Influx of kininogens into nasal secretions after antigen challenge of allergic individuals.

Abstract

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 increases in histamine and N-a-tosyl-Larginine 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 vascular permeability and a transudation of kininogens from plasma into nasal secretions, where they can provide substrate for kinin-forming enzymes.

Pathophysiology of Allergic Rhinitis

“…The exudation process is a noninjurious, ful ly reversible process of almost unfiltered bulk blood flow of different-sized proteins [55]. The plasma exudate provides a wide range of inflammatory enzymes including kinins [56][57][58][59][60], vascular-derived mediators including albumin [61], im munoglobulins, plasma-derived histamine and proinflamniatory mediators and activated complement fractions [62] …”

Formoterol and salbutamol inhibit bradykinin‐ and histamine‐induced airway microvascular leakage in guinea‐pig

“…Asthmatic patients have elevated kinin concentrations in plasma (Abe et al, 1967) and in nasal and bronchoalveolar lavage fluid after antigen challenge (Baumgarten et al, 1985;Christiansen et al, 1987). Both intravenous and inhaled bradykinin cause bronchoconstriction in asthmatic, but not in normal subjects (Simonsson et al, 1973;Newball et al, 1975;Fuller et al, 1987;).…”

Role of Endothelial Cells in Inflammatory Processes

“…Second, the activation of glandular kallikrein leads to a kinin generation promoting the inflammatory cascade, e.g. by liberating tachykinins and platelet-activa ting factor [3][4][5][6], Third, kinins arc strong vasodilators by inducing the release of nitric oxide and prostacyclin from endothelial cells [18,19]. In summary, we could demon strate a kallikrein activity in human and bovine endo thelial cells by immunostaining, by demonstrating kinin generation in cell homogenates and by an enzymatic as say, measuring glandular kallikrein activity.…”

“…bronchial and nasal lavage fluid in allergic and infectious diseases [1][2][3][4]. In flammatory mediators mediate and promote adhesion of granulocytes and lymphocytes to endothelial cells, leak age of vascular endothelium followed by an exsudation of plasma and migration of granulocytes and lymphocytes through the vascular wall.…”