TY - JOUR
T1 - Influx of kininogens into nasal secretions after antigen challenge of allergic individuals
AU - Baumgarten, C. R.
AU - Togias, A. G.
AU - Naclerio, R. M.
AU - Lichtenstein, L. M.
AU - Norman, P. S.
AU - Proud, D.
PY - 1985
Y1 - 1985
N2 - We have recently demonstrated that kinins are generated in vivo after nasal challenge with antigen of allergic, but not nonallergic, individuals. The present study was undertaken as a first step in determining the mechanism(s) of kinin formation during the allergic reaction and was directed towards establishing the availability and origin of kininogens in nasal secretions. Allergic individuals (n = 6) and nonallergic controls (n = 5) were challenged with antigen; and by using specific radioimmunoassays, nasal washes, obtained before and after challenge, were assayed for high molecular weight kininogen (HMWK), total kininogen (TK), albumin, and kinins. Dramatic increases in HMWK (1,730 ± 510 ng/ml), TK (3,810 ± 1035 ng/ml), kinin (9.46 ± 1.75 ng/ml), and albumin (0.85 ± 0.2 mg /ml) were observed after challenge of allergic individuals which correlated (P < 0.001) with increase in histamine and N-α-tosyl-L-arginine methyl esterase activity and with the onset of clinical symptoms. For nonallergic individuals, levels of kininogens, albumin, and all mediators after antigen challenge were not different from base line. Linear regression analysis revealed excellent correlations (P < 0.001 in each case) between increases in HMWK, TK, kinin, and albumin during antigen titration experiments and between the time courses of appearance and disappearance of HMWK, TK, kinin, and albumin after antigen challenge. Gel filtration revealed no evidence of degradation products of kininogens in nasal washes. For each allergic individual the ratio of HMWK/TK in postchallenge nasal washes was similar to the ratio of these two proteins in the same individual's plasma. These data suggest that, during the allergic reaction, there is an increase in vasular permeability and a transudation of kininogens from plasma into nasal secretions, where they can provide substrate for kinin-forming enzymes.
AB - We have recently demonstrated that kinins are generated in vivo after nasal challenge with antigen of allergic, but not nonallergic, individuals. The present study was undertaken as a first step in determining the mechanism(s) of kinin formation during the allergic reaction and was directed towards establishing the availability and origin of kininogens in nasal secretions. Allergic individuals (n = 6) and nonallergic controls (n = 5) were challenged with antigen; and by using specific radioimmunoassays, nasal washes, obtained before and after challenge, were assayed for high molecular weight kininogen (HMWK), total kininogen (TK), albumin, and kinins. Dramatic increases in HMWK (1,730 ± 510 ng/ml), TK (3,810 ± 1035 ng/ml), kinin (9.46 ± 1.75 ng/ml), and albumin (0.85 ± 0.2 mg /ml) were observed after challenge of allergic individuals which correlated (P < 0.001) with increase in histamine and N-α-tosyl-L-arginine methyl esterase activity and with the onset of clinical symptoms. For nonallergic individuals, levels of kininogens, albumin, and all mediators after antigen challenge were not different from base line. Linear regression analysis revealed excellent correlations (P < 0.001 in each case) between increases in HMWK, TK, kinin, and albumin during antigen titration experiments and between the time courses of appearance and disappearance of HMWK, TK, kinin, and albumin after antigen challenge. Gel filtration revealed no evidence of degradation products of kininogens in nasal washes. For each allergic individual the ratio of HMWK/TK in postchallenge nasal washes was similar to the ratio of these two proteins in the same individual's plasma. These data suggest that, during the allergic reaction, there is an increase in vasular permeability and a transudation of kininogens from plasma into nasal secretions, where they can provide substrate for kinin-forming enzymes.
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U2 - 10.1172/JCI111945
DO - 10.1172/JCI111945
M3 - Article
C2 - 4019778
AN - SCOPUS:0021965985
SN - 0021-9738
VL - 76
SP - 191
EP - 197
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 1
ER -