The novel rat kininogen, T-kininogen. A pro-inflammatory factor or a thiostatin?

Abstract

In Mammals, plasma contains at least two kininogens that are synthetized by the liver : high molecular weight kininogen (MW : about 110 000) and low molecular weight kininogen (MW : about 66 000). Both kininogens are composed by two polypeptide chains surrounding a nonapeptide, bradykinin. The heavy chain is similar for both kininogens while the light chain is distinct for each of them. In plasma, high molecular weight kininogen is present as complexes with coagulation factor XI and prekallikrein and it can stick to negatively charged surfaces by its histidine-rich light chain. High molecular weight kininogen is a cofactor for the triggering of the intrinsic pathway of blood coagulation. Schematically, the intrinsic pathway begins by the activation by negatively charged materials, of the Hageman factor or coagulation factor XII which, in turn, activates factor XI, plasminogen proactivator and prekallikrein. The activated kallikrein in presence of the high molecular weight kininogen accelerates the activation of Hageman factor and releases bradykinin from that kininogen. Several tissues, like exocrine glands, pancreas, salivary and sweat glands, or the kidneys contain tissue kallikreins that release kallidin or lysyl-bradykinin from both kininogens. Kinins are pro-inflammatory agents : they induce vasodilatation, pain, increase of vascular permeability and release prostaglandins from several types of cells. Prostaglandins most often increase the effects of kinins. Other proteases can also release kinins. The most often used of these proteases is trypsin that liberates bradykinin from both kininogens. Kinins are rapidly inactivated by kini-nase I and kininase II (review in Erdos, 1979).