Microparticles released by Ectocytosis from Human Neutrophils: Characterisation, Properties and Functions

摘要: The field of microparticles (MPs) has gained growing interest over the last decade. Numbers papers have come out recently describing molecular or functional characteristics MPs derived from various cells, suggesting in vivo roles for other than being inert side-products cellular activation. The properties and released surface activated human polymorphonuclear neutrophils (PMN), called ectosomes, will be discussed Part I. implications these with regards to interaction PMN-ectosomes, particular macrophages, their circulation blood addressed II III, respectively. As presented I, many neutrophil-derived membrane proteins were translocated ectosomes. There was no positive negative selection transmembrane type versus glycophosphatidylinositol-linked proteins. Indeed, both types had representatives present absent on In addition, ectosomes exposed several active enzymes surface, such as proteinase-3, myeloperoxidase, elastase matrix metalloproteinase-9. fact that are unable maintain asymmetry bilayer illustrated by presence phosphatidylserine outer leaflet. Ectosomes also found bind first component classical pathway complement, C1q; an additional finding been looked at more detail III. Binding assays revealed affinity endothelial cells well macrophages. Further analyses between PMN monocyte macrophages (HMDM) provided data do not only bind, but subsequently phagocytosed HMDM. sole binding however, sufficient induce anti-inflammatory reprogramming particular, dose-dependently counteracted pro-inflammatory response HMDM stimuli zymosan LPS. This effect comprised early increase release cytokine TGFβ1 subsequent downregulation IL-8, IL-10 TNFα secretion. Data obtained using neutralising anti-TGFβ antibodies suggested phenomena might causally linked, least partially. As alluded above, C1q. activate fix complement. C3- C4-fragments detected after incubation normal serum. Using C1q- C2-deficient serum, ectosome-induced activation complement could mainly attributed pathway. Finally, opsonisation induced immune adherence erythrocytes. These suggest blood-borne sequestered erythrocytes, a mechanism drive clearance circulation, similarly complexes.