title: Kinin generation in acute pneumonia and chronic bronchitis.
abstract: 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 lower airways. We studied bronchoalveolar lavage fluid (BALF) of patients with acute pneumonia, patients with chronic bronchitis and healthy controls. Kinins were determined by radioimmunoassay (RIA). Plasma kallikrein (pl-Kal), alpha2-macroglobulin (alpha2-M) and toluenesulphonylarginine methyl ester (TAME) esterase activity (TAME-ea) were studied in BALF before and after gel filtration chromatography. Plasma kallikrein and alpha2-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 with benzamidine, soy-bean-trypsin inhibitor (SBTI) and aprotinin was performed. Kinins and TAME-ea did not differ significantly between acute pneumonia and chronic bronchitis, whereas pl-Kal and alpha2-M values were significantly higher in acute pneumonia. Gel filtration revealed the highest TAME-ea peak in acute pneumonia corresponding with the first alpha2-M peak at approximately 800 kDa, whereas in chronic bronchitis the highest peak was found at approximately 40 kDa. The inhibition test showed that the TAME-ea peak at approximately 800 kDa was due to pl-Kal and the TAME-ea peak at approximately 40 kDa was mainly due to tissue kallikrein. High peaks of alpha2-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 plasma kallikrein whereas in chronic inflammation, kininogenases other than plasma kallikrein, such as tissue kallikrein, seem to be more important.
authors.affiliation: Dept of Clinical Immunology and Asthma, Virchow-Klinikum, Humboldt University Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.forename: B
authors.initials: B
authors.lastname: Peng
authors.forename: J
authors.initials: J
authors.lastname: Niehus
authors.forename: C R
authors.initials: CR
authors.lastname: Baumgarten
authors.forename: T
authors.initials: T
authors.lastname: Brunnée
authors.forename: S
authors.initials: S
authors.lastname: Thalhofer
authors.forename: P
authors.initials: P
authors.lastname: Dorow
authors.forename: G
authors.initials: G
authors.lastname: Kunkel
mesh_terms: D000208:Acute Disease; D000368:Aged; D001991:Bronchitis / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002850:Chromatography, Gel; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D007705:Kinins / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000378:metabolism; D011014:Pneumonia / Q000378:metabolism*; D011288:Prekallikrein / Q000378:metabolism; D011863:Radioimmunoassay; D012016:Reference Values; D000511:alpha-Macroglobulins / Q000378:metabolism
chemical_list: D007705:Kinins; D000511:alpha-Macroglobulins; D011288:Prekallikrein; D010447:Peptide Hydrolases; C023073:tosylarginine methyl ester hydrolase; D007610:Kallikreins