Scientists concoct a 'magic cocktail' in lab to create lung’s critical immune cell
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Alveolar macrophages are important immune cells in the lungs that act in defense against pathogens and particulates humans inhale. Without these cells, the lungs would be immunocompromised and their sterility would be at risk. Alveolar macrophages, living in the lining of the lung’s air sacs, eat up the garbage in the tissues.
Mimicking the alveolar environment in cell culture, researchers at Texas Biomedical Research Institute have created the alveolar macrophage in a lab. The researchers claim this will help advance research into respiratory diseases, from diseases like COVID-19, tuberculosis and asthma, said the press release.
Respiratory disorders are a cause of death for millions of people. Alveolar macrophage plays a key role in fighting off these diseases and maintaining a balance between fighting invaders and minimizing tissue damage. “However, there are no easily accessible in vitro models of HAMs (human alveolar macrophages), presenting a huge scientific challenge,” noted the researchers. Human alveolar macrophages are hard to access as they reside deep in the lungs.
Typically collected through time-consuming and expensive lung washes, the team of researchers used a unique model that begins with a simple blood draw.
From the blood, the researchers separated the white blood cells and placed them in Teflon jars with specialized cell culture components. “Surfactant is added along with three different cytokine proteins, which are usually found in the alveolar lining fluid,” explained the researchers in a press release.
“We call it the magic cocktail,” says Susanta Pahari, a postdoctoral researcher and first author of the paper. “We are mimicking the alveolar environment in cell culture. It makes the cells think they are in the lungs.”
After six days, in this ‘magic cocktail,’ the cells either differentiate or transform into alveolar macrophage-like cells. The composition of these artificially generated cells is 94% genetically similar to human AMs. As the lab cells are able to perform the same function as a human AM, the team confirmed that the model can be used to investigate TB and COVID-19.
“It is very rewarding to develop something that can help the research community,” added Pahari. “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.”
Study abstract:
Alveolar macrophages (AMs) are unique lung resident cells that contact airborne pathogens and environmental particulates. The contribution of human AMs (HAMs) to pulmonary diseases remains poorly understood due to the 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, that is, Infasurf (calfactant, natural bovine surfactant) and lung-associated cytokines (granulocyte macrophage colony-stimulating factor, transforming growth factor-β, and interleukin 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.
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