Secretory Phospholipase A2-IIA Protein and mRNA Pools in Extracellular Vesicles of Bronchoalveolar Lavage Fluid from Patients with Early Acute Respiratory Distress Syndrome: A New Perception in the Dissemination of Inflammation?

Stylianos Papadopoulos; Eleftheria Kazepidou; Marianna H Antonelou; George Leondaritis; Alexia Tsapinou; Vasilios P Koulouras; Apostolos Avgeropoulos; George Nakos; Marilena E Lekka

doi:10.3390/ph13110415

Secretory Phospholipase A₂-IIA Protein and mRNA Pools in Extracellular Vesicles of Bronchoalveolar Lavage Fluid from Patients with Early Acute Respiratory Distress Syndrome: A New Perception in the Dissemination of Inflammation?

Pharmaceuticals (Basel). 2020 Nov 23;13(11):415. doi: 10.3390/ph13110415.

Authors

Stylianos Papadopoulos¹, Eleftheria Kazepidou¹, Marianna H Antonelou², George Leondaritis³, Alexia Tsapinou¹, Vasilios P Koulouras⁴, Apostolos Avgeropoulos⁵, George Nakos⁴, Marilena E Lekka¹

Affiliations

¹ Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 451 10 Ioannina, Greece.
² Section of Cell Biology & Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens (NKUA), Panepistimioupolis, 15784 Athens, Greece.
³ Laboratory of Pharmacology, School of Medicine, University of Ioannina, 451 10 Ioannina, Greece.
⁴ Department of Intensive Care Medicine, School of Medicine, University of Ioannina, 451 10 Ioannina, Greece.
⁵ Department of Materials Science, University of Ioannina, 451 10 Ioannina, Greece.

Abstract

Secretory phospholipase-IIA A₂ (sPLA₂-IIA) is expressed in a variety of cell types under inflammatory conditions. Its presence in the bronchoalveolar lavage (BAL) fluid of patients with acute respiratory distress syndrome (ARDS) is associated with the severity of the injury. Exosomal type extracellular vesicles, (EVs), are recognized to perform intercellular communication. They may alter the immune status of recipient target cells through cargo shuttling. In this work, we characterized the exosomal type EVs isolated from BAL fluid of patients with early and late ARDS as compared to control/non-ARDS patients, through morphological (confocal and electron microscopy) and biochemical (dynamic light scattering, qRT-PCR, immunoblotting) approaches. We provide evidence for the presence of an sPLA₂-IIA-carrying EV pool that coprecipitates with exosomes in the BAL fluid of patients with ARDS. PLA2G2A mRNA was present in all the samples, although more prominently expressed in early ARDS. However, the protein was found only in EVs from early phase ARDS. Under both forms, sPLA₂-IIA might be involved in inflammatory responses of recipient lung cells during ARDS. The perception of the association of sPLA₂-IIA to the early diagnosis of ARDS or even with a mechanism of development and propagation of lung inflammation can help in the adoption of appropriate and innovative therapeutic strategies.

Keywords: acute lung injury; acute respiratory distress syndrome; bronchoalveolar lavage fluid; exosomes; extracellular vesicles; immuno-TEM; phospholipase A2.