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Updated: Aug 2, 2025
Isolation and In Vitro Culture of Murine and Human Alveolar Macrophages
Published on: April 20, 2018
A new tractable method for generating Human Alveolar Macrophage Like cells in vitro to study lung inflammatory
Susanta Pahari1, Eusondia Arnett1, Jan Simper1,2
1Host Pathogen Interactions and Population Health programs, Texas Biomedical Research Institute, San Antonio, TX, USA.
Abstract:
Alveolar macrophages (AMs) are unique lung resident cells that contact airborne pathogens and environmental particulates. The contribution of human AMs (HAM) to pulmonary diseases remains poorly understood due to difficulty in accessing them from human donors and their rapid phenotypic change during in vitro culture. Thus, there remains an unmet need for cost-effective methods for generating and/or differentiating primary cells into a HAM phenotype, particularly important for translational and clinical studies. We developed cell culture conditions that mimic the lung alveolar environment in humans using lung lipids, i.e. , Infasurf (calfactant, natural bovine surfactant) and lung-associated cytokines (GM-CSF, TGF-β, and IL-10) that facilitate the conversion of blood-obtained monocytes to an AM-Like (AML) phenotype and function in tissue culture. Similar to HAM, AML cells are particularly susceptible to both Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. This study reveals the importance of alveolar space components in the development and maintenance of HAM phenotype and function, and provides a readily accessible model to study HAM in infectious and inflammatory disease processes, as well as therapies and vaccines.
Importance:
Millions die annually from respiratory disorders. Lower respiratory track gas-exchanging alveoli maintain a precarious balance between fighting invaders and minimizing tissue damage. Key players herein are resident AMs. However, there are no easily accessible in vitro models of HAMs, presenting a huge scientific challenge. Here we present a novel model for generating AML cells based on differentiating blood monocytes in a defined lung component cocktail. This model is non-invasive, significantly less costly than performing a bronchoalveolar lavage, yields more AML cells than HAMs per donor and retains their phenotype in culture. We have applied this model to early studies of M. tuberculosis and SARS-CoV-2. This model will significantly advance respiratory biology research.
Insights
Researchers developed a new method to generate alveolar macrophage-like (AML) cells from blood monocytes. This cost-effective model mimics the lung environment, aiding research into respiratory diseases like tuberculosis and COVID-19.
Area of Science:
- Immunology
- Cell Biology
- Respiratory Medicine
Background:
- Alveolar macrophages (AMs) are crucial for lung immunity but difficult to study in humans.
- Existing methods for obtaining human AMs (HAMs) are invasive and cells change phenotype in culture.
- There is a need for accessible, cost-effective models of HAMs for research.
Approach:
- Developed a novel cell culture system mimicking the human lung alveolar environment.
- Used lung lipids (surfactant) and specific cytokines (GM-CSF, TGF-β, IL-10) to differentiate monocytes.
- Generated alveolar macrophage-like (AML) cells from blood monocytes.
Key Points:
- AML cells exhibit a phenotype and function similar to HAMs.
- AML cells are susceptible to infection by *Mycobacterium tuberculosis* and SARS-CoV-2.
- The model provides a readily accessible resource for studying lung diseases.
Conclusions:
- Alveolar space components are vital for HAM phenotype and function.
- This new AML model facilitates research into infectious and inflammatory lung diseases.
- The model supports studies on therapies and vaccines for respiratory conditions.
