Premium
Procoagulant and proinflammatory effects of red blood cells on lipopolysaccharide‐stimulated monocytes
Author(s) -
Østerud B.,
Unruh D.,
Olsen J. O.,
Kirchhofer D.,
Owens A. P.,
Bogdanov V. Y.
Publication year - 2015
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.13041
Subject(s) - proinflammatory cytokine , lipopolysaccharide , chemokine , platelet , monocyte , tissue factor , chemistry , immunology , antigen , microbiology and biotechnology , whole blood , inflammation , biology , medicine , coagulation
Summary Background We aimed to evaluate the mechanisms underlying the effects of red blood cells ( RBC s) on the reactivity of monocytes to lipopolysaccharide ( LPS ) stimulation. Methods Measurements of tissue factor ( TF ) antigen and activity were performed on freshly isolated white blood cells ( WBCs )/platelets resuspended in heparinized plasma, as well as cultured monocytic cells. Results In a dose‐dependent manner, RBC s significantly enhanced LPS ‐induced TF activity and antigen levels in blood monocytes; potentiation of TF activity by both human and murine RBC s did not require the presence of neutrophils and/or platelets. We also measured the levels of monocyte chemotactic protein‐1 (MCP‐1), the key proinflammatory chemokine that binds to duffy antigen receptor for chemokines (DARC) on RBC surface, in plasma and RBC lysates after the incubation of RBC s with WBC /platelets; at the concentrations corresponding to normal blood counts, RBC s exerted a significant influence on the free plasma levels of MCP‐1, with about two‐thirds of detectable MCP‐1 post‐ LPS stimulation being associated with RBC s. Critically, DARC‐deficient murine RBC s failed to enhance LPS ‐induced TF activity, confirming the mechanistic significance of RBC ‐ DARC . Conclusions Our study reports a novel mechanism by which RBC s promote procoagulant and proinflammatory sequelae of WBC exposure to LPS , likely mediated by RBC ‐ DARC in the microenvironment(s) that bring monocytes and RBC s in close proximity.