Ectosomes as immunomodulators

Abstract

Considerable progress has been made in recognizing microvesicles as important mediators of intercellular communication rather than irrelevant cell debris. Microvesicles released by budding directly from the cell membrane surface (i.e., ectocytosis) either spontaneously or in response to various stimuli are called shed vesicles or ectosomes. Ectosomes are rightside-out vesicles with cytosolic content, and they expose phosphatidylserine in the outer leaflet of their membrane. Depending on their cellular origin, ectosomes have been associated with a broad spectrum of biological activities. In the light of recent findings, we now know that ectosomes derived from polymorphonuclear leukocytes, erythrocytes, platelets, and tumor cells have profound effects on the innate immune system, as well as on the induction of the adaptive immunity, globally reprogramming cells such as macrophages or dendritic cells toward an immunosuppressive and possibly tolerogenic phenotype. Although the effects observed in the circulation are mainly procoagulant and pro-inflammatory, ectosomes might be anti-inflammatory/immunosuppressive in local inflammation.

Cell-Cell Communication Via Extracellular Membrane Vesicles and Its Role in the Immune Response

“…Biogenesis and molecular composition of ectosomes Ectosomes are a class of extracellular membrane vesicles with the size of 50-200 nm in diameter (Sadallah et al, 2011). They are generated by budding directly out of the plasma membrane (Scolding et al, 1989).…”

“…As with exosomes, the biological roles of ectosomes are highly pleiotropic and dependent on their origins and types of recipient cells (Sadallah et al, 2011). Ectosomes from endothelial cells and monocytes are known to have pro-inflammatory properties, which is mediated in part by IL-1 in the ectosomes.…”

Changing world of neutrophils

“…Most of the data on PMN-derived EVs (called in these studies ectosomes) come from the laboratory of Dr. Schifferli [26,[34][35][36]39,40,45,[93][94][95][96]. They characterized the size and surface properties of EVs released upon fMLP-stimulation and came to the conclusion that both the in vitro and the in vivo generated EVs are right-side out [39,45].…”

The involvement of cation leaks in the storage lesion of red blood cells

“…Indeed, vesicular transfer of glycosylphosphatidylinositol-linked proteins has been shown to occur, correcting the defect in paroxysmal nocturnal hemoglobinuria (PNH) RBCs (Sloand et al, 1998, 2004). These right-side out vesicles are also implicated in inflammatory and immunomodulatory responses to transfusion (Sadallah et al, 2008, 2011; Kriebardis et al, 2012). …”