Repeated antigen challenge induces airway hyperresponsiveness with tissue eosinophilia in guinea pigs

Abstract

To test the hypothesis that the development of airway hyperresponsiveness (AHR) lasting greater than or equal to 3 days after the last antigenic exposure required repeated mediator release, we compared dose-response changes in lung resistance (RL) to acetylcholine (ACh) in animals sensitized with 1% ovalbumin (OA), 4% Bordatella pertussis aerosol and subsequently challenged with 0.5% OA aerosol twice weekly for 4-6 wk vs. animals receiving saline aerosol instead of OA. Despite antihistamine pretreatment, each OA challenge produced cyanosis and inspiratory indrawing. Blood gas analysis in six guinea pigs revealed an immediate fall in arterial PO2 (PaO2) from 104.3 +/- 4.9 to 35.4 +/- 2.2 Torr after a 1-min exposure to aerosolized OA. ACh dose-response measurements of RL 3 days after the last OA challenge demonstrated a leftward shift and an increased magnitude of response. These differences were less marked at 7 days, and by 14 days after the last OA challenge, ACh dose-response curves were not different from those of control guinea pigs. Sensitization without repeated antigen challenge did not cause hyperresponsiveness. Morphometric analysis showed significantly increased numbers of eosinophils in the epithelium of airways in hyperresponsive guinea pigs, without neutrophil infiltration or alterations in epithelium and airway wall areas. We conclude that repeated antigenic challenge, but not sensitization alone, causes prolonged AHR in guinea pigs, which is associated with tissue eosinophilia.

Physiological responses of the airway wall and lung in hyperresponsive pigs

“…Responsiveness could be influenced by inflammatory stimulation and also by the presence of smooth muscle cells with different contractile or secretory phenotypes [17]. In some animal models, tracheal smooth muscle contraction is increased [1][2][3]. There are fewer studies in bronchi, but one human study showed decreased smooth muscle force in bronchi obtained post mortem [5].…”

“…Since smooth muscle contraction is a major determinant of airway diameter, one proposal has been that AHR is due to altered contractile behaviour of airway smooth muscle (ASM). Studies in allergic animal models indicate that ASM contraction might be increased [1][2][3], while the responses of smooth muscle isolated from asthmatics are variable [4,5]. In vivo, ASM is subject to additional factors arising from outside the airway, such as load from parenchymal tethering [6].…”

CpG-oligodeoxynucleotides inhibit RSV-enhanced allergic sensitisation in guinea pigs

“…Airway inflammation by T-cells and eosinophils is a feature of acute RSV infection in guinea pigs [9] and of human asthma [10]. OA-sensitised guinea pigs have increased airway eosinophils [6,8], but, to date, the current authors have not studied whether OA sensitisation of guinea pigs is associated with changes in airway T-cells. The combination of RSV infection and OA exposures is associated with the persistence of low levels of virus in the guinea pig lung [8], and, although RSV persistence is emerging as an area of considerable interest [11], it is unclear whether viral persistence contributes to the pathogenesis of RSV-enhanced allergic sensitisation.…”

“…The current authors have used guinea pigs as an animal model of experimental RSV bronchiolitis [5] and OA sensitisation [6], and have observed significantly higher titres of circulating OAspecific immunoglobulin (Ig)G 1 antibodies (the major class of Ig that mediates allergic responses in these guinea pigs [7]) in animals that had the combination of RSV infection and OA exposures, in comparison with OA exposures alone [8]. Airway inflammation by T-cells and eosinophils is a feature of acute RSV infection in guinea pigs [9] and of human asthma [10].…”

Avaliação da resposta inflamatória pulmonar e do transporte mucociliar em modelo de inflamação alérgica pulmonar: modulação pelo estresse induzido pela natação forçada

“…Rafael de Almeida dos Reis um infiltrado eosinofílico após sensibilização representam uma opção adequada para a utilização em modelos experimentais para estudo da resposta inflamatória alérgica (Kallós e Kallós, 1984;Dunn et al, 1988;Ishida et al, 1989).…”