AI Article Synopsis
- - Neutrophil cationic proteins (NCPs) are antimicrobial and inflammatory proteins released by activated neutrophils that help in fighting bacteria and promoting wound healing through their positive charge.
- - OLFM4 is a unique negatively charged protein that disrupts the formation of NCP complexes, which in turn inhibits the neutrophils' ability to kill bacteria and activate certain immune responses.
- - Blocking OLFM4 enhances the effectiveness of neutrophils in combating bacteria and aids in faster skin wound closure, highlighting its role in modulating immune responses during healing.
Article Abstract
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.
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| http://dx.doi.org/10.1016/j.celrep.2024.114863 | DOI Listing |
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