Inflammatory Stroke Extracellular Vesicles Induce Macrophage Activation
Couch Y., Akbar N., Davis S., Fischer R., Dickens AM., Neuhaus AA., Burgess AI., Rothwell PM., Buchan AM.
Background and Purpose— Extracellular vesicles (EVs) are protein–lipid complexes released from cells, as well as actively exocytosed, as part of normal physiology, but also during pathological processes such as those occurring during a stroke. Our aim was to determine the inflammatory potential of stroke EVs. Methods— EVs were quantified and analyzed in the sera of patients after an acute stroke (<24 hours; OXVASC [Oxford Vascular Study]). Isolated EV fractions were subjected to untargeted proteomic analysis by liquid chromatography mass-spectrometry/mass-spectrometry and then applied to macrophages in culture to investigate inflammatory gene expression. Results— EV number, but not size, is significantly increased in stroke patients when compared to age-matched controls. Proteomic analysis reveals an overall increase in acute phase proteins, including C-reactive protein. EV fractions applied to monocyte-differentiated macrophage cultures induced inflammatory gene expression. Conclusions— Together these data show that EVs from stroke patients are proinflammatory in nature and are capable of inducing inflammation in immune cells.