Abstract/Description
Background: Extracellular vesicles (EVs) are small lipid-bound particles containing proteins and RNAs, whose role in intercellular communication and signaling is critical for homeostasis or inflammatory responses. Patients with acute lung injury display changes in EVs number, cargo content and signature compared to healthy individuals.
Hypothesis: We have hypothesized that EVs may play a role in the pathogenesis of acute lung, by transferring harmful mediators of inflammation and disrupting recipient cells homeostasis.
Methods: C57BL/6j mice (8-10 weeks old, 25g BW) were intratracheally instilled with 50µL of 5*1010- 11 EVs isolated from Human Lung Microvascular Endothelial cells (HLMVEC) exposed to 1 µg LPS. Mice were monitored clinically for weight, S/F ratio and signs of distress. After 72 hours, parameters of lung function were measured via Flexivent (SICREQ), bronchoalveolar lavage fluid (BALF) collected and lungs harvested for molecular and histological analysis.
Results: Mice instilled with inflammatory-derived EVs display progressive weight loss, and a reduction in the S/F ratio 24 hours after EVs exposure. EVs dose dependently provoked histological signs of acute lung injury via H&E staining. Analysis of BALF indicated an increased cellularity for both EVs concentrations of neutrophils. Only the highest dose provoked a significant reduction in pressure volume relationships measured via Flexivent.
Conclusion: During inflammatory conditions, endothelial cells produce EVs that have a pathogenic potential toward the alveolar structures. These preliminary reports may open avenues for novel therapeutic measures targeting EVs release or internalization. The EVs-effects on the lung structures observed here, may similarly be involved in the pathogenesis of acute distress respiratory syndrome (ARDS) observed in indirect sepsis.
Faculty Advisor/Mentor Department
Frank Reidy Research Center for Bioelectrics
College/School/Affiliation
College of Sciences
Included in
Amino Acids, Peptides, and Proteins Commons, Lipids Commons, Pulmonology Commons, Respiratory System Commons, Wounds and Injuries Commons
Investigating Extracellualr Vesicles Role in the Pathogenesis of Acute Lung Injury
Background: Extracellular vesicles (EVs) are small lipid-bound particles containing proteins and RNAs, whose role in intercellular communication and signaling is critical for homeostasis or inflammatory responses. Patients with acute lung injury display changes in EVs number, cargo content and signature compared to healthy individuals.
Hypothesis: We have hypothesized that EVs may play a role in the pathogenesis of acute lung, by transferring harmful mediators of inflammation and disrupting recipient cells homeostasis.
Methods: C57BL/6j mice (8-10 weeks old, 25g BW) were intratracheally instilled with 50µL of 5*1010- 11 EVs isolated from Human Lung Microvascular Endothelial cells (HLMVEC) exposed to 1 µg LPS. Mice were monitored clinically for weight, S/F ratio and signs of distress. After 72 hours, parameters of lung function were measured via Flexivent (SICREQ), bronchoalveolar lavage fluid (BALF) collected and lungs harvested for molecular and histological analysis.
Results: Mice instilled with inflammatory-derived EVs display progressive weight loss, and a reduction in the S/F ratio 24 hours after EVs exposure. EVs dose dependently provoked histological signs of acute lung injury via H&E staining. Analysis of BALF indicated an increased cellularity for both EVs concentrations of neutrophils. Only the highest dose provoked a significant reduction in pressure volume relationships measured via Flexivent.
Conclusion: During inflammatory conditions, endothelial cells produce EVs that have a pathogenic potential toward the alveolar structures. These preliminary reports may open avenues for novel therapeutic measures targeting EVs release or internalization. The EVs-effects on the lung structures observed here, may similarly be involved in the pathogenesis of acute distress respiratory syndrome (ARDS) observed in indirect sepsis.