High mobility group box 1 skews macrophage polarization and negatively influences phagocytosis of apoptotic cells

高迁移率族蛋白 B1 扭曲巨噬细胞极化并对凋亡细胞的吞噬作用产生负面影响

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作者:Fleur Schaper, Karina de Leeuw, Gerda Horst, Hendrika Bootsma, Pieter C Limburg, Peter Heeringa, Marc Bijl, Johanna Westra

Conclusion

Circulating monocytes from SLE patients display an M1-like phenotype compared with HCs, but in vitro differentiation abolishes this difference. HMGB1 skews differentiation of M2-like macrophages towards an M1-like phenotype and, subsequently, reduces phagocytosis of apoptotic cells. These data imply that the phenotype of monocytes or macrophages is determined by their environment, such as the presence of cytokines and HMGB1.

Methods

SLE patients with quiescent disease (SLEDAI ⩽4) and healthy controls (HCs) were included. Monocytes and differentiated M1 and M2 macrophages were assessed for expression of M1 and M2 markers and for phagocytic capacity. HMGB1 was added during differentiation and during phagocytosis.

Results

Expression of CD86 (M1) was not different, whereas CD163 (M2) was significantly lower on SLE monocytes. After differentiation, no differences regarding surface receptor expression and phagocytic capacity were observed between M1 and M2 macrophages from SLE patients and HCs. Addition of HMGB1 during M2 differentiation resulted in high IL-6 and TNF-α mRNA expression and reduced phagocytic capacity of apoptotic cells. Furthermore, adding HMGB1 to apoptotic Jurkat cells diminished phagocytosis of these cells.

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