Serum amyloid A: an ozone-induced circulating factor with potentially important functions in the lung-brain axis

Abstract

Accumulating evidence suggests that O₃ exposure may contribute to CNS dysfunction. Here, we posit that inflammatory and acute-phase proteins in the circulation increase after O₃ exposure and systemically convey signals of O₃ exposure to the CNS. To model acute O₃ exposure, female Balb/c mice were exposed to 3 ppm O₃ or forced air for 2 h and were studied after 6 or 24 h. Of 23 cytokines and chemokines, only KC/CXCL1 was increased in blood 6 h after O₃ exposure. The acute-phase protein serum amyloid A (A-SAA) was significantly increased by 24 h, whereas C-reactive protein was unchanged. A-SAA in blood correlated with total leukocytes, macrophages, and neutrophils in bronchoalveolar lavage from O₃-exposed mice. A-SAA mRNA and protein were increased in the liver. We found that both isoforms of A-SAA completely crossed the intact blood-brain barrier, although the rate of SAA2.1 influx was approximately 5 times faster than that of SAA1.1. Finally, A-SAA protein, but not mRNA, was increased in the CNS 24 h post-O₃ exposure. Our findings suggest that A-SAA is functionally linked to pulmonary inflammation in our O₃ exposure model and that A-SAA could be an important systemic signal of O₃ exposure to the CNS.-Erickson, M. A., Jude, J., Zhao, H., Rhea, E. M., Salameh, T. S., Jester, W., Pu, S., Harrowitz, J., Nguyen, N., Banks, W. A., Panettieri, R. A., Jr., Jordan-Sciutto, K. L. Serum amyloid A: an ozone-induced circulating factor with potentially important functions in the lung-brain axis.

Keywords: acute-phase proteins; air pollution; blood-brain barrier; cytokines; microglia.