Platelets promote macrophage polarisation towards pro-inflammatory phenotype and increase survival of septic mice

AGOSTINA CARESTIA; HEBE AGUSTINA MENA; CINTHIA M OLEXEN; JUAN M. ORTIZ WILCZYÑSK; SOLEDAD NEGROTTO; ANDREA E ERRASTI; RICARDO M GOMEZ; CRAIG N JENNE; EUGENIO ANTONIO CARRERA SILVA; MIRTA SCHATTNER

Cell Reports

CELL PRESS

Año: 2019

2211-1247

We investigated the contribution of human platelets to macrophage effector properties inthe presence of lipopolysaccharide (LPS) as well as the beneficial effects and time framefor platelet transfusion in septic animals. Our results show that platelets sequester bothpro-(TNF-a/IL-6) and anti-(IL-10) inflammatory cytokines released by monocytes. Low LPSconcentrations (0.01 ng/ml) induced M2 macrophage polarisation by decreasing CD64 andaugmenting CD206 and CD163 expression; yet the presence of platelets skewedmonocytes towards M1 phenotype in a cell contact-dependent manner via the GPIb-CD11b axis. Accordingly, platelet-licensed macrophages showed increased TNF-a levels,bacterial phagocytic activity and a reduced healing capability. Platelet transfusionincreased iNOS+ macrophages, improving bacterial clearance and survival rates in septicmice up to 6 h post-infection, an effect that was abolished by CD11b and GPIb blockade.Our results demonstrate that platelets orchestrate macrophage effector responsesimproving the clinical outcome of sepsis in a narrow but relevant time frame.