N-desulfated and reacetylated modification of heparin modulates macrophage polarization

Heparin as a widely used anticoagulant drug has potent anti-inflammatory effects, which have been rarely reported to be involved in macrophage polarization. Furthermore, the effects of structural modifications of heparin on the plasticity of macrophage functions have not been clearly understood. In this study, the N-desulfated reacetylated derivative of heparin (NDeSAcH) was prepared and its immunoregulatory effects of macrophage polarization were evaluated. The findings indicated that NDeSAcH could effectively promote the release of more nitric oxide (NO), interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) in RAW264.7 cells than heparin. Moreover, the production of NO, IL-6 and TNF-α was significantly inhibited by NDeSAcH in LPS-induced RAW264.7 cells, while the secretion of transforming growth factor-β (TGF-β) was suppressed in M2 macrophages. The N-desulfated and reacetylated group of heparin was proved to have two-side adjusting effects on the polarization of macrophages. This study suggested that NDeSAcH might be a promising candidate for modulating macrophage polarization and treating inflammation-related diseases.