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Role of alveolar macrophages in lipopolysaccharide-induced neutrophil accumulation
1Trudeau Institute, Inc., Saranac Lake, New York 12983.
Abstract:
B6D2F1/TRU mice were exposed to a lipopolysaccharide (LPS) aerosol that resulted in a 1-h-postexposure lung burden of about 290 ng of LPS. This exposure caused an accumulation of neutrophils in the lung that peaked between 6 and 12 h after exposure. To determine the potential role of alveolar macrophages (AM) in the induction of neutrophil accumulation by LPS, 10(6) AM from normal or LPS-exposed mice were transferred to the lungs of groups of naive recipient mice. A third group of mice was instilled intratracheally with vehicle only. After 5 h, the lungs of the mice were lavaged and the numbers of neutrophils in the lavage fluids were determined. The instillation of AM from unexposed mice did not cause significantly more neutrophils to accumulate than did the instillation of vehicle only, whereas the instillation of AM from LPS-exposed mice caused nearly a threefold increase in the numbers of neutrophils in lavage fluids. Transfer of AM from LPS-exposed mice into cutaneous air pouches of naive mice also caused greater local neutrophil accumulation (10-fold) than did the transfer of AM from normal mice. Repeated freeze-thawing of the suspensions of AM before transfer to recipients significantly reduced the ability of the suspensions to induce neutrophil accumulation. This indicated that AM viability is necessary to cause a maximal neutrophil infiltration upon transfer of the AM. To determine the extent to which LPS-induced neutrophil accumulation depends on the presence of AM, the ability of LPS to elicit neutrophil accumulation when injected alone or together with AM into air pouches was determined. The injection of either AM or LPS alone caused few neutrophils to accumulate, whereas the injection of LPS and AM together caused a large number of neutrophils to accumulate. The results of this study indicate that LPS deposition in the lung can stimulate AM to induce neutrophil accumulation and that this may be the major mechanism by which LPS causes neutrophil accumulation.
Insights
Lipopolysaccharide (LPS) exposure stimulates alveolar macrophages (AM) to induce neutrophil accumulation in the lungs. This study shows AM are crucial for LPS-induced neutrophil infiltration, highlighting a key inflammatory mechanism.
Area of Science:
- Immunology
- Pulmonary Medicine
- Cell Biology
Background:
- Lipopolysaccharide (LPS) aerosol exposure in mice leads to significant neutrophil accumulation in the lungs.
- The precise role of alveolar macrophages (AM) in mediating LPS-induced neutrophil recruitment remains to be fully elucidated.
Purpose of the Study:
- To investigate the potential role of alveolar macrophages (AM) in the induction of neutrophil accumulation following lipopolysaccharide (LPS) exposure.
- To determine if AM viability is essential for mediating LPS-induced neutrophil infiltration.
Main Methods:
- Transfer of AM from LPS-exposed or normal mice into naive recipient mice lungs and air pouches.
- Assessment of neutrophil accumulation in lung lavage fluid and air pouch exudates.
- Evaluation of AM viability by freeze-thawing suspensions before transfer.
- Co-injection of LPS and AM into air pouches to assess synergistic effects on neutrophil accumulation.
Main Results:
- Transfer of AM from LPS-exposed mice significantly increased neutrophil accumulation compared to AM from normal mice or vehicle control.
- AM viability was essential for maximal neutrophil infiltration upon transfer.
- Co-administration of LPS and AM resulted in a synergistic, large-scale neutrophil accumulation, whereas either substance alone had minimal effect.
Conclusions:
- LPS deposition in the lung stimulates alveolar macrophages (AM) to induce neutrophil accumulation.
- Alveolar macrophages play a major role in the mechanism of LPS-induced neutrophil accumulation in the lung.
- AM viability is critical for this inflammatory response.