Erythrocytes restrict microvesicle‐induced production of reactive oxygen species by polymorphonuclear leukocytes

Abstract

Microvesicles (MVs) are extracellular vesicles released by several cell types upon activation or apoptosis. MVs have the potential to activate complement, which has been suggested to mediate their clearance. However, it is not clear how complement‐opsonized MVs are prevented from activating circulating polymorphonuclear leukocytes (PMNs) with release of reactive oxygen species (ROS) and potential damage of endothelium and other bystander cells as consequence. We hypothesized that binding of opsonized MVs to erythrocytes (Es) attenuates MV‐induced PMN activation. To test this, normal PMNs were exposed to MVs in the presence and absence of Es from allogenic healthy donors. As analyzed by flow cytometry, the presence of Es restricted the PMN binding of MVs by about 85% (p = 0.002) and mediated a 60–70% inhibition of the PMN production of the ROS H2O2, induced by MVs, when lipopolysaccharide was used as a primer (p = 0.002). The competitive binding of MVs to Es was partly dependent on complement, since EDTA inhibited MV binding to Es by 75%. These data suggest that Es, through competitive binding, may restrict MV‐induced activation of circulating PMNs and thereby serve a role as a regulator of PMN activation.

Binding of C1q to Galectin-3 Binding Protein on Microvesicles Released by Mononuclear Cells from Patients with Systemic Lupus Erythematosus

“…Furthermore, the SLE-related deficiencies of complement receptor type 1 (CR1) 30 may add to this picture. CR1 recognizes the opsonins C3b and C4b, which are likely deposited on MVs as a consequence of C1q-binding, and is vital for the removal of ICs and presumably also MVs from the circulation 30,31,32,33 32 .…”