Gangliosides enhance M2-polarized macrophage elongation induced by IL-4 and IL-13
Gangliosides enhance M2-polarized macrophage elongation induced by IL-4 and IL-13
MESHRAM SNEHAL CHANDRAKANT(부산대학교); Choi Hee-Jin(Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Korea); Cho Minkyoung(Department of Parasitology and Tropical Medicine, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Korea); Shim Jaewon(Department of Biochemistry, Kosin University College of Medicine, Busan 49267, Republic of Korea); Ha Ki-Tae(Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Korea); Bae Sung-Jin(Department of Molecular Biology and Immunology, Kosin University College of Medicine, Busan 49267, Republic of Korea)
40권 3호, 188~198쪽
초록
Background: Macrophage polarization plays a crucial role in the immune response, and gangliosides regulate macrophage function. In this study, we investigated the role of gangliosides in modulating macrophage morphology and function in response to M2 polarization induced by interleukin (IL)-4 and IL-13.Methods: The mouse monocyte/macrophage cell line RAW264.7 and bone marrow macrophages were used to assess the role of gangliosides in macrophages. Additionally, St3gal5 knockdown was achieved using small interfering RNA constructs for further examinations.Results: Elongation of M2-polarized macrophages in the presence of IL-4 and IL-13 was associated with increased ganglioside synthesis, as shown by reverse transcription-polymerase chain reaction and immunoblot analyses. Pretreatment with D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol and St3gal5 knockdown significantly reduced elongation, indicating that gangliosides play a substantial role in this process. Flow cytometry revealed that ganglioside monosialodihexosylganglioside (GM3) and ganglioside disialodihexosylganglioside (GD3) expression was significantly upregulated in M2-polarized macrophages. Moreover, transwell migration assays demonstrated that GM3 promoted macrophage migration, and this effect was abrogated by St3gal5 knockdown. Despite increased elongation and migration, phagocytic activity was reduced in elongated macrophages, as measured by the phagocytosis index using latex beads, which was reversed upon St3gal5 knockdown. Additionally, GM3 treatment activated the protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) signaling pathways, as confirmed by immunoblot analysis, demonstrating their role in ganglioside-induced elongation.Conclusions: Our findings highlight the crucial role of gangliosides in regulating the morphological plasticity of macrophages via AKT and ERK activation to promote elongation, which results in increased migration and reduced phagocytosis. This study provides insights into the mechanism by which gangliosides influence macrophage function and immune responses.
Abstract
Background: Macrophage polarization plays a crucial role in the immune response, and gangliosides regulate macrophage function. In this study, we investigated the role of gangliosides in modulating macrophage morphology and function in response to M2 polarization induced by interleukin (IL)-4 and IL-13.Methods: The mouse monocyte/macrophage cell line RAW264.7 and bone marrow macrophages were used to assess the role of gangliosides in macrophages. Additionally, St3gal5 knockdown was achieved using small interfering RNA constructs for further examinations.Results: Elongation of M2-polarized macrophages in the presence of IL-4 and IL-13 was associated with increased ganglioside synthesis, as shown by reverse transcription-polymerase chain reaction and immunoblot analyses. Pretreatment with D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol and St3gal5 knockdown significantly reduced elongation, indicating that gangliosides play a substantial role in this process. Flow cytometry revealed that ganglioside monosialodihexosylganglioside (GM3) and ganglioside disialodihexosylganglioside (GD3) expression was significantly upregulated in M2-polarized macrophages. Moreover, transwell migration assays demonstrated that GM3 promoted macrophage migration, and this effect was abrogated by St3gal5 knockdown. Despite increased elongation and migration, phagocytic activity was reduced in elongated macrophages, as measured by the phagocytosis index using latex beads, which was reversed upon St3gal5 knockdown. Additionally, GM3 treatment activated the protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) signaling pathways, as confirmed by immunoblot analysis, demonstrating their role in ganglioside-induced elongation.Conclusions: Our findings highlight the crucial role of gangliosides in regulating the morphological plasticity of macrophages via AKT and ERK activation to promote elongation, which results in increased migration and reduced phagocytosis. This study provides insights into the mechanism by which gangliosides influence macrophage function and immune responses.
- 발행기관:
- 고신대학교 의과대학 학술지
- 분류:
- 의학일반