An international team of researchers have discovered that a distinctive group of white blood cells help maintain the balance of collagen deposition in blood vessels and prevent vascular diseases.
Macrophages form a crucial part of the immune system. They are known to destroy pathogenic or foreign cells that enter the body, but scientists have recently discovered that certain macrophage sub-groups play more diverse roles than previously thought.
“Advanced technologies are helping us identify specialized groups of macrophages resident in specific parts of the body,” says Florent Ginhoux, at A*STAR’s Singapore Immunology Network, one of the scientists who worked on the project led by Véronique Angeli from the National University of Singapore. “We explored a hypothesis that arterial-resident macrophages contribute to vascular integrity, potentially influencing the development of vascular diseases.”
In a healthy circulatory system, arteries transport oxygenated blood, nutrients and cells, and help maintain organs and tissues. Arteries are composed of three layers; an inner membrane, a central media comprising smooth muscle cells and elasticated sheets, and an outer layer of connective tissues including collagen and elastin. Disrupting the balance between the production and degradation of collagen and the maintenance of elastin in arterial walls affects their mechanical function, leading to hardening (or ‘arterial stiffness’) and subsequent vascular deterioration.
In a series of experiments on mouse aortas, the researchers showed that macrophages found in the outer arterial walls are crucial for regulating collagen production and deposition. This specialized macrophage population expresses a protein receptor, LYVE-1, for hyaluronic acid — a molecule that plays a role in cell proliferation and migration. By expressing LYVE-1, the macrophages interact with hyaluronic acid in the smooth muscle cells found in the arterial walls. They then work together to regulate and degrade collagen.
The team generated a mouse model with depleted LYVE-1+ macrophages. Within weeks, the walls of the mice arteries had thickened, with reduced elasticity and limited vessel dilation.
“Arterial LYVE-1+ macrophages are present throughout human tissues, too. This is exciting because we may be able to develop drugs that target and boost the activity of these cells to treat disease,” says Ginhoux. “But I would urge caution. We will need to make sure that other therapies, like those used to deplete macrophages associated with cancerous tumors for example, do not kill this or other key macrophage communities by mistake.”
Ginhoux’s lab are now investigating how macrophages help control the permeability of blood vessel walls. “These cells act like gatekeepers, in many senses,” notes Ginhoux.
Lim, H. Y., Lim, S. Y., Tan, C. K., Thiam, C. H., Goh, C. C. et al. Hyaluronan receptor LYVE-1-expressing macrophages maintain arterial tone through hyaluronan-mediated regulation of smooth muscle cell collagen. Immunity 49, 1-16 (2018). | Article