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Microglial priming through the lung—brain axis: the role of air pollution‐induced circulating factors
Author(s) -
Mumaw Christen L.,
Levesque Shan,
McGraw Constance,
Robertson Sarah,
Lucas Selita,
Stafflinger Jillian E,
Campen Matthew J.,
Hall Pamela,
Norenberg Jeffrey P.,
Anderson Tamara,
Lund Amie K.,
McDonald Jacob D.,
Ottens Andrew K.,
Block Michelle L.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201500047
Subject(s) - proinflammatory cytokine , microglia , neuroinflammation , immunology , priming (agriculture) , immune system , neurotoxicity , medicine , chemistry , inflammation , biology , toxicity , botany , germination
Air pollution is implicated in neurodegenerative disease risk and progression and in microglial activation, but the mechanisms are unknown. In this study, microglia remained activated 24 h after ozone (O3) exposure in rats, suggesting a persistent signal from lung to brain. Ex vivo analysis of serum from O3‐treated rats revealed an augmented microglial proinflammatory response and β‐amyloid 42 (Aβ42) neurotoxicity independent of traditional circulating cytokines, where macrophage‐1 antigen‐mediated microglia proinflammatory priming. Aged mice exhibited reduced pulmonary immune profiles and the most pronounced neuroinflammation and microglial activation in response to mixed vehicle emissions. Consistent with this premise, cluster of differentiation 36 (CD36) –/– mice exhibited impaired pulmonary immune responses concurrent with augmented neuroinflammation and microglial activation in response to O 3 . Further, aging glia were more sensitive to the proinflammatory effects of O 3 serum. Together, these findings outline the lung‐brain axis, where air pollutant exposures result in circulating, cytokine‐independent signals present in serum that elevate the brain proinflammatory milieu, which is linked to the pulmonary response and is further augmented with age.—Mumaw, C. L., Levesque, S., McGraw, C., Robertson, S., Lucas, S., Stafflinger, J. E., Campen, M. J., Hall, P., Norenberg, J. P., Anderson, T., Lund, A. K., McDonald, J. D., Ottens, A. K., Block, M. L. Microglial priming through the lung‐brain axis: the role of air pollution‐induced circulating factors. FASEB J. 30, 1880–1891 (2016). www.fasebj.org