Diesel exhaust particles dysregulate multiple immunological pathways in murine macrophages: Lessons from microarray...

Area of Science:

• Environmental Health
• Immunology
• Molecular Biology

Background:

• Ambient particulate matter exposure is linked to cardiovascular diseases.
• Mechanisms connecting inhaled pollutants to systemic vascular effects and atherosclerosis are not well understood.

Purpose of the Study:

• To investigate the role of macrophages in mediating the effects of diesel exhaust particles (DEP).
• To analyze gene expression patterns in macrophages exposed to DEP in vitro and in vivo.

Main Methods:

• Gene expression analysis using Affymetrix microarrays in cultured peritoneal macrophages (in vitro).
• Single-cell RNA sequencing (scRNA-seq) of alveolar macrophages from DEP-exposed mice (in vivo).
• Treatment of mouse peritoneal macrophages with a DEP methanol extract (DEPe).

Main Results:

• DEPe exposure significantly altered gene expression in peritoneal macrophages, enriching immune response and antioxidant defense pathways.
• Heme oxygenase 1 (Hmox1) was the most significantly upregulated gene in vitro.
• scRNA-seq revealed significant gene dysregulation and heterogeneity in alveolar macrophage responses to DEP in vivo, with enrichment in immune system pathways.

Conclusions:

• Diesel exhaust particles (DEP) dysregulate immunological pathways in macrophages.
• These DEP-induced changes in macrophages may contribute to the development of pulmonary and systemic vascular effects.
• Macrophages play a key role in translating inhaled particulate matter exposure into systemic health impacts.