RT Journal Article SR Electronic T1 Late Breaking Abstract - Myeloid-derived microvesicles as acute mediators of sepsis-induced lung vascular inflammation JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 4468 DO 10.1183/13993003.congress-2020.4468 VO 56 IS suppl 64 A1 Diianeira Maria Tsiridou A1 Kieran Patrick O'Dea A1 Ying Ying Tan A1 Masao Takata YR 2020 UL http://erj.ersjournals.com/content/56/suppl_64/4468.abstract AB Background: Although circulating microvesicles (MVs), particularly myeloid (M-MVs) and platelet-derived (P-MVs) are elevated in sepsis, little is known of their contribution to acute lung injury (ALI). Recently, we showed that M-MVs, but not P-MVs, from endotoxaemic mice induced pulmonary vascular injury in a mouse isolated-perfused lung model. Here, we used an in vitro human cell culture model of lung microvascular inflammation to explore the clinical significance of these observations.Methods: Heparinised whole blood from healthy donors was treated with lipopolysaccharide (100ng/ml) for 3h, and M-MVs (CD11b+) and P-MVs (CD61+) obtained by positive immunomagnetic-bead separation. MVs were incubated with human lung microvascular endothelial cells (HLMEC) in monoculture or in co-culture with peripheral blood mononuclear cells (PBMC) for 4h. Responses were quantified by flow cytometry and ELISA.Results: In HLMEC-PBMC co-culture, M-MVs increased cell adhesion molecule expression on HLMEC (ICAM-1 p<0.0001; VCAM-1 p<0.0001; E selectin p<0.0001) and release of pro-inflammatory cytokines (IL-8 p<0.0001; TNFα p<0.0001; MCP-1 p<0.05) compared to untreated controls. By contrast, only VCAM-1 was upregulated by P-MVs (p<0.05). Neither MV subtype produced any effect in HLMEC monoculture.Conclusion: Using a novel whole-blood assay for MV production and subtype isolation, our findings suggest that M-MVs released during endotoxaemia are potent mediators of lung microvascular inflammation and that PBMC are critical for this response. M-MVs may, therefore, serve as vehicles for systemic propagation of inflammation, inducing end-organ injury and having a key role in the pathogenesis of indirect sepsis-induced ALI.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 4468.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).