KININ GENERATION IN ACUTE PNEUMONIA AND CHRONIC-BRONCHITIS

Kinins are potent inflammatory mediators, liberated from kininogens by different kininogenases. The aim of this study was to investigate the kinin generation pathways in acute and chronic inflammation of the lo wer airways. We studied bronchoalveolar lavage fluid (BALF) of patient s with acute pneumonia, patients with chronic bronchitis and healthy c ontrols. Kinins were determined by radioimmunoassay (RIA). Plasma kall ikrein (pl-Kal), alpha(2)-macroglobulin (alpha(2)-M) and toluenesulpho nylarginine methyl ester (TAME) esterase activity (TAME-ea) were studi ed in BALF before and after gel filtration chromatography. Plasma kall ikrein and alpha(2)-M were measured using two newly developed sandwich enzyme-linked immunosorbent assays (ELISAs). TAME-ea was measured by a radiochemical assay. After gel filtration, inhibition of TAME-ea wit h benzamidine, soy-bean-trypsin inhibitor (SBTI) and aprotinin was per formed. Kinins and TAME-ea did not differ significantly between acute pneumonia and chronic bronchitis, whereas pl-Kal and alpha(2)-M values were significantly higher in acute pneumonia. Gel filtration revealed the highest TAME-ea peak in acute pneumonia corresponding with the fi rst alpha(2)-M peak at similar to 800 kDa, whereas in chronic bronchit is the highest peak was found at similar to 40 kDa. The inhibition tes t showed that the TAME-ea peak at similar to 800 kDa was due to pl-Kal and the TAME-ea peak at similar to 40 kDa was mainly due to tissue ka llikrein. High peaks of alpha(2)-M and pl-Kal were found in pneumonia and only small peaks were seen in chronic bronchitis. We conclude that in acute airway inflammation kinins seem to be mainly generated by pl asma kallikrein whereas in chronic inflammation, kininogenases other t han plasma kallikrein, such as tissue kallikrein, seem to be more impo rtant.