# Differential responses of males and females to multi-walled carbon nanotubes

> **NIH NIH R21** · UNIVERSITY OF MONTANA · 2021 · $182,034

## Abstract

Abstract
Adverse outcomes following the inhalation of engineered nanomaterials, such as multi-walled carbon nanotubes
(MWCNTs), have been identified in occupational settings. Unfortunately, long-term consequences and sensitive
populations remain undefined. Chronic respiratory diseases often demonstrate sex-biases in disease
prevalence. For example, asthma occurs more often and with increased severity in adult women compared to
men. Our preliminary studies indicate that the outcomes of MWCNT exposure follow this trend: there is increased
lung inflammation and injury in females compared to males. Therefore, it is logical and necessary to investigate
the biological factors that may contribute to these sex-differences. There is experimental and clinical evidence
that sex-steroid hormones influence the development of lung disease. A likely target of hormone signaling is
alveolar macrophages (AMs), the primary resident immune cell within the lungs. The phenotype and function of
AMs is an important factor in promoting specific immune responses to inhaled materials, and may contribute to
inadvertent immune-mediated lung injury. This project will investigate the role of hormone signaling on AM
phenotype and how this contributes to impaired lung function after exposure to MWCNTs. Current literature
suggests that estrogen receptor a (ERa) signaling promotes an exaggerated M2a macrophage phenotype. The
M2a phenotype promotes antibody production by B cells and is therefore associated with allergy and asthma;
MWCNTs have also been shown to induce an M2a phenotype in AMs. Amplification of M2a phenotype
polarization can lead to increased production of signaling molecules that cause inappropriate immune cell
recruitment and inflammation, which eventually results in increased lung injury and decreased function. These
data, combined with our preliminary results, provides a potential hormone-dependent mechanism for the
increased susceptibility of women to allergens and nanomaterials. This project will address the hypothesis that
estrogen signaling through ERa promotes an exaggerated M2a phenotype in female AMs, which contributes to
the increased occurrence and severity of particle-induced respiratory diseases in women.

## Key facts

- **NIH application ID:** 10266754
- **Project number:** 5R21ES030978-02
- **Recipient organization:** UNIVERSITY OF MONTANA
- **Principal Investigator:** Andrij Holian
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $182,034
- **Award type:** 5
- **Project period:** 2020-09-18 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10266754

## Citation

> US National Institutes of Health, RePORTER application 10266754, Differential responses of males and females to multi-walled carbon nanotubes (5R21ES030978-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10266754. Licensed CC0.

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