The circulatory system relies on a specialized lining of cells, known as endothelial cells, to function correctly. These cells form a single-cell layer that separates the blood from the surrounding tissues. Their health dictates the health of the entire vascular system, influencing blood pressure regulation and tissue oxygenation. Identifying and studying these cells is fundamental to vascular biology, and this is where the protein CD31 comes into focus. CD31 serves as a widely recognized marker, providing researchers and clinicians with a molecular fingerprint for this cell population.
Defining the Endothelial Cell and CD31
Endothelial cells are specialized squamous cells that coat the inside of all blood and lymphatic vessels, from the largest arteries to the smallest capillaries. This layer acts as an interface between the flowing blood and the vessel wall. The cell surface is decorated with many proteins, one of the most prominent being CD31, also known as Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1).
CD31 is a transmembrane glycoprotein belonging to the immunoglobulin gene superfamily. It is heavily concentrated at the junctions where endothelial cells meet, acting as a molecular seal and a signaling hub. In research settings, CD31 expression is used to positively identify and quantify endothelial cells. While CD31 is also expressed on other cell types, including platelets and various leukocytes, its high concentration and specific localization at the endothelial cell-cell border make it the definitive marker for the vascular lining.
Regulating the Vascular Barrier
The primary function of CD31 endothelial cells is the maintenance of the vascular barrier, which controls the passage of fluids, solutes, and proteins. CD31 molecules engage in homophilic interactions, meaning the CD31 on one cell binds to a CD31 molecule on an adjacent cell, directly contributing to the structural integrity of the tight junction. This physical connection is paramount to keeping the vessel sealed and preventing leakage into surrounding tissues.
The barrier function is also regulated by CD31’s role as a mechanosensor, allowing the endothelium to respond to the physical force of blood flow, known as fluid shear stress. Signaling pathways initiated by CD31 help the cells adapt to mechanical forces, which is necessary for long-term vascular stability. CD31 signaling is also involved in restoring the vessel barrier after it has been breached by inflammatory challenges. Its cytoplasmic tail contains signaling motifs that recruit intracellular phosphatases, such as SHP-2, which modulate junctional proteins to re-establish a sealed barrier.
Building and Maintaining Blood Vessels
CD31 endothelial cells are dynamically involved in the growth and remodeling of the vascular network. This includes angiogenesis, the process where new blood vessels sprout from pre-existing ones, necessary for tissue growth and repair after injury. During this process, CD31 is crucial for facilitating the migration and alignment of endothelial cells as they form a new hollow tube structure.
Inhibition of CD31 function has been shown to block the formation of new vascular tubes in laboratory models, demonstrating its direct involvement in the physical organization of the vessel wall. CD31 also marks a population of circulating endothelial progenitor cells (EPCs) mobilized from the bone marrow. These EPCs migrate to sites of injury to contribute to vasculogenesis, the de novo formation of blood vessels. This capacity for growth and repair highlights the dynamic nature of CD31-positive cells in response to tissue demand.
Involvement in Immunity and Illness
CD31 endothelial cells play a dual role in the immune system, both facilitating the immune response and protecting the vessel itself. During inflammation, CD31 is a necessary component for leukocyte transmigration, the process where immune cells like T-cells and neutrophils pass through the endothelial layer to reach infected or damaged tissue. The homophilic interaction of CD31 on the endothelial cell with CD31 on the immune cell guides the leukocyte through the cell-cell junction.
CD31 signaling protects the endothelium from damage during this intense immune activity. It helps confer an “immune privilege” to the vascular lining by preventing endothelial cell death that could be triggered by inflammatory signals. Downstream signaling activates anti-apoptotic pathways, preserving the vessel’s structural integrity even as immune cells pass through. Dysfunction of these cells is implicated in major illnesses, including cardiovascular disease, where loss of CD31-mediated stability contributes to conditions like atherosclerosis. Furthermore, the ability of CD31 endothelial cells to drive new vessel growth is hijacked in cancer, where uncontrolled tumor angiogenesis provides a blood supply for malignant tumors, making CD31 a potential target for therapeutic intervention.