Kinins are generated in vivo following nasal airway challenge of allergic individuals with allergen.
Using a recently developed model of nasal challenge, we have obtained data that clearly demonstrate, for the first time, kinin generation during a local allergic reaction in vivo. Allergic individuals (n = 8) and matched nonallergic controls (n = 8) were challenged intranasally with the appropriate antigen and nasal washes were taken before and after challenge. Washes were assayed for kinin, histamine, and [3H]-N-alpha-tosyl-L-arginine methyl ester (TAME)-esterase activity. Increased kinin generation was found by radioimmunoassay (RIA) in the nasal washes of all the allergics (5,560 +/- 1,670 pg/ml) but in none of the controls (38 +/- 16 pg/ml). The presence of kinin was highly correlated with that of histamine and TAME-esterase activity and with the onset of clinical symptoms (P less than 0.001). Serial dilutions of nasal washes produced RIA displacement curves that paralleled the standard curve, and recovery of standard kinins that were added to nasal washes was 100 +/- 4% (n = 14). Kinin recovery was identical in both allergics and controls and did not vary significantly with antigen challenge. The immunoreactive kinin in nasal washes was stable to boiling and not precipitated by ethanol, but completely destroyed by carboxypeptidase B. It was evenly distributed between the sol and gel phases of nasal washes. High performance liquid chromatography analysis of the immunoreactive kinin in nasal washes showed it to be a mixture of lysylbradykinin and bradykinin. We conclude that kinins are produced during local allergic reactions in the nose and may contribute to the symptomatology of the allergic response.
D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006632:Histamine / Q000096:biosynthesis; D006801:Humans; D007705:Kinins / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism; D010447:Peptide Hydrolases / Q000096:biosynthesis; D006255:Rhinitis, Allergic, Seasonal / Q000378:metabolism*
D000485:Allergens; D007705:Kinins; D006632:Histamine; D010447:Peptide Hydrolases; C023073:tosylarginine methyl ester hydrolase