Platelet-Derived Growth Factor-D Activates Complement System to Propagate Macrophage Polarization and Neovascularization

• DOI: 10.3389/fcell.2021.686886
• Publication Date: 2021-06-02T11:12:56Z
• Authors: Zhen Xiong; Qianqian Wang; Wanhong Li; Lijuan Huang; Jianing Zhang; Juanhua Zhu; Bingbing Xie; Shasha Wang; Haiqing Kuang; Xianchai Lin; Chunsik Lee; Anil Kumar; Xuri Li
• Keywords: Macrophage polarization; Platelet-derived growth factor

Platelet-derived growth factor-D (PDGF-D) is highly expressed in immune cells. However, the potential role of PDGF-D system remains thus far unclear. Here, we reveal a novel function activating both classical and alternative complement pathways that markedly increase chemokine cytokine responses to promote macrophage polarization. Pharmacological targeting C3a receptor using SB290157 alleviated PDGF-D-induced neuroinflammation by blocking polarization inhibited pathological choroidal neovascularization. Our study suggests therapeutic strategies may open up new possibilities for treatment neovascular diseases.