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Comparison of the responses of alveolar macrophages from rats, mice and humans following particle overload [2nd exp]

ABSTRACT: Chromic inhalation of poorly soluble low toxicity particles, like titanium dioxide or carbon black, at high exposure levels leading to particle overload in alveolar macrophages, can induce chronic inflammation and lung cancer in rats, but not in mice. Whether this rat adverse response is predictive for humans remains unsettled for more than 40 years. In order to clarify the human relevance of the adverse rat response to particle overload, primary rat, mouse and human alveolar macrophages were exposed in vitro to overload of titanium dioxide or carbon black particles, and their activation profile was analyzed by RNAseq. We report, here, a robust transcriptomic signature of poorly soluble low toxicity particle overload in rat alveolar macrophages in vitro ,which was not observed in mouse macrophages. A similar but markedly lower response was recorded in human macrophages.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE272350 | GEO | 2025/04/30

REPOSITORIES: GEO

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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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Comparison of the responses of alveolar macrophages from rats, mice and humans following particle overload [2nd exp]

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