Possible Mechanisms of Airway Hyperresponsiveness after Late Asthmatic Response in Guinea Pigs

Abstract

To elucidate the mechanism of airway hyperresponsiveness after late asthmatic response (LAR), we analyzed bronchoalveolar lavage fluid (BALF) and examined the airway smooth muscle contractility to acetylcholine (ACh). On day 1 after LAR, there was a significant positive correlation between the number of neutrophils in BALF and the increase in airway responsiveness after LAR (r = 0.82, p < 0.01). In the in vitro study, the dose response curve to ACh was significantly shifted to the left after removal of the epithelium in control guinea pigs. However, in hyperresponsive animals after LAR, removal of the epithelium had no significant effect on ACh-induced response. These results indicate that infiltration of neutrophils and other inflammatory cells induce epithelial damage and hence the development of airway hyperresponsiveness after LAR.

Repeated Antigen Inhalation-Induced Reproducible Early and Late Asthma in Guinea Pigs.

“…On the other hand, it is not known why LAR was hardly observed at any time of the challenge in the group sensitized/challenged with OA alone, even though several reports have indicated that LAR occurs at the challenge following 1 to 3 times sensitization with antigen for a relatively short period of time (12)(13)(14)(15)(16). In contrast, it is interesting that the LAR was elicited by repeated sensitizations/challenges with OA + Al(OH)3/OA, although serum levels of Ti and IgE were quite high in either sensitization/challenge method (Groups 2 and 4).…”

“…For the last decade, among diverse studies in experimental bronchial asthma using guinea pigs, many researchers have extensively focused on the early asthmatic response (EAR) and late asthmatic response (LAR), especially in relation to pulmonary hyperresponsiveness and eosinophil accumulation. Irrespective of sensitization by injection or aerosol inhalation of antigen, most reports have indicated that first, second or thir challenge with antigen by inhalation induces not only EAR but also LAR (12)(13)(14)(15)(16).…”

The Regulation of Pulmonary Immunity

“…Using this method of sensitization, guinea pigs exhibit strain differences in blood eosoniphilia and bronchial hyperreactivity (Winthereik et al, 1992). Increased responsiveness to acetylcholine after antigen challenge and late-phase bronchoconstriction correlates with BAL neutrophilia (Asano et al, 1994). This method of immunization is very different from that which occurs in humans, and the pulmonary physiologic response of guinea pigs is dissimilar to human asthma.…”

Intratracheal Sensitization/Challenge-Induced Biphasic Asthmatic Response and Airway Hyperresponsiveness in Guinea Pigs

“…In addition, when sensitized guinea pigs are exposed to an aerosolized antigen, a characteristic feature of chronic asthma known as the late asthmatic response (LAR) is evoked several hours after an early asthmatic response (EAR) that occurs approximately 10 min after the challenge. [8][9][10][11][12] We too have developed an animal model of asthma showing a LAR, in which guinea pigs were sensitized and challenged through exposure to aerosolized ovalbumin (OVA)ϩ Al(OH) 3 and OVA alone, respectively.…”