45 Behavior and Effect of Nanoparticles on Neutrophil Recruitment in the Pulmonary Microcirculation

Abstract

Abstract NP exposure is frequently associated with adverse cardiovascular effects. A small fraction of NP deposited in lung has been shown to penetrate into the blood circulation. However, the interactions and effects of NP in the pulmonary microcirculation under healthy and pathophysiologic conditions such as LPS-induced acute lung injury are largely unknown. To visualize and quantify NP dynamics and pulmonary vascular innate immune responses elicited by different surface-modified NPs in real time, we applied state-of-the-art intra-vital microscopy in the alveolar region of murine lungs. I.v. injected polyethylene-glycol-amine (aPEG)-QDs and carboxyl-QDs exhibited a half-life time of 30 and 6 mins in the microcirculation and did not permanently interact with vessel wall. Blood flow velocity was significantly decreased after aPEG-QDs application in healthy mice, but did not further decrease the reduced microcirculatory perfusion after LPS treatment. In healthy mice, aPEG-QDs elicited a significant increase in neutrophil number in alveolar micro-vessels from 30 min upon application compared to controls, whereas cQDs induced only a slight neutrophil increment. Accordingly, the crawling velocity of neutrophils in pulmonary micro-vessels was significantly reduced after aPEG-QDs application. No effect of QDs on neutrophil number and crawling was detected in the LPS group. Importantly, neutrophil recruitment by aPEG-QDs was diminished by prior i.v. application of anti-TNFa, anti-E-selectin and anti-LFA-1 blocking antibodies. Taken together our data suggest that aPEG-QDs induced microvascular inflammation involving TNFa secretion, expression of the vascular cell adhesion molecule E-selectin and neutrophil integrin LFA-1, whereas QDs application did not alter LPS-dependent microvascular inflammation.