AUTHOR=Xiong Zhen , Wang Qianqian , Li Wanhong , Huang Lijuan , Zhang Jianing , Zhu Juanhua , Xie Bingbing , Wang Shasha , Kuang Haiqing , Lin Xianchai , Lee Chunsik , Kumar Anil , Li Xuri TITLE=Platelet-Derived Growth Factor-D Activates Complement System to Propagate Macrophage Polarization and Neovascularization JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=9 YEAR=2021 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.686886 DOI=10.3389/fcell.2021.686886 ISSN=2296-634X ABSTRACT=

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