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Updated: Aug 8, 2026
In Vivo Assessment of Alveolar Macrophage Efferocytosis Following Ozone Exposure
Published on: October 22, 2019
Effects of select PM-associated metals on alveolar macrophage phosphorylated ERK1 and -2 and iNOS expression during
Colette Prophete1, Polina Maciejczyk, Konstantin Salnikow
1NYU-EPA Particulate Matter Health Research Center, Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, USA.
Abstract:
It was hypothesized that relative mass relationships among select constituent metals and iron (Fe3+) govern the pulmonary immunotoxic potential of any PM(2.5) sample, as these determine the extent to which Fe3+ binding by transferrin is affected (resulting in altered alveolar macrophage [AM] Fe status and subsequent antibacterial function). Iron response protein (IRP) binding activity is a useful indirect measurement of changes in Fe status, as reductions in cell Fe levels lead to increases in IRP binding. However, AM IRP activity can be affected by an increased presence of nitric oxide generated by inducible nitric oxide synthase (iNOS). This study sought to determine if any changes in AM IRP activity induced by PM(2.5) constituents V, Mn, or Al were independent from effects of the metals on cell NO formation. NR8383 rat AM were exposed to Fe3+ alone or combined with V, Mn, or Al at metal:Fe ratios representative of those in PM(2.5) collected in New York City, Los Angeles, and Seattle during fall 2001. Cells were then assessed for changes in IRP activity and iNOS expression. Phosphorylated extracellular signal-regulated kinase (ERK) 1 and 2 levels were also measured since activated ERKs are involved in signaling pathways that lead to increased iNOS expression. The results indicate that V and Al, and to a lesser extent Mn, altered IRP activity, though the effects were not consistently concentration dependent. Furthermore, while V and Mn treatments did not induce iNOS expression, Al did. These results confirmed our hypothesis that certain metals associated with PM(2.5) might alter the pulmonary immunocompetence of exposed hosts by affecting the Fe status of AM, a major class of deep lung defense cells.
Insights
Metals in fine particulate matter (PM2.5) can impact lung immunity by altering iron (Fe) levels in alveolar macrophages (AM). This study found that vanadium (V), aluminum (Al), and manganese (Mn) affect AM iron status and function.
Area of Science:
- Environmental Health
- Toxicology
- Immunology
Background:
- Fine particulate matter (PM2.5) contains metals that may affect lung immune cells.
- Iron (Fe) status in alveolar macrophages (AM) is crucial for their antibacterial function.
- Metal-protein interactions, particularly with transferrin, can alter cellular Fe levels.
Purpose of the Study:
- To investigate if metals in PM2.5 (V, Mn, Al) alter AM iron status independently of nitric oxide (NO) production.
- To determine the impact of these metals on iron response protein (IRP) binding activity in AM.
- To assess the relationship between metal exposure, AM iron status, and inducible nitric oxide synthase (iNOS) expression.
Main Methods:
- NR8383 rat AM were exposed to Fe3+ alone or with V, Mn, or Al at PM2.5-relevant ratios.
- Assessed changes in AM IRP binding activity as an indicator of Fe status.
- Measured iNOS expression and phosphorylated extracellular signal-regulated kinase (ERK) 1/2 levels to evaluate NO formation pathways.
Main Results:
- V, Al, and to a lesser extent Mn, altered AM IRP activity, indicating changes in Fe status.
- Effects on IRP activity were not consistently concentration-dependent.
- Al exposure induced iNOS expression, while V and Mn did not.
Conclusions:
- Metals like V, Al, and Mn in PM2.5 can impair pulmonary immunocompetence by altering AM Fe status.
- These findings support the hypothesis that metal-Fe interactions in PM2.5 influence AM function and host defense.
