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Erythrocyte-derived ectosomes have immunosuppressive properties
Salima Sadallah1, Ceylan Eken, Jürg A Schifferli
1Department of Biomedicine, University Hospital Basel, Basel, Switzerland. salima.sadallah@unibas.ch
Abstract:
Several clinical studies have suggested that blood transfusions are immunosuppressive. Whereas there have been reports describing immunosuppression induced by leukocytes or fragments thereof, the possibility that microparticles, released by erythrocytes during storage, are also involved was not investigated. We present evidence here that such microparticles have all the properties of ectosomes including size, the presence of a lipid membrane, and the specific sorting of proteins. These erythrocyte-derived ectosomes (E-ecto) fixed C1q, which was followed by activation of the classical pathway of complement with binding of C3 fragments. Similarly to ectosomes released by PMN, they express phosphatidylserine on their surface membrane, suggesting that they may react with and down-regulate cells of the immune system. In vitro, they were taken up by macrophages, and they significantly inhibited the activation of these macrophages by zymosan A and LPS, as shown by a significant drop in TNF-alpha and IL-8 release (respectively, 80% and 76% inhibitions). In addition, the effect of E-ecto was not transient but lasted for at least 24 h. In sum, E-ecto may interfere with the innate immune system/inflammatory reaction. Therefore, E-ecto transfused with erythrocytes may account for some of the immunosuppressive properties attributed to blood transfusions.
Insights
Erythrocyte-derived microparticles (E-ecto) from stored blood exhibit immunosuppressive properties. These microparticles inhibit macrophage activation, potentially explaining the immunosuppressive effects of blood transfusions.
Area of Science:
- Immunology
- Hematology
- Cell Biology
Background:
- Clinical studies indicate blood transfusions possess immunosuppressive qualities.
- While leukocyte-derived factors are known contributors, erythrocyte-derived microparticles' role remains unexplored.
Purpose of the Study:
- To investigate the potential immunosuppressive role of microparticles released by erythrocytes during blood storage.
- To characterize these erythrocyte-derived ectosomes (E-ecto) and their interaction with the immune system.
Main Methods:
- Characterization of E-ecto for ectosome properties (size, lipid membrane, protein sorting).
- Assessed complement activation (C1q, C3 fixation) and phosphatidylserine expression on E-ecto.
- In vitro studies involving macrophage uptake of E-ecto and measurement of inflammatory cytokine release (TNF-alpha, IL-8) upon stimulation.
Main Results:
- E-ecto demonstrated characteristics of ectosomes and initiated complement activation.
- E-ecto expressed phosphatidylserine, suggesting immune regulatory potential.
- Macrophages incubated with E-ecto showed significantly inhibited activation by zymosan A and LPS, with 80% and 76% reduction in TNF-alpha and IL-8, respectively.
- This inhibitory effect was sustained for at least 24 hours.
Conclusions:
- Erythrocyte-derived ectosomes (E-ecto) possess immunosuppressive properties by interfering with innate immune responses.
- E-ecto may contribute to the observed immunosuppression associated with blood transfusions.
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