Microglial priming through the lung-brain axis: The role of air pollution-induced circulating factors

Christen L. Mumaw, Shannon Levesque, Constance McGraw, Sarah Robertson, Selita Lucas, Jillian E. Stafflinger, Matthew J. Campen, Pamela Hall, Jeffrey P. Norenberg, Tamara Anderson, Amie K. Lund, Jacob D. McDonald, Andrew K. Ottens, Michelle Block

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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 O3 . Further, aging glia were more sensitive to the proinflammatory effects of O3 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.

Original languageEnglish (US)
Pages (from-to)1880-1891
Number of pages12
JournalFASEB Journal
Volume30
Issue number5
DOIs
StatePublished - May 1 2016

Fingerprint

Air Pollution
Air pollution
Brain
Chemical activation
Lung
Rats
Macrophage-1 Antigen
Neurodegenerative diseases
Cytokines
Vehicle Emissions
Microglia
Air Pollutants
Ozone
Amyloid
Serum
Aging of materials
Neuroglia
Neurodegenerative Diseases
Disease Progression

Keywords

  • Glia
  • Inhaled pollutants
  • Neuroinflammation

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Mumaw, C. L., Levesque, S., McGraw, C., Robertson, S., Lucas, S., Stafflinger, J. E., ... Block, M. (2016). Microglial priming through the lung-brain axis: The role of air pollution-induced circulating factors. FASEB Journal, 30(5), 1880-1891. https://doi.org/10.1096/fj.201500047

Microglial priming through the lung-brain axis : The role of air pollution-induced circulating factors. / Mumaw, Christen L.; Levesque, Shannon; 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.

In: FASEB Journal, Vol. 30, No. 5, 01.05.2016, p. 1880-1891.

Research output: Contribution to journalArticle

Mumaw, CL, Levesque, S, McGraw, C, Robertson, S, Lucas, S, Stafflinger, JE, Campen, MJ, Hall, P, Norenberg, JP, Anderson, T, Lund, AK, McDonald, JD, Ottens, AK & Block, M 2016, 'Microglial priming through the lung-brain axis: The role of air pollution-induced circulating factors', FASEB Journal, vol. 30, no. 5, pp. 1880-1891. https://doi.org/10.1096/fj.201500047
Mumaw CL, Levesque S, McGraw C, Robertson S, Lucas S, Stafflinger JE et al. Microglial priming through the lung-brain axis: The role of air pollution-induced circulating factors. FASEB Journal. 2016 May 1;30(5):1880-1891. https://doi.org/10.1096/fj.201500047
Mumaw, Christen L. ; Levesque, Shannon ; 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. / Microglial priming through the lung-brain axis : The role of air pollution-induced circulating factors. In: FASEB Journal. 2016 ; Vol. 30, No. 5. pp. 1880-1891.
@article{05cb4596a1434d5da354027d3d75c884,
title = "Microglial priming through the lung-brain axis: The role of air pollution-induced circulating factors",
abstract = "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 O3 . Further, aging glia were more sensitive to the proinflammatory effects of O3 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.",
keywords = "Glia, Inhaled pollutants, Neuroinflammation",
author = "Mumaw, {Christen L.} and Shannon Levesque and Constance McGraw and Sarah Robertson and Selita Lucas and Stafflinger, {Jillian E.} and Campen, {Matthew J.} and Pamela Hall and Norenberg, {Jeffrey P.} and Tamara Anderson and Lund, {Amie K.} and McDonald, {Jacob D.} and Ottens, {Andrew K.} and Michelle Block",
year = "2016",
month = "5",
day = "1",
doi = "10.1096/fj.201500047",
language = "English (US)",
volume = "30",
pages = "1880--1891",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "5",

}

TY - JOUR

T1 - Microglial priming through the lung-brain axis

T2 - The role of air pollution-induced circulating factors

AU - Mumaw, Christen L.

AU - Levesque, Shannon

AU - McGraw, Constance

AU - Robertson, Sarah

AU - Lucas, Selita

AU - Stafflinger, Jillian E.

AU - Campen, Matthew J.

AU - Hall, Pamela

AU - Norenberg, Jeffrey P.

AU - Anderson, Tamara

AU - Lund, Amie K.

AU - McDonald, Jacob D.

AU - Ottens, Andrew K.

AU - Block, Michelle

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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 O3 . Further, aging glia were more sensitive to the proinflammatory effects of O3 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.

AB - 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 O3 . Further, aging glia were more sensitive to the proinflammatory effects of O3 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.

KW - Glia

KW - Inhaled pollutants

KW - Neuroinflammation

UR - http://www.scopus.com/inward/record.url?scp=84966388997&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84966388997&partnerID=8YFLogxK

U2 - 10.1096/fj.201500047

DO - 10.1096/fj.201500047

M3 - Article

C2 - 26864854

AN - SCOPUS:84966388997

VL - 30

SP - 1880

EP - 1891

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 5

ER -