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Extracellular CIRP and TREM‐1 axis promotes ICAM‐1‐Rho‐mediated NETosis in sepsis
Author(s) -
Murao Atsushi,
Arif Adnan,
Brenner Max,
Denning NaomiLiza,
Jin Hui,
Takizawa Satoshi,
Nicastro Benjamin,
Wang Ping,
Aziz Monowar
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202000482r
Subject(s) - neutrophil extracellular traps , extracellular , icam 1 , intercellular adhesion molecule 1 , intracellular , chemistry , receptor , inflammation , microbiology and biotechnology , sepsis , biology , immunology , biochemistry
Extracellular cold‐inducible RNA‐binding protein (eCIRP) is a damage‐associated molecular pattern (DAMP). Intercellular adhesion molecule‐1 (ICAM‐1) expressing neutrophils produce excessive amounts of neutrophil extracellular traps (NETs). We reveal that eCIRP generates ICAM‐1 + neutrophils through triggering receptor expressed on myeloid cells‐1 (TREM‐1) and the ICAM‐1 + neutrophils involve Rho GTPase to promote NETosis. Treatment of BMDN with rmCIRP increased the frequency of ICAM‐1 + BMDN, while rmCIRP‐treated TREM‐1 −/− BMDN or pretreatment of BMDN with TREM‐1 inhibitor LP17 significantly decreased the frequency of ICAM‐1 + neutrophils. The frequencies of ICAM‐1 + neutrophils in blood and lungs were markedly decreased in rmCIRP‐injected mice or septic mice treated with LP17. Coculture of ICAM‐1 −/− neutrophils or wild‐type (WT) neutrophils with WT macrophages in the presence of a peptidylarginine deiminase 4 (PAD4) inhibitor reduced TNF‐α and IL‐6 compared to WT neutrophils treated with rmCIRP. Treatment of ICAM‐1 −/− neutrophils with rmCIRP resulted in reduced quantities of NETs compared to WT rmCIRP‐treated neutrophils. Treatment of BMDN with rmCIRP‐induced Rho activation, while blockade of ICAM‐1 significantly decreased Rho activation. Inhibition of Rho significantly decreased rmCIRP‐induced NET formation in BMDN. TREM‐1 plays a critical role in the eCIRP‐mediated increase of ICAM‐1 expression in neutrophils, leading to the increased NET formation via Rho activation to exaggerate inflammation.