【Introduction】Exosomes are small (50-150 nm) membrane vesicles of endocytic origin, which are found in bodying fluids, and supporting their role in intercellular communication. Although recent studies have demonstrated that various biomarkers involved in the extent of pain from the serum exosomes, the effects of exosomes on pain have not been elucidated. We have previously demonstrated that increased expression of complement C5 on exosome bilayers from partial sciatic nerve ligation (PSNL) mouse sera enhances formalin-induced nociceptive behavior. In this study, to identify tissues producing complement C5 on exosome bilayers, we extracted 1) intracellular vesicles in tissues from PSNL and sham-operated groups, 2) organ-specific exosomes from serum-derived exosomes by immunoprecipitation, and compared the protein expression levels.
【Results and Discussion】We examined the expression levels of complement C5 in intracellular vesicles extracted from the tissues of PSNL mice were compared with those of the sham-operation group, the expression levels of complement C5 were increased in the PSNL group in the liver, but there was no difference in expression levels between the two groups in other tissues. In addition, membrane proteins expressed on the bilayer of intracellular vesicles extracted from the liver of PSNL mice were scraped off by trypsin treatment, the complement C5 expression level was significantly reduced. On the other hand, liver-derived exosomes were purified from serum-derived exosomes, and complement C5 expression levels were compared between the PSNL mouse group and the sham-operated group, resulting in a significant increase in complement C5 expression levels in the PSNL mouse group. These results suggest that complement C5, which was upregulated on exosome bilayers from PSNL mouse serum, is of liver origin.