Activation

The key agent triggering kinin production is factor XIIa, activated Hageman factor. This converts plasma or tissue prekallikrein, an inactive precursor, into kallikrein. Kallikrein is an enzyme which acts on kininogens, another group of plasma inactive precursor proteins. Kallikrein co-incidentally exhibits chemotactic activity for leukocytes. Kallikreins activate, and kininogens are co-factors in the production of, factor XIIa, so supporting amplification circuits.

Kininogens are cleaved into different kinin products depending on the source of kallikrein or homologous enzyme:

• tissue kallikreins in exocrine glands such as the pancreas and salivary glands generate a decapeptide termed kallidin
• plasma kallikrein produces a nonapeptide termed bradykinin
• mast cells and basophils release a serine protease with similar activity to kallikrein
• activated complement factor C2 has a kinin-type activity

All the elements forming bradykinin leak out of vessels at the site of inflammation, so localising the response to the site in which factor XII encounters damaged tissue e.g. exposed collagen.