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.
Highlights
The phospholipase A2 (PLA2) superfamily of enzymes catalyze the hydrolysis of ester bonds at the sn-2 position of glycerophospholipids generating lysophospholipids and free fatty acids.Their physiological roles range from phospholipid biosynthesis/membrane remodeling, where mainly cytosolic types are involved [1], to cell signaling, host defense [2], and to the generation of potent inflammatory mediators, such as eicosanoids and platelet activating factor (PAF) [3]
We showed that total PLA2 activity levels were elevated in Bronchoalveolar lavage (BAL) fluid from early acute respiratory distress syndrome (ARDS) patients and that this increase was mainly due to secretory PLA2 isoforms [13,15]
We found that: (1) BAL fluids from all the groups of patients with early and late ARDS and controls contained EVs bearing biochemical (e.g., CD63 protein marker) and morphological characteristics of exosomes, (2) PLA2G2A mRNA was present in all the EV preparations but most abundantly in early ARDS EVs, and, (3) sPLA2-IIA protein was detected in the small EV preparations only from patients with early ARDS
Summary
The phospholipase A2 (PLA2) superfamily of enzymes catalyze the hydrolysis of ester bonds at the sn-2 position of glycerophospholipids generating lysophospholipids and free fatty acids Their physiological roles range from phospholipid biosynthesis/membrane remodeling, where mainly cytosolic types are involved [1], to cell signaling, host defense [2], and to the generation of potent inflammatory mediators, such as eicosanoids and platelet activating factor (PAF) [3]. In the case of inflammation, especially during the acute phase of ARDS, inflammatory cells, including blood monocytes and polymorphonuclear cells, invade from the circulation into the lung, along with various pro-inflammatory and anti-inflammatory agents due to the increased alveolar-capillary permeability [18] The composition of these cell populations, their activation state, the type of secreted substances and the patient’s outcome depend largely on the type of insult and the time elapsed from the insult [19,20,21,22]. BAL fluid contains lung surfactant formations, namely, the surface-active phospholipid/protein material that lines the alveoli
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