The exposure to environmental particulate matter induces acute inflammatory leukocyte recruitment by boosting endothelial and myeloid cell activation and the release of pro-inflammatory cytokines

MARCHINI, TIMOTEO; MICHEL, NATALY; TASAT, DEBORAH; WOLF, DENNIS; BODE, CHRISTOPH; EVELSON, PABLO; ZIRLIK, ANDREAS

Ferrara

Conferencia; Cellular Environmental Stressors in Biology and Medicine: Focus on Redox Reactions; 2014

Universita di Ferrara

The exposure to environmental particulate matter (PM) is associated with increased morbidity and mortality rates due to cardiovascular diseases. In this scenario, systemic inflammation has been suggested to play a predominant role, even though little is known about the underling mechanism. Therefore, the aim of this study was to clarify the mechanism of PM-induced inflammation in an in vivo animal model of acute exposure to PM. Wild type C57BL/6 mice were intranasally instilled with Residual Oil Fly Ashes (ROFA) (1 mg/kg body weight). After 3 h, leukocyte trafficking was imaged by intravital microscopy on mesenteric venules. Plasma cytokine profile, endothelial cells (EC) and leukocyte subtypes activation were evaluated by flow cytometry. Leukocyte rolling and adhesion was significantly increased in mice exposed to ROFA. In this group, up-regulation of several adhesion molecules was observed (I-CAM and V-CAM in EC, and activated CD11b in myeloid cells), together with increased TNFα, IL-6 and MCP-1 plasma levels. In vitro experiments confirmed that pro-inflammatory cytokines present in plasma from ROFA-exposed mice potentiate EC and leukocyte activation, while a direct effect of ROFA particles was observed in monocytes and macrophages, but not in neutrophils and EC. Interestingly, depletion of macrophages, but not of lymphocytes limited ROFA-mediated inflammatory response in vivo. The present findings indicate that an acute exposure to environmental PM induces macrophage activation, which, in turn, might drive systemic inflammation leading to PM-associated adverse cardiovascular effects.