title: Procoagulant and proinflammatory effects of red blood cells on lipopolysaccharide-stimulated monocytes.
abstract: 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.
authors.affiliation: K.G. Jebsen TREC, IMB, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: B
authors.initials: B
authors.lastname: Østerud
authors.affiliation: Division of Hematology/Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: D
authors.initials: D
authors.lastname: Unruh
authors.affiliation: Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
authors.forename: J O
authors.initials: JO
authors.lastname: Olsen
authors.affiliation: Early Discovery Biochemistry, Genentech, Inc, San Francisco, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Kirchhofer
authors.affiliation: Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Owens
authors.affiliation: Division of Hematology/Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: V Y
authors.initials: VY
authors.lastname: Bogdanov
mesh_terms: D000328:Adult; D000818:Animals; D006801:Humans; D051379:Mice; D001777:Blood Coagulation / Q000502:physiology; D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D004375:Duffy Blood-Group System / Q000097:blood / Q000276:immunology; D019446:Endotoxemia / Q000097:blood / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D005786:Gene Expression Regulation; D007249:Inflammation / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology / Q000633:toxicity; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000097:blood / Q000172:deficiency / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood; D013925:Thromboplastin / Q000096:biosynthesis / Q000235:genetics
chemical_list: C473745:ACKR1 protein, human; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D004375:Duffy Blood-Group System; C433788:lipopolysaccharide, E. coli O26-B6; C440499:lipopolysaccharide, Escherichia coli O111 B4; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D012333:RNA, Messenger; D013925:Thromboplastin; C483025:Ackr1 protein mouse
keywords: blood coagulation; chemokines; erythrocytes; lipopolysaccharides; thromboplastin