Erythrocyte microparticles can induce kidney vaso-occlusions in a murine model of sickle cell disease
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Updated: May 18, 2026
Endothelialized Microfluidics for Studying Microvascular Interactions in Hematologic Diseases
Published on: June 22, 2012
Stéphane M Camus1, Blandine Gausserès, Philippe Bonnin
1Paris Center for Cardiovascular Research, INSERM UMR s-970, Hôpital Européen Georges Pompidou, et Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Abstract:
Patients with sickle cell disease suffer from painful crises associated with disseminated vaso-occlusions, increased circulating erythrocyte microparticles (MPs), and thrombospondin-1 (TSP1). MPs are submicron membrane vesicles shed by compromised or activated cells. We hypothesized that TSP1 mediates MP shedding and participates in vaso-occlusions. We injected TSP1 to transgenic SAD mice with sickle cell disease and characterized circulating phosphatidylserine+ MPs by FACS. TSP1 stimulated MPs in plasma and initiated vaso-occlusions within minutes. In vitro, TSP1 triggered rapid erythrocyte conversion into spicule-covered echinocytes, followed by MP shedding. MP shedding was recapitulated by peptides derived from the TSP1 carboxyterminus. We purified MPs shed by erythrocytes in vitro and administered them back to SAD mice. MPs triggered immediate renal vaso-occlusions. In vitro, MPs triggered the production of radical oxygen species by endothelial monolayers, favored erythrocyte adhesion, and induced endothelial apoptosis. MPs also compromised vasodilation in perfused microvessels. These effects were inhibited by saturating MP phosphatidylserine with annexin-V, or with inhibitors of endothelial ROS production. We conclude that TSP1 triggers erythrocyte MP shedding. These MPs induce endothelial injury and facilitate acute vaso-occlusive events in transgenic SAD mice. This work supports a novel concept that toxic erythrocyte MPs may connect sickle cell anemia to vascular disease.
Insights
Thrombospondin-1 (TSP1) triggers red blood cell shedding of microparticles (MPs) in sickle cell disease models. These toxic MPs cause blood vessel damage and vaso-occlusion, linking sickle cell anemia to vascular disease.
Area of Science:
- Hematology
- Vascular Biology
- Cell Biology
Background:
- Sickle cell disease (SCD) is characterized by painful vaso-occlusive crises.
- Increased circulating erythrocyte microparticles (MPs) and thrombospondin-1 (TSP1) are observed in SCD patients.
- The role of TSP1 in MP shedding and vaso-occlusion in SCD is not fully understood.
Purpose of the Study:
- To investigate the role of TSP1 in mediating erythrocyte microparticle shedding.
- To determine if TSP1-induced MPs contribute to vaso-occlusion in a sickle cell disease mouse model.
- To elucidate the mechanisms by which MPs induce vascular injury.
Main Methods:
- TSP1 was administered to transgenic SAD mice with sickle cell disease.
- Circulating phosphatidylserine-positive MPs were quantified using flow cytometry (FACS).
- In vitro studies examined erythrocyte morphology changes, MP shedding induced by TSP1 and its peptides, and endothelial cell responses to MPs.
Main Results:
- TSP1 administration rapidly increased circulating MPs and induced vaso-occlusions in SAD mice.
- In vitro, TSP1 induced erythrocyte transformation into echinocytes followed by MP shedding.
- Administered MPs caused renal vaso-occlusions, increased endothelial reactive oxygen species (ROS) production, promoted erythrocyte adhesion, induced endothelial apoptosis, and impaired vasodilation.
Conclusions:
- TSP1 is a key trigger for erythrocyte microparticle shedding in sickle cell disease.
- Erythrocyte-derived MPs contribute significantly to endothelial injury and acute vaso-occlusive events.
- This study proposes a novel mechanism linking sickle cell anemia to vascular complications via toxic erythrocyte MPs.
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