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

• Published in: The FASEB journal Vol. 31; no. 9; p. 3950
• Main Authors: Erickson, Michelle A, Jude, Joseph, Zhao, Hengjiang, Rhea, Elizabeth M, Salameh, Therese S, Jester, William, Pu, Shelley, Harrowitz, Jenna, Nguyen, Ngan, Banks, William A, Panettieri, Jr, Reynold A, Jordan-Sciutto, Kelly L
• Format: Journal Article
• Language: English
• Published: United States 01.09.2017
• Subjects: Acute-Phase Proteins - genetics; Acute-Phase Proteins - metabolism; Animals; Brain Diseases - chemically induced; Brain Diseases - metabolism; Cytokines - blood; Cytokines - genetics; Cytokines - metabolism; Female; Inflammation - blood; Inflammation - chemically induced; Inflammation - metabolism; Liver - metabolism; Lung Diseases - chemically induced; Mice; Mice, Inbred BALB C; Ozone - toxicity; Serum Amyloid A Protein - metabolism; blood-brain barrier; air pollution; cytokines; acute-phase proteins; microglia
• ISSN: 1530-6860
• DOI: 10.1096/fj.201600857RRR

Accumulating evidence suggests that O exposure may contribute to CNS dysfunction. Here, we posit that inflammatory and acute-phase proteins in the circulation increase after O exposure and systemically convey signals of O exposure to the CNS. To model acute O exposure, female Balb/c mice were exposed to 3 ppm O 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 O 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 O -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-O exposure. Our findings suggest that A-SAA is functionally linked to pulmonary inflammation in our O exposure model and that A-SAA could be an important systemic signal of O 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.