High-molecular-weight kininogen is a critical component of host defense against <i>Escherichia coli</i> sepsis.

ABSTRACT: High-molecular-weight kininogen (HK) is known to bind lipopolysaccharides (LPS) with high affinity and serves as a crucial LPS carrier in circulation, supporting endotoxemia. However, its role in host defense against Gram-negative bacterial infection remains unclear. Here we demonstrate that HK directly binds to Escherichia coli (E. coli) via LPS and rapidly localizes to sites of infection. HK-deficient mice (Kng1^-/-) showed increased susceptibility to infection, with increased bacterial dissemination, lung injury, and proinflammatory cytokine production. In contrast, endogenous expression of human HK in Kng1^-/- mice restored survival, limited bacterial spread, and reduced tissue damage. Mechanistically,

SUBMITTER: Yang A 

PROVIDER: S-EPMC12708997 | biostudies-literature | 2025 Jan-Dec

REPOSITORIES: biostudies-literature