Study Investigates the Role of Macrophages in Pulmonary Fibrosis Development

The role macrophages play in the development of pulmonary fibrosis, which impacts as many as 100,000 U.S. citizens a year, has always been something of a mystery.

Researchers at the University of Buffalo are exploring new paths to study pulmonary fibrosis and advancements that could ultimately lead to more effective medicine and therapies for the disease.

“For many years, our laboratory has focused its research efforts on pulmonary fibrosis, particularly interested in understanding the mechanisms behind its formation,” says study author Ruogang Zhao, associate professor of biomedical engineering at the University at Buffalo. “Immune cells, notably macrophages, have long been suspected to play a critical role in the development of pulmonary fibrosis, but their exact function remains elusive.”

Recent studies have revealed the presence of specific macrophage subtypes in various lung diseases, such as COPD, lung cancer, and pulmonary fibrosis.

“These discoveries indicate that different diseases may involve distinct macrophage populations,” Zhao says. “Our current research aims to delineate the roles these specific macrophage subtypes play in the development of pulmonary fibrosis.”

As part of the study, the research team developed miniature models of fibrotic lung tissues that acted as a proxy for someone with pulmonary fibrosis.

“Our research employs a novel miniature model that incorporates macrophages, lung fibroblasts, and collagen fibers in a co-culture system,” Zhao says. “This setup enables direct observation of the interactions among these components, providing insights into how macrophages contribute to fibrosis formation and respond to anti-fibrosis treatments.”

The study’s findings suggest that a particular population of macrophages in fibrotic lung tissue is sensitive to changes in the mechanical properties of their environment, such as increased tissue stiffness and the reorganization of collagen fibers.

“These conditions are commonly observed in fibrotic lungs,” Zhao says. “We have demonstrated that this hypersensitivity to mechanical changes prompts these macrophages to secrete growth factors, thereby contributing to the progression of pulmonary fibrosis. Moreover, we have identified that targeting the mechanical sensitivity of these macrophages with anti-fibrosis drugs can inhibit their pro-fibrotic activities.”

This new model serves as a versatile platform technology, facilitating the study of disease mechanisms in pulmonary fibrosis and the evaluation of new anti-fibrosis drugs’ efficacy.

“The model’s ability to display direct interactions between macrophages and fibroblasts underscores its potential as a powerful tool in investigating the interplay between immune and stromal cells,” Zhao says. “This interaction is crucial not only in fibrotic diseases but also in other lung conditions like COPD and lung cancer.”

By unveiling previously unknown mechanisms of action for FDA-approved anti-fibrosis drugs, the model has also proven instrumental in advancing drug discovery and development in this field.

“We anticipate that the widespread adoption of this model will significantly accelerate future anti-fibrosis drug discoveries,” Zhao says.