Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1), also known as CD31, is a protein found on the surface of various cells within the circulatory system. It helps cells stick together and communicate. This protein plays a role in maintaining the health of blood vessels and supporting the immune system.
Structure and Location of PECAM-1
PECAM-1 is a transmembrane glycoprotein with a molecular weight around 130 kDa, which can vary based on its glycosylation. Its structure includes six immunoglobulin-like domains in its extracellular region, a transmembrane segment, and a cytoplasmic tail.
PECAM-1 is primarily found on the surface of endothelial cells, which form the inner lining of all blood vessels. PECAM-1 is also present on other cell types, including platelets, which are involved in blood clotting, and various immune cells such as monocytes, neutrophils, and some T-cells. This widespread distribution hints at its diverse functions throughout the body.
Physiological Roles of PECAM-1
PECAM-1 performs several functions that contribute to normal bodily processes, particularly within the vascular and immune systems. Its roles include maintaining the integrity of blood vessels, facilitating immune cell movement, and supporting the formation of new blood vessels.
Maintaining Vascular Integrity
PECAM-1 molecules located on the surface of adjacent endothelial cells bind to each other through homophilic interactions. This binding helps to create a tight, continuous barrier that lines blood vessels, preventing blood components from leaking into surrounding tissues. This continuous lining is similar to how interlocking tiles form a solid wall, ensuring the selective passage of fluids and substances and resisting mechanical forces from blood flow. PECAM-1 also functions as a mechanosensor, enabling endothelial cells to respond to fluid shear stress.
Transendothelial Migration (Diapedesis)
Transendothelial migration, also known as diapedesis, is the process by which immune cells exit the bloodstream and enter tissues to address infection or injury. PECAM-1 plays a significant role in this process by guiding immune cells, such as neutrophils and monocytes, through the junctions between endothelial cells. An immune cell uses PECAM-1 on its surface to interact with PECAM-1 on the endothelial cell, much like using a specific “handle” to pull itself through a “gate” in the vessel wall. This interaction helps the immune cell to squeeze between endothelial cells and pass through the vessel wall into the inflamed tissue.
Angiogenesis
Angiogenesis is the physiological process of forming new blood vessels from pre-existing ones. PECAM-1 contributes to this process, which is important during normal events like wound healing, tissue repair, and development. It is involved in the migration and organization of endothelial cells into new vascular tubes. Studies have shown that PECAM-1 participates in the adhesive and signaling events necessary for endothelial cells to move and then arrange themselves to form new blood vessels.
Involvement in Disease
While PECAM-1’s physiological roles are beneficial, these same functions can be altered or exploited in disease states. The protein’s involvement in processes like angiogenesis and immune cell migration can contribute to the progression of various illnesses when dysregulated. Understanding these dysfunctions provides insights into disease mechanisms.
Angiogenesis, the formation of new blood vessels, is a process tumors can exploit to sustain their growth and spread. Cancer cells induce the formation of new vessels to supply themselves with oxygen and nutrients, and PECAM-1 contributes to this pathological angiogenesis in human tumors. Antibodies targeting PECAM-1 have been shown to reduce the density of human vessels associated with tumors in experimental models. This suggests that PECAM-1 facilitates the motility and organization of endothelial cells that form the tumor’s blood supply.
The transendothelial migration of immune cells, while necessary for fighting infections, can contribute to chronic inflammation when it becomes overactive or misdirected. In conditions like atherosclerosis, which involves plaque buildup in arteries, PECAM-1 on endothelial cells can promote the infiltration of macrophages, contributing to lesion formation. Similarly, in rheumatoid arthritis, an autoimmune disease characterized by joint inflammation, inhibiting PECAM-1 has been shown to reduce inflammatory cell transmigration into the synovium, a tissue lining the joints. This highlights how the precise control of PECAM-1-mediated cell movement is important for preventing excessive inflammatory responses.
Clinical and Research Applications
Knowledge of PECAM-1’s functions has led to its application in clinical diagnostics and as a target in medical research. These practical uses leverage its specific cellular distribution and roles in health and disease. Continued investigation aims to refine these applications for patient benefit.
As a diagnostic marker, PECAM-1, identified as CD31, is widely used by pathologists. Because it is specifically expressed on endothelial cells, antibodies against CD31 are employed to stain tissue samples and identify the presence and density of blood vessels. This staining helps in assessing tumor angiogenesis, which can indicate a tumor’s aggressiveness and potential for metastasis. For instance, increased CD31 expression has been observed in certain cancers, correlating with new microvessel formation.
PECAM-1 is also being explored as a therapeutic target. Researchers are investigating strategies to block its function, particularly to inhibit tumor growth and reduce inflammation. For example, studies using anti-PECAM-1 antibodies have shown promise in suppressing tumor progression by affecting vessel formation or tumor cell proliferation. Similarly, inhibiting PECAM-1’s role in leukocyte migration could offer a way to manage chronic inflammatory conditions like atherosclerosis and rheumatoid arthritis by limiting immune cell infiltration. These approaches represent active areas of medical research aiming to develop new treatments.