Selective protein aggregation confines and inhibits endotoxins in wounds: Linking host defense to amyloid formation

Jitka Petrlova; Erik Hartman; Ganna Petruk; Jeremy Chun Hwee Lim; Sunil Shankar Adav; Sven Kjellström; Manoj Puthia; Artur Schmidtchen

doi:10.1016/j.isci.2023.107951

Selective protein aggregation confines and inhibits endotoxins in wounds: Linking host defense to amyloid formation

iScience. 2023 Sep 19;26(10):107951. doi: 10.1016/j.isci.2023.107951. eCollection 2023 Oct 20.

Authors

Jitka Petrlova¹, Erik Hartman¹, Ganna Petruk¹, Jeremy Chun Hwee Lim¹, Sunil Shankar Adav², Sven Kjellström³, Manoj Puthia¹, Artur Schmidtchen^{1

4}

Affiliations

¹ Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, 22184 Lund, Sweden.
² School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore.
³ Department of Clinical Sciences, BioMS, Lund University, Lund, Sweden.
⁴ Dermatology, Skane University Hospital, 22185 Lund, Sweden.

Abstract

Bacterial lipopolysaccharide (LPS) induces rapid protein aggregation in human wound fluid. We aimed to characterize these LPS-induced aggregates and their functional implications using a combination of mass spectrometry analyses, biochemical assays, biological imaging, cell experiments, and animal models. The wound-fluid aggregates encompass diverse protein classes, including sequences from coagulation factors, annexins, histones, antimicrobial proteins/peptides, and apolipoproteins. We identified proteins and peptides with a high aggregation propensity and verified selected components through Western blot analysis. Thioflavin T and Amytracker staining revealed amyloid-like aggregates formed after exposure to LPS in vitro in human wound fluid and in vivo in porcine wound models. Using NF-κB-reporter mice and IVIS bioimaging, we demonstrate that such wound-fluid LPS aggregates induce a significant reduction in local inflammation compared with LPS in plasma. The results show that protein/peptide aggregation is a mechanism for confining LPS and reducing inflammation, further emphasizing the connection between host defense and amyloidogenesis.

Keywords: Bacteriology; Immunology; cell biology.