Premium
Inhibition of platelet‐induced NETosis via disruption of CXCL4/CCL5‐heteromerformation ameliorates organ damage after in ventilator‐induced lung injury (146.3)
Author(s) -
Herter Jan,
Rossaint Jan,
Soehnlein Oliver,
Weber Christian,
Stadtmann Anika,
Block Helena,
Aken Hugo,
Zarbock Alexander
Publication year - 2014
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/fasebj.28.1_supplement.146.3
Subject(s) - platelet , neutrophil extracellular traps , chemistry , inflammation , ccl5 , microbiology and biotechnology , pathogenesis , platelet activation , immunology , pharmacology , cancer research , biochemistry , biology , cytotoxic t cell , in vitro , il 2 receptor
Platelet leukocyte interactions are a hallmark of inflammation. We here report that platelet induced formation of neutrophils extracellular traps (NETs) is crucial for neutrophil recruitment following ventilator induced lung injury (VILI) as the inhibition of NET formation by DNAse dampens the severity of VILI. Furthermore, administration of MKEY, a peptide reported to disrupt heterodimer formation of platelet derived CXCL4 and CCL5, or blocking antibodies against CXCL4 and/or CCL5 caused a decrease in neutrophil influx and organ damage that was comparable to DNAase treatment or platelet depletion. The combination of platelet‐depletion and MKEY or antibodies against CXCL4/CCL5 did not show additive effects. Taken together, our data indicates that platelet derived CXCL5/CCL5 heterodimer formation is critical for platelet induced NET‐formation contributes crucially to the pathogenesis of VILI. Grant Funding Source : Supported by DFG: AZ428/3‐1, AZ428/6‐1, SFB1009/A5 to AZ, HE6810/1‐1 to JH, IZKF: SEED01/12 to JR