Plasma kallikrein

Plasma kallikrein is an enzyme that plays a crucial role in the human body's blood coagulation and inflammation processes. It is a serine protease that is primarily found in the blood plasma. Plasma kallikrein is involved in the activation of the kinin-kallikrein system, which is responsible for regulating blood pressure, inflammation, and pain.

Function

Plasma kallikrein is synthesized in the liver and released into the bloodstream. Once activated, it cleaves high molecular weight kininogen (HMWK) to produce bradykinin, a potent vasodilator and mediator of inflammation. Bradykinin acts by binding to specific receptors, leading to increased vascular permeability, smooth muscle contraction, and pain sensation.

Role in Blood Coagulation

Plasma kallikrein is an essential component of the intrinsic pathway of blood coagulation. It activates factor XII, also known as Hageman factor, which initiates a cascade of reactions leading to the formation of a blood clot. This pathway is important for maintaining hemostasis and preventing excessive bleeding.

Role in Inflammation

Plasma kallikrein is involved in the inflammatory response by generating bradykinin, which promotes vasodilation and increases vascular permeability. This allows immune cells and molecules to reach the site of injury or infection more easily. Additionally, bradykinin stimulates the release of other inflammatory mediators, such as prostaglandins and cytokines, further amplifying the inflammatory response.

Clinical Significance

Plasma kallikrein has been implicated in various pathological conditions. Excessive activation of the kinin-kallikrein system can lead to conditions such as hereditary angioedema (HAE), a rare genetic disorder characterized by recurrent episodes of swelling in various body parts. In HAE, mutations in the gene encoding plasma kallikrein or other components of the kinin-kallikrein system result in uncontrolled bradykinin production.

Inhibitors of plasma kallikrein have been developed as potential therapeutic agents for HAE and other inflammatory conditions. These inhibitors can prevent the excessive production of bradykinin, thereby reducing symptoms associated with inflammation and swelling.