Plasma kallikrein during experimentally induced allergic rhinitis: role in kinin formation and contribution to TAME-esterase activity in nasal secretions.
We have shown recently that kinins are generated during experimentally induced allergic rhinitis in man, and have demonstrated that substrates for kinin-forming enzymes are provided during the allergic response by a transudation of kininogens from plasma into nasal secretions. In light of this increased vascular permeability during the allergic reaction, we have extended our studies on the mechanisms of kinin formation to examine the potential involvement of plasma kallikrein. Allergic individuals (n = 7) and nonallergic controls (n = 7) were challenged intranasally with an allergen, and nasal lavages, obtained before and after challenge, were assayed for immunoreactive human plasma kallikrein/prekallikrein (iHPK). Post-challenge iHPK values were significantly elevated (p less than 0.01) in the allergic group (353 +/- 394 ng/ml; x +/- SD) as compared to the nonallergics (19 +/- 22 ng/ml), and correlated with increases in kinins, histamine, and N-alpha-tosyl-L-arginine methyl esterase (TAME-esterase) activity and with the onset of clinical symptoms. Gel filtration studies revealed that plasma prekallikrein is activated during the allergic response and contributes to kinin formation prior to interaction with plasma protease inhibitors. We also show that the majority of the TAME-esterase activity detected in nasal secretions during the allergic response is due to activities consistent with a plasma kallikrein/alpha 2-macroglobulin complex and with mast cell tryptase.
D000293:Adolescent; D000328:Adult; D002850:Chromatography, Gel; D006801:Humans; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000097:blood* / Q000502:physiology; D007704:Kininogens / Q000302:isolation & purification; D007705:Kinins / Q000096:biosynthesis*; D008875:Middle Aged; D008970:Molecular Weight; D009297:Nasal Mucosa / Q000201:enzymology* / Q000378:metabolism; D009299:Nasal Provocation Tests; D010447:Peptide Hydrolases / Q000378:metabolism*; D006255:Rhinitis, Allergic, Seasonal / Q000097:blood* / Q000201:enzymology
D007704:Kininogens; D007705:Kinins; D010447:Peptide Hydrolases; C023073:tosylarginine methyl ester hydrolase; D007610:Kallikreins