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Monocyte‐mediated activation of endothelial cells occurs only after binding to extracellular vesicles from red blood cell products, a process mediated by β‐integrin
Author(s) -
Straat Marleen,
van Hezel Maike E.,
Böing Anita,
TuipDe Boer Anita,
Weber Nina,
Nieuwland Rienk,
van Bruggen Robin,
Juffermans Nicole P.
Publication year - 2016
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.13851
Subject(s) - flow cytometry , monocyte , microbiology and biotechnology , umbilical vein , biology , von willebrand factor , endothelial stem cell , cell adhesion molecule , inflammation , cell adhesion , immunology , proinflammatory cytokine , cd14 , endothelium , tissue factor , cell , platelet , coagulation , medicine , in vitro , biochemistry , psychiatry , endocrinology
BACKGROUND Red blood cell (RBC) transfusion is associated with organ failure. The mechanism remains unknown, but may include adherence of blood cells to the microvasculature. We hypothesized that RBC‐derived extracellular vesicles (EVs) interact with monocytes to activate endothelial cells. STUDY DESIGN AND METHODS Human umbilical vein endothelial cells were incubated with supernatant from fresh and stored RBC units either containing EVs or depleted from EVs, with or without the addition of immune cells. We measured expression of adhesion markers by flow cytometry and markers of coagulation and inflammation in the culture medium. We studied phagocytosis of EVs by monocytes by using confocal microscopy and flow cytometry. RESULTS Incubation of endothelial cells with monocytes alone did not induce up regulation of adhesion markers. The addition of both monocytes and supernatant from RBCs containing EVs resulted in up regulation of endothelial expression of intercellular adhesion molecule 1 and E‐selectin when compared to baseline. Up regulation was absent when stimulated with RBC supernatant depleted from EVs. EVs are phagocytosed by monocytes, which was partly abrogated after coincubation with two different complement receptor 3 (CR3)‐blocking antibodies. Addition of RBC‐derived EVs also increased levels of von Willebrand factor (VWF). There were no differences between groups related to storage time. CONCLUSION EVs from RBC transfusion bags activate monocytes with subsequent up regulation of endothelial cell adhesion markers. EVs are phagocytosed by monocytes through CR3. Furthermore, these EVs proved to be a source of VWF. These effects are unrelated to storage time. Thereby, EVs from RBC transfusion bags induce a proinflammatory and procoagulant endothelial cell response.