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Updated: Jun 16, 2026

Alveolar Macrophage Phagocytosis and Bacteria Clearance in Mice
Published on: March 2, 2019
Update on macrophage clearance of inhaled micro- and nanoparticles
1Institute of Anatomy, University of Bern, Bern, Switzerland. geiser@ana.unibe.ch
Background:
Lung macrophages, that is, the intravascular, interstitial, pleural, and surface macrophages, are part of the mononuclear phagocyte system. They are derived from the hematopoietic stem cell in the bone marrow with the monocytes as their putative precursors. Macrophages residing on the inner surfaces of the lungs and immersed within the lung lining layer, that is, the alveolar and the airway macrophages, are constantly exposed to the environment; it is those cells that are recognized as first line of cellular host defense.
Methods And Results:
Phagocytic uptake of inhaled and deposited particles is the main mechanism to remove insoluble micrometer-sized particles from the lung surfaces, where mucociliary transport, cough, or sneezing fail or are absent. Phagocytosis requires an intact cytoskeleton and is most efficient when mediated by Fc-receptors, but complement and scavenger receptors like MARCO and CD206 are just as important. The main pathway for the clearance of macrophage-associated particles is by mucociliary transport; to a lesser degree and species specific, particle-containing macrophages may reenter into the interstitium and go from there to the lymphatics. Inhaled nanometer-sized particles that deposit along the entire respiratory tract, however, are not efficiently phagocytosed by surface macrophages.
Conclusions:
Uptake by spontaneous or stimulated (macro-) pinocytosis or electrokinetic's phenomena may become more important. In addition, translocation of nanometer-sized particles into the interstitium and to the blood circulation brings them into contact with other fluids; altered particle properties may influence particle uptake. Moreover, translocated particles may interact with lung macrophage populations that were previously not considered of great significance for the clearance of inhaled particles.
Insights
Lung macrophages, the first line of defense, efficiently clear large particles via phagocytosis. However, nanometer-sized particles pose challenges, requiring alternative uptake and translocation mechanisms for clearance.
Area of Science:
- Immunology
- Cell Biology
- Pulmonary Medicine
Background:
- Lung macrophages, including alveolar and airway types, are key components of the mononuclear phagocyte system and serve as the initial cellular defense against environmental exposures.
- Derived from bone marrow hematopoietic stem cells via monocyte precursors, these macrophages are strategically positioned to interact with inhaled substances.
Purpose of the Study:
- To investigate the mechanisms of particle clearance by lung macrophages, focusing on differences between micrometer-sized and nanometer-sized particles.
- To explore alternative pathways for nanoparticle uptake and translocation within the lung.
Main Methods:
- The study focuses on the phagocytic capabilities of lung macrophages, involving cytoskeletal integrity, Fc-receptors, and complement/scavenger receptors (MARCO, CD206).
- It examines particle clearance pathways, including mucociliary transport, interstitial translocation, and lymphatic drainage.
- The efficiency of phagocytosis for nanometer-sized particles by surface macrophages is assessed.
Main Results:
- Phagocytosis is the primary mechanism for removing insoluble micrometer-sized particles from lung surfaces, with Fc-receptors, complement, and scavenger receptors playing crucial roles.
- Mucociliary transport is the main clearance route for particle-laden macrophages, with some species-specific translocation to lymphatics.
- Surface macrophages exhibit inefficient phagocytosis of inhaled nanometer-sized particles deposited throughout the respiratory tract.
Conclusions:
- For nanometer-sized particles, non-phagocytic uptake mechanisms like macropinocytosis and electrokinetic phenomena may become significant.
- Translocation of nanoparticles into the interstitium and circulation allows interaction with other biological fluids and cell populations.
- Altered nanoparticle properties can influence their uptake and interaction with diverse lung macrophage populations, potentially involving previously underestimated cell types in particle clearance.

