Gestational exposure to titanium dioxide, diesel exhaust, and concentrated urban air particles affects levels of specialized pro-resolving mediators in response to allergen in asthma-susceptible neonate lungs

ABSTRACT

Maternal gestational exposures to traffic and urban air pollutant particulates have been linked to increased risk and/or worsening asthma in children; however, mechanisms underlying this vertical transmission are not entirely understood. It was postulated that gestational particle exposure might affect the ability to elicit specialized proresolving mediator (SPM) responses upon allergen encounter in neonates. Lipidomic profiling of 50 SPMs was performed in lungs of neonates born to mice exposed to concentrated urban air particles (CAP), diesel exhaust particles (DEP), or less immunotoxic titanium dioxide particles (TiO2). While asthma-like phenotypes were induced with identical eosinophilia intensity across neonates of all particle-exposed mothers, levels of LXA4, HEPE and HETE isoforms, and HDoHe were only decreased by CAP and DEP only but not by TiO2. However, RvE2 and RvD1 were inhibited by all particles. In contrast, isomers of Maresin1 and Protectin D1 were variably elevated by CAP and DEP, whereas Protectin DX, PGE2, and TxB2 were increased in all groups. Only Protectin D1/DX, MaR1(n-3,DPA), 5(S),15(S)-DiHETE, PGE2, and RvE3 correlated with eosinophilia but the majority of other analytes, elevated or inhibited, showed no marked correlation with inflammation intensity. Evidence indicates that gestational particle exposure leads to both particle-specific and nonspecific effects on the SPM network.

KEYWORDS:

• Titanium dioxide particles
• diesel exhaust particles
• concentrated urban air particles
• specialized pro-resolving mediators
• asthma

Abbreviations

5S,15S-diHETE = 5S,15S-dihydroxy-eicosa-6E,8Z,11Z,13E-tetraenoic acid

10S,17S-DiHDoHE = 10,17-dihydroxydocosahexaenoic acid

HDoHE = hydroxydocosahexaenoic acid

HETE = hydroxyeicosatetraenoic acid

HEPE = hydroxyeicosapentaenoic acid

LX = lipoxin

TX = thromboxane

PG = prostaglandin

PD = protectin

Rv = resolvin

LT = leukotriene

TiO2 = titanium dioxide particles

DEP = diesel exhaust particles

CAP = concentrated urban air particles

SPM = specialized pro-resolving mediators

OVA = ovalbumin

PM = particulate matter

MRM = Multiple Reaction Monitoring

HPLC = high-performance liquid chromatography

LC/MS = liquid chromatography–mass spectrometry

BAL = bronchoalveolar lavage

PBS = phosphate-buffered saline

Acknowledgments

This study was supported by a National Institutes of Environmental Health Sciences (NIEHS) grant R01ES030227 to AVF and by Brown Physicians Incorporated Academic Assessment grant funds to AVF.

The Lipidomics Core at WSU was supported in part by the National Center for Research Resources, National Institutes of Health Grant S10RR027926. We thank Dr Rao Maddipati for his guidance in LC/MS lipidomics.

Data availability statement

Raw data can be available from AVF by a reasonable request through the editorial office.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary Material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This work was supported by the National Institute of Environmental Health Sciences [R01ES030227].