**Pathophysiology of Bradykinin-Mediated Angioedema: The Role of the Complement System**

Jesús Jurado‐Palomo and Teresa Caballero

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/67704

#### **Abstract**

The "complement system" is one of the effector pathways of the immune system against microorganisms and tumor cells. The complement system can be activated through three major pathways: classical, lectin, and alternative. The sequential activation through the generation of complex enzymes from inactive zymogens produces a cascade in which a capable enzyme generates a large number of active downstream molecules.

C1 inhibitor (C1‐INH) is a serine protease inhibitor (serpin) that regulates the following closely interrelated proteolytic pathways: complement system, coagulation system, contact system, and fibrinolysis system. The absence or malfunction of C1‐INH results in the presence of attacks of angioedema (AE) due to uncontrolled activation of the con‐ tact system, with the generation of bradykinin (BK), a vasoactive peptide released from high‐molecular‐weight kininogen (HMWK). Some drugs that inhibit the catabolism of BK have been implicated in the development of AE. These include angiotensin‐converting enzyme inhibitors (ACEIs), dipeptidyl peptidase IV (DPP‐IV) inhibitors, aminopeptidase P (APP) inhibitors, and neutral endopeptidase (NEP) inhibitors.

We describe in this chapter the biochemistry pathways implicated in the pathophysiology of bradykininergic angioedema (BK‐AE) and the role of the complement system in the prototype of BK‐AE, in hereditary angioedema with C1‐INH deficiency (C1‐INH‐HAE), and also in acquired angioedema with C1‐INH deficiency (C1‐INH‐AAE).

**Keywords:** acquired angioedema, aminopeptidase P, angioedema, angiotensin‐ converting enzyme, bradykinin, C1 inhibitor, carboxypeptidase, complement system, contact system, dipeptidyl peptidase‐IV, endothelin‐converting enzyme‐1, factor XII, fibrinolysis system, hereditary angioedema, neutral endopeptidase

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