Extracellular vesicles released in response to respiratory exposures: implications for chronic disease

Figures & data

Table 1. Key properties of exosomes and microvesicles.

	Exosomes	Microvesicles
Alternative nomenclature	Extracellular vesicles	Extracellular vesicles, microparticles, ectosomes
Subcellular origin	Multivesicular endosomes	Plasma membrane
Diameter	50–150 nm	100–1000 nm
Sedimentation speed	100,000 × g	10,000 × g
Molecular markers	Tetraspanins (e.g., CD63, CD81,CD9), ESCRT proteins (TSG101, Alix),	Phosphatidylserine, integrins, selectins
Detection	NTA, TRPS, bead-based flow cytometry, fluorescence-triggered flow cytometry	Conventional scatter-triggered flow cytometry

ESCRT: endosomal complex required for transport; NTA: nanoparticle tracking analysis; TRPS: tunable resistive pulse sensing.

Table 2. Overview of surface molecules that are commonly used to identify the cellular origin of microvesicles in complex biological fluids such as plasma.

Cellular origin	Marker proteins
Endothelial	CD105, CD62E, CD146
Endothelial/platelet	CD31, CD144, CD51
Platelet	CD41, CD42a, CD42b, CD61
Epithelial	CD326
Total leukocytes	CD45
Monocyte/macrophage	CD14
Neutrophil	MPO, CD66
Erythrocyte	Ter119
T cell	CD154

Figure 1. Results of the literature search. The graphs show the number of publications (A) per year since the first publication in 2004 (B) that report on in vitro, human and animal experiments, (C) according to the biological material in which EV were studied, (D) according to the EV nomenclature used by the authors, (E) that used a specific EV characterization technique, (F) that used a specific EV isolation technique, (G) that investigated and confirmed the involvement of respiratory exposure-induced EV in the specified biological processes, and (H) according to the pathology for which the authors considered the described changes to be relevant.

Figure 2. Schematic representation of how respiratory exposure-induced EV may contribute to the pathogenesis of chronic diseases. Respiratory toxicants arise from CS, as well as occupational or environmental sources. Upon inhalation, they come in contact with several cell types of the lungs, including epithelial cells, endothelial cells, alveolar macrophages, monocytes, and circulating blood cells. Exposure to respiratory toxicants causes increased release and altered composition of EV from different cellular sources. The respiratory exposure-induced EV may either remain in the lung lumen or are disseminated via the blood circulation. Locally at the site of exposure as well as systemically, they may promote inflammation, hypercoagulability, endothelial dysfunction, tissue remodeling, and angiogenesis, all of which are interrelated and can further enhance each other. By promoting these biological processes, EV may contribute to the mechanistic link between respiratory exposures and the pathogenesis of respiratory exposure-associated diseases such as COPD, CVD, asthma, and lung cancer. For each biological process, the diseases are sorted according to the strength of evidence for involvement of the respective process in their pathogenesis. This figure contains elements from Servier Medical Art.