Department of Dermatology and Venereology, University Hospital of Lausanne UNIL-CHUV, 1011 Lausanne, Switzerland.
Department of Dermatology and Venereology, University Hospital of Lausanne UNIL-CHUV, 1011 Lausanne, Switzerland.
Cell Rep. 2024 Oct 22;43(10):114863. doi: 10.1016/j.celrep.2024.114863. Epub 2024 Oct 11.
Neutrophil cationic proteins (NCPs) are a group of granule antimicrobial and inflammatory proteins released by activated neutrophils. These proteins primarily function via their positively charged structure, which facilitates interactions with bacterial membranes and the formation of immunogenic DNA complexes, thereby contributing to the initiation of wound repair in injured skin. After analyzing the structural properties of secreted neutrophil granule proteins, we identified OLFM4 as the only negatively charged molecule that interferes with NCP oligomerization. Through this interference, OLFM4 can inhibit neutrophil-mediated bacterial killing and DNA complex-dependent activation of Toll-like receptor 9 (TLR9) in plasmacytoid dendritic cells (pDCs) and neutrophils. While addition of exogenous OLFM4 blocks these processes, OLFM4 inhibition enhances neutrophil-dependent bacterial killing and DNA complex formation, ultimately leading to accelerated closure of skin wounds.
中性粒细胞阳离子蛋白（NCPs）是一组由活化的中性粒细胞释放的颗粒抗菌和炎症蛋白。这些蛋白质主要通过其正电荷结构发挥作用，促进与细菌膜的相互作用，并形成免疫原性 DNA 复合物，从而有助于受伤皮肤的伤口修复。在分析分泌性中性粒细胞颗粒蛋白的结构特性后，我们鉴定出 OLFM4 是唯一干扰 NCP 寡聚化的带负电荷分子。通过这种干扰，OLFM4 可以抑制中性粒细胞介导的细菌杀伤和浆细胞样树突状细胞（pDCs）和中性粒细胞中 Toll 样受体 9（TLR9）依赖于 DNA 复合物的激活。虽然添加外源性 OLFM4 会阻断这些过程，但 OLFM4 抑制会增强中性粒细胞依赖的细菌杀伤和 DNA 复合物形成，最终导致皮肤伤口更快愈合。
