Microvesicles in bronchoalveolar lavage as a potential biomarker of COPD.

Erica Bazzan,Marina Saetta,Davide Biondini,Alessandro Celi,Tommaso Neri,Manuel G Cosio,Elisabetta Balestro,Claudia Maria Radu,Paolo Simioni,Alvise Casara,Mariaenrica Tinè,Umberto Semenzato

doi:10.1152/ajplung.00362.2020

Abstract

Microvesicles (MVs) released from almost all cells are recognized as cell communication tools. MVs have been investigated in several inflammatory diseases but poorly in biological fluids like bronchoalveolar lavage (BAL) of smokers. The purpose of this study was to investigate the presence and source of MVs in BAL of smokers with and without chronic obstructive pulmonary disease (COPD) compared with nonsmoking controls. Using flow cytometry in BAL, we detected endothelial and alveolar macrophage (AM)-derived MVs and found a higher number of AM-MVs in the BAL of smokers with COPD than in smokers without COPD and nonsmokers, which correlated with the pack-years (r = 0.46; P = 0.05) and with the degree of airway obstruction measured by the forced expiratory volume in 1 s percent predicted (r = -0.56; P = 0.01). Endothelial and alveolar macrophage-derived MVs are present and measurable in human BAL fluid. In response to smoking and to the development of COPD, inflammatory signals in AM-derived MVs can be quantified, and their numbers are related to the pack-years and the decrease in lung function. These results open the opportunity for future investigation of these microvesicles as biomarkers and possible mechanistic guides in COPD.

Highlights

Cell-to-cell communication is an essential component for mammalian development and preservation of homeostasis and for efficient responses to threats within the surrounding environment
We found that MVs expressing CD14, a key molecule in the activation of innate immune cells expressed on cells of the myelomonocyte lineage including monocytes, macrophages, and some granulocytes [18], were increased in smokers with and without chronic obstructive pulmonary disease (COPD)
Of interest CD62E þ, which is promptly expressed after activation by inflammatory stimuli [21,22,23,24], might have been induced by the irritation produced by the bronchoscopy itself, which would indicate that CD62E þ MVs are likely derived from pulmonary endothelium

Summary

Introduction

Cell-to-cell communication is an essential component for mammalian development and preservation of homeostasis and for efficient responses to threats within the surrounding environment. Beyond signaling through cell-cell contact, extracellular vesicles (EVs) have recently emerged as important information shuttles that can disseminate homeostatic and disease signals [1]. It has become increasingly clear that these vesicles, originally considered cell debris, are actively involved in a variety of physiologically relevant processes and participate in cell-cell communication. Vesicles released by healthy cells are found in circulation and contain cell-derived biomolecules such as miRNA, cytokines, and inflammatory mediators [1]. Most cells in blood are thought to release EVs [1]; studies in blood have practical difficulties both in assaying the low EV concentrations in circulation and identifying their tissue of origin [2]. Studies of EVs in cancer, cardiovascular, metabolic, neurological, and infectious diseases among others have started to illuminate a role for EVs as promising candidate biomarkers for diagnosis and prognosis in lung diseases [3]

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