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Serum amyloid A promotes LPS clearance and suppresses LPS ‐induced inflammation and tissue injury
Author(s) -
Cheng Ni,
Liang Yurong,
Du Xiaoping,
Ye Richard D
Publication year - 2018
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201745517
Subject(s) - serum amyloid a , inflammation , lipopolysaccharide , acute phase protein , immunology , sepsis , lipopolysaccharide binding protein , tumor necrosis factor alpha , innate immune system , genetically modified mouse , chemistry , transgene , biology , biochemistry , immune system , gene
Lipopolysaccharide ( LPS ) is a major microbial mediator for tissue injury and sepsis resulting from Gram‐negative bacterial infection. LPS is an external factor that induces robust expression of serum amyloid A ( SAA ), a major constituent of the acute‐phase proteins, but the relationship between SAA expression and LPS ‐induced tissue injury remains unclear. Here, we report that mice with inducible transgenic expression of human SAA 1 are partially protected against inflammatory response and lung injury caused by LPS and cecal ligation and puncture ( CLP ). In comparison, transgenic SAA 1 does not attenuate TNF α‐induced lung inflammation and injury. The SAA 1 expression level correlates inversely with the endotoxin concentrations in serum and lung tissues since SAA 1 binds directly to LPS to form a complex that promotes LPS uptake by macrophages. Disruption of the SAA 1‐ LPS interaction with a SAA 1‐derived peptide partially reduces the protective effect and exacerbates inflammation. These findings demonstrate that acute‐phase SAA provides innate feedback protection against LPS ‐induced inflammation and tissue injury.