Pathways for bradykinin formation and inflammatory disease.
Bradykinin is formed by the interaction of factor XII, prekallikrein, and high-molecular-weight kininogen on negatively charged inorganic surfaces (silicates, urate, and pyrophosphate) or macromolecular organic surfaces (heparin, other mucopolysaccharides, and sulfatides) or on assembly along the surface of cells. Catalysis along the cell surface requires zinc-dependent binding of factor XII and high-molecular-weight kininogen to proteins, such as the receptor for the globular heads of the C1q subcomponent of complement, cytokeratin 1, and urokinase plasminogen activator receptor. These 3 proteins complex together within the cell membrane, and initiation depends on autoactivation of factor XII on binding to gC1qR (the receptor for the globular heads of the C1q subcomponent of complement). There is also a factor XII-independent bypass mechanism requiring a cell-derived cofactor or protease that activates prekallikrein. Bradykinin is degraded by carboxypeptidase N and angiotensin-converting enzyme. Angioedema that is bradykinin dependent results from hereditary or acquired C1 inhibitor deficiencies or use of angiotensin-converting enzyme inhibitors to treat hypertension, heart failure, diabetes, or scleroderma. The role for bradykinin in allergic rhinitis, asthma, and anaphylaxis is to contribute to tissue hyperresponsiveness, local inflammation, and hypotension. Activation of the plasma cascade occurs as a result of heparin release and endothelial-cell activation and as a secondary event caused by other pathways of inflammation.
Kaplan
Allen P
AP
Department of Medicine, Medical University of South Carolina, 29425, USA.
Joseph
Kusumam
K
Silverberg
Michael
M
D000707:Anaphylaxis / Q000503:physiopathology; D000799:Angioedema / Q000503:physiopathology; D001249:Asthma / Q000503:physiopathology; D001920:Bradykinin / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D012221:Rhinitis, Allergic, Perennial / Q000503:physiopathology
D001920:Bradykinin