Modulation of NLRP3 Inflammasome Activity in Subtype Differentiation of THP-1 Cells after Phagocytosis of Aged Erythrocyte
Objective To clarify whether NLRP3 inflammasome can modulate macrophage phagocytic capacity towards red blood cells(RBCs)and regulate macrophage subtype polarization.Methods THP-1 cells with low expression of NLRP3(ID3 THP-1),cells transfected with an empty vector(shNC THP-1),and wild-type THP-1 cells were used as macrophage models.These cells were incubated with untreated RBCs,water bath-aged RBCs,and IgG-opsonized RBCs,respectively.Flow cytometry was used to detect the phagocytic rate of THP-1 cells to different RBC types and to measure the expression of M1 subtype markers(CD16 and CD86),and M2 subtype markers(CD163 and CD206)on THP-1 cells.Results 1D3 THP-1 with reduced NLRP3 expression exhibited significantly downregulated phagocytic capacity towards RBCs.Aged RBCs induced the differentiation of THP-1 cells into the M1 subclass while inhibiting their differentiation into the M2 subclass.Decreased expression of the NLRP3 inflammasome in THP-1 cells led to a downregulation of their ability to differentiate into the M1 subclass following RBC phagocytosis,accompanied by their enhanced capacity to differentiate into the M2 subclass.Conclusion NLRP3 inflammasome can serve as a pivotal regulatory target,governing macrophage phagocytosis of RBCs and their subsequent subclass differentiation.