EVS appeared to be enriched in cholesterol, sphingomyelin, and ganglioside GM3, lipids that are typically concentrated in detergent-resistant membranes. LEVS of HIV-1-infected and -uninfected lymphocytic H9 cells were evaluated by Li et al. [61]. Using the technique of stable isotope labeling by amino acids in cell culture (SILAC), the authors compared protein expression patterns in the EVS compartment of HIV-1-infected

and -uninfected lymphocytes. Fourteen proteins were found to be differentially expressed in the LEVS fraction of HIV-1-infected cells versus -uninfected controls. Three immunomodulatory molecules Nintedanib datasheet were reproducibly identified and included ADP-ribosyl cyclase 1 (CD38), l-lactate dehydrogenase B chain, and annexin V. This study revealed that LEVS released EPZ5676 ic50 from HIV-1-infected cells are composed of a unique and quantitatively different protein signature and harbor regulatory molecules that impact the processes of cellular apoptosis. In patients with B-cell malignancy, accumulation of LEVS have been observed and analyzed using proteomic tools by Miguet et al., in order to identify specific biomarker capable of diagnosing difficult cases such as leukemic phase of

non-Hodgkin lymphoma [90] and [91]. These studies allowed the identification CD148, a membrane receptor with phosphatase activity, as a discriminating biomarker candidate. For confirmation purposes, flow cytometry

analyses were performed on 158 patients and 30 controls revealing that CD148 was overexpressed in mantle cell lymphoma as compared to other B-cell neoplasms. Until now, a few proteomic studies have been published on the proteome of EEVS. Nevertheless, EEVS have been characterized at the proteome level by Banfi et al. [92]. Mass spectrometry analyses revealed the presence of newly described proteins such as metabolic enzymes, proteins involved in adhesion and fusion Molecular motor processes, members of protein folding event, cytoskeleton associated proteins and nucleosome. In an interesting study, Liu et al. provided information not only on proteomics of EEVS but also on the changes of the protein content in the endothelial cells after stimulation and EEVS release [93]. A direct correlation between the proteins that form EEVS and tumor necrosis factor-α-activated endothelial cells was observed. The biology of REVS, PEVS, LEVS, and of EEVS is dependent of the cells from which they originate. Nevertheless, many physiological properties, such as their role in fibrinolysis, may be shared by EVS deriving from different cellular origin, as demonstrated for LEVS and EEVS.