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Pulmonary exposure to particles during pregnancy causes increased neonatal asthma susceptibility.

ABSTRACT: Maternal immune responses can promote allergy development in offspring, as shown in a model of increased susceptibility to asthma in babies of ovalbumin (OVA)-sensitized and -challenged mother mice. We investigated whether inflammatory responses to air pollution particles (diesel exhaust particles, DEP) or control "inert" titanium dioxide (TiO(2)) particles are enhanced during pregnancy and whether exposure to particles can cause increased neonatal susceptibility to asthma. Pregnant BALB/c mice (or nonpregnant controls) received particle suspensions intranasally at Day 14 of pregnancy. Lung inflammatory responses were evaluated 48 hours after exposure. Offspring of particle- or buffer-treated mothers were sensitized and aerosolized with OVA, followed by assays of airway hyperresponsiveness (AHR) and allergic inflammation (AI). Nonpregnant females had the expected minimal response to "inert" TiO(2). In contrast, pregnant mice showed robust and persistent acute inflammation after both TiO(2) and DEP. Genomic profiling identified genes differentially expressed in pregnant lungs exposed to TiO(2). Neonates of mothers exposed to TiO(2) (and DEP, but not PBS) developed AHR and AI, indicating that pregnancy exposure to both "inert" TiO(2) and DEP caused increased asthma susceptibility in offspring. We conclude that (1) pregnancy enhances lung inflammatory responses to otherwise relatively innocuous inert particles; and (2) exposures of nonallergic pregnant females to inert or toxic environmental air particles can cause increased allergic susceptibility in offspring.

SUBMITTER: Fedulov AV

PROVIDER: S-EPMC2176127 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

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Pulmonary exposure to particles during pregnancy causes increased neonatal asthma susceptibility.

Fedulov Alexey V AV Leme Adriana A Yang Zhiping Z Dahl Morten M Lim Robert R Mariani Thomas J TJ Kobzik Lester L

American journal of respiratory cell and molecular biology 20070726 1

Maternal immune responses can promote allergy development in offspring, as shown in a model of increased susceptibility to asthma in babies of ovalbumin (OVA)-sensitized and -challenged mother mice. We investigated whether inflammatory responses to air pollution particles (diesel exhaust particles, DEP) or control "inert" titanium dioxide (TiO(2)) particles are enhanced during pregnancy and whether exposure to particles can cause increased neonatal susceptibility to asthma. Pregnant BALB/c mice ...[more]

PMID: 17656681

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Project description:BackgroundThe increasing magnitude of the opioid crisis and rising rates of neonatal abstinence syndrome (NAS) diagnoses highlight the need for increased research into how maternal substance use during pregnancy can impact the neonatal immune profile and its functionality. We hypothesized that neonates with opioid exposure would have reduced proportions of some immune cells, an anti-inflammatory cytokine profile, reduced T cell proliferation, and monocyte bacterial killing activity compared to the control population.MethodsThe present study compares immune cell populations, inflammatory and anti-inflammatory cytokine and chemokine levels in the serum, and monocyte and T cell functional activity using umbilical cord samples from neonates with known opioid exposure during gestation and from control neonates without known exposure.ResultsOur findings demonstrated a significant reduction in neutrophils, decreased levels of inflammatory cytokines in the serum, and reduced IL-2 production during in vitro CD4+ T cell proliferation in neonates exposed to opioids compared to controls. The neutrophil findings were supported by retrospective analysis of an extended network of deidentified patient records.ConclusionsThis study is the first of its kind to evaluate differences in neonatal immunity as a result of opioid exposure in the human population that will inform continued mechanistic studies.ImpactThe opioid epidemic has become a public health crisis in the United States, and the corresponding incidence of neonatal abstinence syndrome (NAS) have risen accordingly. New research is required to understand the short and long-term health impacts of opioid exposure to the neonate. This is the first human study to investigate the immunologic profile and functionality in neonates with known opioid exposure in utero. The abundance of neutrophils and the ratio of neutrophils to lymphocytes is significantly reduced along with inflammatory cytokines and chemokines following opioid exposure during pregnancy. The immune profile in opioid-exposed neonates may promote susceptibility to infection.

Project description:Rationale: Maternal immune responses can promote allergy development in offspring. Pilot data show that neonates of mother mice exposed during pregnancy to air pollution particles have increased allergic susceptibility. Objective: We investigated whether inflammatory response to titanium dioxide (TiO2) particles earlier considered immunologically âinertâ is enhanced during pregnancy. Methods: Pregnant BALB/c mice (or non-pregnant controls) received particle suspensions intranasally at day 14 of pregnancy. Lung inflammatory responses were evaluated 19 and 48 h after exposure. Results: Pregnant mice showed robust and persistent acute inflammatory responses after exposure to TiO2, while non-pregnant females had the expected minimal responses. Genomic profiling identified genes differentially expressed in pregnant lungs exposed to TiO2. Neonates of mothers exposed to TiO2 (but not PBS) developed increased susceptibility to allergens. Conclusion: Pregnancy enhances lung inflammatory responses to otherwise relatively innocuous inert particles. Experiment Overall Design: To test whether pregnancy alters the normally minimal inflammatory response to âinertâ particles, we have administered TiO2 and DEP suspensions (50 ug/mouse) or PBS solution by intranasal insufflation to normal or pregnant E14 mice (see Figure 1B). The mice were subjected to pathologic analysis 19 or 48 hrs later. Experiment Overall Design: Respirable-size TiO2 particles were generously provided by Dr. Ian Gilmour (US EPA). Particle samples were baked at 165 0C for 3 h to eliminate endotoxin, aliquoted and stored frozen at â 80 0C. Particle suspensions (50 ug in 50 uL) or PBS solution (vehicle) were administered by single intranasal insufflation of pregnant or normal Balb/c mice under light halothane anesthesia Experiment Overall Design: Total lung RNA extraction and isolation was performed 19 hrs after exposure using a Qiagen RNAeasy Mini kit according to manufacturerâs instructions (Qiagen, Valencia, CA). RNA purity and quality were analyzed by Agilent Bioanalyzer 2100 scan. The hybridization was carried out at the Harvard Partners Genomic Center Microarray facility (Cambridge, MA) using the Affymetrix GeneChip Â® platform and Affymetrix mouse 430 2.0 chips (Affymetrix, Santa Clara, CA). Experiment Overall Design: 4 samples were analyzed in each of 4 groups: Normal PBS, Normal TiO2, Pregnant PBS and Pregnant TiO2, for a total of 16 samples.

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Pulmonary exposure to particles during pregnancy causes increased neonatal asthma susceptibility.

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Pulmonary exposure to particles during pregnancy causes increased neonatal asthma susceptibility.

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