Identification of procathepsin L (pCTS-L)-neutralizing monoclonal antibodies to treat potentially lethal sepsis.

ABSTRACT: Antibody-based strategies have been attempted to antagonize early cytokines of sepsis, but not yet been tried to target inducible late-acting mediators. Here, we report that the expression and secretion of procathepsin-L (pCTS-L) was induced by serum amyloid A (SAA) in innate immune cells, contributing to its late and systemic accumulation in experimental and clinical sepsis. Recombinant pCTS-L induced interleukin-6 (IL-6), IL-8, GRO-α/KC, GRO-β/MIP-2, and MCP-1 release in innate immune cells and moderately correlated with blood concentrations of these cytokines/chemokines in clinical sepsis. Mechanistically, pCTS-L interacted with Toll-like receptor 4 (TLR4) and the receptor for advanced glycation end products (RAGE) to induce cytokines/chemokines. Pharmacological suppression of pCTS-L wi

SUBMITTER: Zhu CS 

PROVIDER: S-EPMC9897667 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature