Role of IgE in hyperresponsiveness induced by passive sensitization of human airways.

Abstract

Incubation of airways from nonatopic patients with serum from patients with high IgE levels confers responsiveness to "specific" (allergen) and hyperresponsiveness to "nonspecific" (histamine) stimuli. We have tested the hypothesis that the level of IgE determines the degree of specific and nonspecific responsiveness. Bronchial rings from nonatopic patients were sensitized overnight with serum containing high levels of allergen-specific IgE, or with an allergen-specific chimeric IgE (JW8) in physiologic buffer. In vitro responsiveness to allergen and histamine was evaluated and compared with non-sensitized tissues from the same patients. Responses to specific allergen were demonstrated in all tissues sensitized with atopic serum or chimeric IgE, but not in nonsensitized tissues. Allergen responses were specific, since tissues sensitized using serum containing high Dermatohagoides farinae-specific IgE only, did not respond to either horse or dog allergens. The potency and magnitude of the maximal contraction to histamine was significantly (p < 0.05) increased in tissues sensitized using atopic serum with high total IgE concentrations compared with nonsensitized preparations, but was unchanged in tissues sensitized using chimeric IgE or serum with low total IgE levels. Therefore, specific IgE determines allergen responsiveness in passively sensitized human airways, but histamine hyperresponsiveness is independent of specific IgE and appears to be related to some other factor associated with serum containing high concentrations of total IgE.

Evaluation of the effects of the R- and S-enantiomers of salbutamol on equine isolated bronchi

“…Considering all these data, it is possible to hypothesize an analogous pro-inflammatory and pro-constrictory activity of S-salbutamol also in equine airways after only 90 min. of incubation,enhancing the potency of histamine, as has been demosntrated in human bronchi after passive sensitization [26].…”

Relaxant effect of brain natriuretic peptide in nonsensitized and passively sensitized isolated human bronchi

“…the incubation of isolated airways with IgE-rich serum obtained from atopic individuals, closely mimics features of bronchial hyperresponsiveness [22,33], a central abnormality in patients with asthma. It has been suggested that passive immune sensitization of human tissue confers an inherent change in the contractility of airway smooth muscle that may contribute to hyperresponsiveness, which could induce mast cell degranulation [33].…”

“…The sensitizing serum was prepared from the whole blood of patients suffering from atopic asthma (total IgE >250 u ml -1 , and specific IgE antibodies against common aeroallergens) during an exacerbation. Passive sensitization of human airway smooth muscle has been described previously [22]. Sera were not pooled but rozen at -80°C M A N U S C R I P T…”

Elevation of total serum immunoglobulin E is associated with asthma in nonallergic individuals

“…This concept is supported by several in vitro studies, which have shown that bronchial hyperresponsiveness in tracheal segments may occur after incubation with sera of patients with high IgE levels [33]. In this setting, it might be feasible to use monoclonal anti-IgE as asthma therapy even in nonallergic asthmatics.…”