Original Article
Procoagulant and proinflammatory effects of red blood cells on lipopolysaccharide‐stimulated monocytes

https://doi.org/10.1111/jth.13041Get rights and content
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Summary

Background

We aimed to evaluate the mechanisms underlying the effects of red blood cells (RBCs) 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, RBCs significantly enhanced LPS‐induced TF activity and antigen levels in blood monocytes; potentiation of TF activity by both human and murine RBCs 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 RBCs with WBC/platelets; at the concentrations corresponding to normal blood counts, RBCs 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 RBCs. Critically, DARC‐deficient murine RBCs failed to enhance LPS‐induced TF activity, confirming the mechanistic significance of RBC‐DARC.

Conclusions

Our study reports a novel mechanism by which RBCs promote procoagulant and proinflammatory sequelae of WBC exposure to LPS, likely mediated by RBC‐DARC in the microenvironment(s) that bring monocytes and RBCs in close proximity.

Keywords

blood coagulation
chemokines
erythrocytes
lipopolysaccharides
thromboplastin

Cited by (0)

Manuscript handled by: W. Ruf

Final decision: P. H. Reitsma, 12 June 2015