Natural Anticoagulant Protected Mice from Severe Lung Fibrosis

Mice that produce excessive amounts of an anticoagulant factor are somewhat protected against pulmonary fibrosis development, a finding that highlights the possibility of manipulating natural anti-clotting proteins in the fight against lung fibrosis.

Experiments showed that high levels of the anticoagulant protein C caused fewer macrophage inflammatory cells to move into the lungs, demonstrating the connection between blood clotting and immune processes in lung fibrosis.

The study, “High endogenous activated protein C levels attenuates bleomycin-induced pulmonary fibrosis,” appeared in the Journal of Cellular and Molecular Medicine.

Scientists know that patients with idiopathic pulmonary fibrosis (IPF) have abnormal blood-clotting responses, contributing to the development of lung fibrosis. But while the activation of coagulation is well-studied, researchers at the Academic Medical Center in the Netherlands noted that the role of natural anticoagulants is less clear.

The research team used a mice model, genetically engineered to produce high levels of the anticoagulant protein C. They exposed the mice to bleomycin — a chemical that triggers the development of lung fibrosis — and investigated how fibrosis developed.

Comparing the development to that of normal mice, the research team did not note any differences during the first two weeks. Taking another look after 28 days, however, the team noted that in normal mice treated with bleomycin the fibrosis had worsened.

In contrast, mice with high anticoagulant levels did not get worse after the first two weeks. They also had lower levels of the fibrotic factor TGF-beta than normal mice.

Since the migration of macrophages into the lungs is a key event in developing fibrosis, researchers measured the numbers of the inflammatory cells in the lungs of both types of mice. Mice with high anticoagulant levels had lower numbers of macrophages in their lungs, and lab tests showed the anticoagulant protein prevented the migration capacity of the cells.

The coagulation factor thrombin is known to promote fibrosis development by triggering fibroblasts. Higher levels of the anticoagulant protein C did not, however, prevent thrombin’s actions on fibroblast cells, which contribute to lung fibrosis by the production of excessive amounts of the collagen-rich meshwork known as extracellular matrix.

The data support a possibility that improving the levels of anti-clotting factors in patients may be beneficial, particularly if such treatments are used together with therapies acting on other fibrotic processes.