Researchers at Texas Biomedical Research Institute successfully generated alveolar macrophages, the lung’s specialized immune cells, in a laboratory setting. This development offers an affordable and accessible cell culture model, advancing the study of lung inflammatory diseases. These findings were published in the journal mBio.
Alveolar macrophages, residing in the lining of the lung’s air sacs where crucial air exchange occurs, are typically the first immune cells to encounter pathogens like SARS-CoV-2 or tuberculosis-causing bacteria entering the deep lungs.
Studying human alveolar macrophages has proven challenging due to their location deep within the lungs and limited accessibility. The current method involves laborious and expensive lung washes, requiring the use of a bronchoscope to collect fluid samples from the airways.
However, the model developed at Texas Biomed begins with a simple blood draw, isolating white blood cells, which are then placed in Teflon jars with specialized cell culture components. By adding surfactant and three key cytokine proteins found in the alveolar lining fluid, the researchers successfully recreated the alveolar environment in cell culture.
In less than a week, the isolated cells differentiate into alveolar macrophage-like cells with a 94% genetic similarity to human alveolar macrophages collected through the conventional lung wash method. The scientists further validated their model by demonstrating that these generated cells efficiently engulf and neutralize pathogens such as tuberculosis and SARS-CoV-2, making them valuable tools for investigating lung infections and evaluating potential therapies.
Dr. Susanta Pahari, the paper’s first author and a postdoctoral researcher at Texas Biomed, explains, “It is very rewarding to develop something that can help the research community. We’ve already received numerous emails across the globe requesting macrophage development protocols. We are now looking into developing a kit that we can provide to make it even easier for others to replicate what we have done.”
During the COVID-19 pandemic, Dr. Pahari faced difficulty accessing human alveolar macrophages, prompting him to shift his focus towards developing an alternative method. After years of trial and error, the researchers identified the most effective combination of components, closely resembling the process used to generate adult induced pluripotent stem cells.
Dr. Larry Schlesinger, the senior author of the study, expressed excitement regarding the potential of these alveolar macrophage-like cells, envisioning their integration into next-generation lung organoids. Overall, these findings show promise to advance our understanding of lung inflammatory diseases and facilitate the development of novel therapeutic strategies.