The immune system constantly monitors for threats like pathogens and damaged cells. Blood transports immune cells throughout the body. To combat threats, these cells must leave the bloodstream and reach specific sites. This process begins with their interaction with the blood vessel wall.
What is Leukocyte Adhesion
Leukocyte adhesion is the process where leukocytes, or white blood cells, attach to the inner lining of blood vessels. This inner lining is called the endothelium, a single layer of cells forming the vessel wall. This attachment is a preliminary step, allowing these immune cells to begin their journey out of the bloodstream. Leukocytes identify and neutralize foreign invaders and cellular debris.
This adhesion differs from general blood flow, where cells move freely. It involves specific molecular interactions that cause leukocytes to slow down and stick. The endothelium becomes “sticky” in response to signals from surrounding tissues. This allows circulating leukocytes to recognize and bind to the vessel wall at precise locations.
The Purpose of Leukocyte Adhesion
Leukocyte adhesion is important for the body’s immune response, especially in inflammation and infection. It allows immune cells to exit the bloodstream at targeted sites. For instance, when tissue is injured or infected, chemical signals prompt local blood vessels to change. These changes facilitate leukocyte adhesion, allowing cells to concentrate at the problem site.
This targeted movement ensures immune cells, like neutrophils and macrophages, can reach areas to fight bacteria, viruses, or clear cellular debris. Without this adhesion, immune cells would remain largely confined to the circulatory system. This would limit their ability to defend against localized threats.
How Leukocytes Move Through Blood Vessels
The movement of leukocytes from the bloodstream into surrounding tissues is a multi-step process often termed “extravasation” or “diapedesis.” This sequence helps immune cells navigate from flowing blood to affected tissue. It begins with initial, transient interactions that slow the leukocyte.
Steps of Leukocyte Extravasation
Rolling: Leukocytes briefly interact with and “roll” along the endothelial surface. This weak attachment is mediated by selectins on both leukocyte and endothelial cell surfaces, slowing the leukocyte’s movement.
Activation: Triggered by chemical signals like chemokines from inflamed tissue, this activates both leukocyte and endothelial cells. Integrin molecules on the leukocyte surface switch to a high-affinity binding state.
Firm Adhesion: The leukocyte firmly attaches to the endothelium. Activated integrins on the leukocyte interact with adhesion molecules like ICAM-1 and VCAM-1 on endothelial cells. This strong attachment allows the leukocyte to withstand blood flow shear forces.
Transmigration: The leukocyte squeezes through gaps between endothelial cells to enter the underlying tissue. This involves cytoskeleton reorganization and interactions with proteins like PECAM-1. The leukocyte then penetrates the basement membrane.
Leukocyte Adhesion in Disease
When leukocyte adhesion is disrupted, it can lead to various disease states. Abnormal adhesion, whether excessive or deficient, can compromise the body’s health. This dysfunction can result in uncontrolled inflammation or a weakened immune response.
Excessive leukocyte adhesion can contribute to chronic inflammatory conditions. For instance, in autoimmune diseases like rheumatoid arthritis, increased expression of adhesion molecules such as ICAM-1 and VCAM-1 on endothelial cells promotes inflammatory cell infiltration into joints, perpetuating the disease. Similarly, in atherosclerosis, the hardening of arteries, heightened expression of E-selectin and P-selectin contributes to leukocyte recruitment to arterial walls, worsening plaque formation.
Conversely, impaired leukocyte adhesion can lead to immunodeficiency. Leukocyte adhesion deficiency (LAD) is a group of rare genetic disorders where leukocytes lack specific surface proteins. This prevents them from adhering to blood vessels and migrating to infection sites. This deficiency results in recurrent and often severe bacterial and fungal infections, poor wound healing, and a lack of pus formation. For example, LAD type I is caused by a defect in the CD18 protein, a component of integrins, preventing neutrophils from effectively leaving the bloodstream to fight pathogens in tissues.