KALLISTATIN, A NOVEL HUMAN TISSUE KALLIKREIN INHIBITOR - LEVELS IN BODY-FLUIDS, BLOOD-CELLS, AND TISSUES IN HEALTH AND DISEASE

Kallistatin, a human serine proteinase inhibitor, is a newly identifie d tissue kallikrein inhibitor. It binds strongly to tissue kallikrein but weakly to other serine proteinases such as chymotrypsin and elasta se. The tissue distribution and changes in kallistatin levels in human diseases were characterized by using specific monoclonal and polyclon al antibodies against kallistatin. Kallistatin antigen levels in blood cells, fluids, and tissues measured with a specific enzyme-linked imm unosorbent assay showed displacement curves that were parallel with th ose in purified kallistatin, indicating their immunologic identity. Ex pression of kallistatin mRNA in platelets, neutrophils, lymphocytes, m onocytes, endothelial cells, hepatocytes, and colon and prostate carci noma cells was identified by reverse transcription-polymerase chain re action followed by Southern blot analysis. Plasma kallistatin concentr ation was 22.1 +/- 3.5 mu g/ml in 30 normal subjects and 21.1 +/- 3.8 mu g/ml in 5 patients with C1 inhibitor deficiency, A significantly re duced kallistatin level (7.2 +/- 2.5 mu g/ml, p < 0.001) was seen in p lasma samples from 9 patients with liver disease and 10 patients with sepsis (7.7 +/- 3.5 mu g/ml, p < 0.001), Further, kallistatin levels i n 10 women taking oral contraceptives (19.8 +/- 3.8 mu g/ml) and 21 pr egnant women (14.9 +/- 3.3 mu g/ml) were significantly lower than thos e seen in healthy individuals. These data suggest that kallistatin is found in plasma, is produced mostly in the liver, and can be consumed during sepsis. Its consumption in sepsis may Indicate a protective rol e to prevent blood pressure lowering.