Late Breaking Abstract - Myeloid-derived microvesicles as acute mediators of sepsis-induced lung vascular inflammation

Abstract

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 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.