Apolipoprotein Mimetic Peptide Inhibits Neutrophil-Driven Inflammatory Damage via Membrane Remodeling and Suppression of Cell Lysis.

ABSTRACT: Neutrophils are crucial for host defense but are notorious for causing sterile inflammatory damage. Activated neutrophils in inflamed tissue can liberate histone H4, which was recently shown to perpetuate inflammation by permeating membranes via the generation of negative Gaussian curvature (NGC), leading to lytic cell death. Here, we show that it is possible to build peptides or proteins that cancel NGC in membranes and thereby suppress pore formation, and demonstrate that they can inhibit H4 membrane remodeling and thereby reduce histone H4-driven lytic cell death and resultant inflammation. As a demonstration of principle, we use apolipoprotein A-I (apoA-I) mimetic peptide apoMP₁. X-ray structural studies and theoretical calculations show that apoMP₁ induces nanosc

SUBMITTER: Lee MW 

PROVIDER: S-EPMC8720511 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature