Bronchoalveolar Lavage Microvesicles Protect Burn-Injured Mice from Pulmonary Infection

Abstract

Background Pseudomonas aeruginosa (PA) is a major cause of morbidity and mortality among burn patients, despite antibiotic therapy. There is a need to identify innate immune defenses that prevent PA infection in injured adults in an effort to find therapeutic alternatives to antibiotics. Here, we tested our hypothesis that Microvesicles (MVs) in bronchoalveolar (BAL) fluid have a role in the immunity of the lung in response to pathogens. Study Design MVs were isolated from murine BAL fluid, quantified using nanoparticle tracking analysis, and injected into burn injured mice prior to PA infection. Survival was assessed and BAL bacterial loads enumerated. Neutrophil number and IL-6 activity were determined. Lungs were harvested and sphingosine (SPH) content analyzed via immunohistochemistry. Antimicrobial effects of MV and SPH enriched MVs were assessed in an in vitro assay. Results Burn injured mice have reduced BAL MV number and SPH content as compared to sham. When BAL MVs from healthy mice are administered to injured mice, survival and bacterial clearance are robustly improved. We further observed that intranasal administration of MVs restores SPH levels after burn injury, MVs directly kill bacteria, and this bacterial killing is increased when the MVs supplemented with SPH. Conclusion Using a pre-clinical model, BAL MVs are reduced after scald injury and BAL MV restoration to injured mice improves survival and bacterial clearance. The antimicrobial mechanisms leading to improved survival includes the quantity and SPH content of BAL MVs.

Neglected No More: Emerging Cellular Therapies in Traumatic Injury

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Mesenchymal stem cells‐derived extracellular vesicles in acute respiratory distress syndrome: a review of current literature and potential future treatment options

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miRNA-based therapeutic potential of stem cell-derived extracellular vesicles: a safe cell-free treatment to ameliorate radiation-induced brain injury

“…These relatively new strategies have been used successfully for a number of different conditions including stroke (Xin et al 2013), traumatic brain injury (Y. , and myocardial infarction (Timmers et al 2011;Barile et al 2014;Zhao et al 2015;Khan et al 2015). More specifically, intranasal administration of EV has been successful in treating Parkinson's Disease (Haney et al 2015), nasal allergies (Prado et al 2010), stroke (Kalani et al 2016), epilepsy-related brain damage (Long et al 2017), and lung injury (Rice et al 2017;Tan et al 2018). In addition, the previously mentioned EV-mediated delivery of miR-124 post-stroke utilized tail vein injections (Yang et al 2017).…”