytic activity in THP-1 cells. The results indicated that IgG and insulin enhance pinocytosis and phagocytosis via activation of phosphatidylinositol 3-kinase (PI3K). Our results suggest that IgG and insulin contribute to the maintenance of endocytic activity and are important for antigen presentation and nutrient uptake.
Asunto(s)
Fosfatidilinositol 3-Quinasa , Fosfatidilinositol 3-Quinasas , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Insulina , Células THP-1 , Endocitosis , Monocitos/metabolismo , Inmunoglobulina GRESUMEN
Mechanistic/mammalian target of rapamycin complex 1 (mTORC1) is a serine/threonine kinase that plays a major role in cell metabolism. Although mTORC1 inhibitors are known to exert immunosuppressive effects, their effects on immune cells are not fully understood. In the present study, we examined the involvement of mTORC1 in the differentiation and functions of macrophages using THP-1 cells, which are derived from human monocytic leukemia and differentiate into macrophage-like cells upon treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). We also examined the effects of two mTOR inhibitors, Torin 1 and rapamycin, on TPA-stimulated THP-1 cells. Although mTORC1 activation was observed upon TPA stimulation, mTOR inhibitors did not affect TPA-induced morphological changes or expression of the general macrophage marker, CD11b. In contrast, phagocytosis and fluid endocytosis were significantly impaired by the mTOR inhibitors. Endocytosis suppression was observed when mTOR inhibitors were added during differentiation, but not before or after differentiation, suggesting that endocytosis suppression altered the direction of differentiation. Furthermore, mTOR inhibitors altered the expression of M1/M2 polarization markers. These results suggest that the immunosuppressive effects of mTOR inhibitors may involve the suppression of macrophage endocytosis caused by abnormal cell differentiation.