Diesel Exhaust Particles Remodel Lipid Raft-Associated Molecular Features Potentially Relevant to SARS-CoV-2...

Area of Science:

• Environmental Health
• Molecular Biology
• Cell Biology

Background:

• Geographic overlap of COVID-19 and pollution suggests links between particulate matter and severe disease.
• Lipid rafts are crucial for viral entry, with SARS-CoV-2 spike protein interacting with gangliosides GM1 and GM2.
• ACE2 (angiotensin-converting enzyme 2) is a key receptor for SARS-CoV-2, and its interaction with the spike protein is vital for viral entry.

Purpose of the Study:

• To investigate the effects of diesel exhaust particle (DEP) exposure on A549 alveolar lung cells.
• To determine how DEP exposure influences the localization of ACE2 and the expression of ADAM17.
• To analyze changes in inflammatory markers (IL-6, IL-8) and lipid raft composition following DEP exposure.

Main Methods:

• Exposure of A549 cells to DEP.
• Analysis of ACE2 and ADAM17 localization within lipid rafts.
• Measurement of cytokine release (IL-6, IL-8) and soluble ACE2 (sACE2).
• Lipidomic analysis using UHPLC-MS to assess ganglioside composition.

Main Results:

• DEP exposure caused ACE2 to shift into lipid rafts and increased immature ADAM17.
• Significant increase in IL-6 release observed, with no changes in IL-8 or sACE2.
• DEP exposure altered ganglioside composition, increasing GM2 and decreasing GM1 and GM3 levels.
• No significant changes in COX-2 or HO-1 protein levels or membrane redistribution.

Conclusions:

• DEP exposure remodels lipid raft-associated molecular features in lung cells, including ACE2 redistribution and altered ganglioside profiles.
• Increased IL-6 release suggests DEP contributes to inflammation.
• These cellular changes may be relevant to SARS-CoV-2 susceptibility, but direct viral interaction was not assessed.