Li-Jing Xu

The relationship between late asthmatic responses and antigen-specific immunoglobulin

The aim of this study was to examine the relationships between allergen-induced early and late airway responses and antigen-specific IgE, IgG, and lymphocyte subsets in blood and bronchoalveolar lavage (BAL). Brown Norway rats were sensitized at 7 weeks of age with ovalbumin (1 mg s.c.) with use of Bordetella pertussis as an adjuvant. Three weeks after sensitization, animals were anesthetized and challenged with an aerosol of ovalbumin (5% wt/vol in saline) for 5 minutes. Each animal was studied for 8 hours with repeated measurements of lung resistance. Blood was obtained at 0, 1, 2, and 3 weeks before ovalbumin challenge. Ovalbumin-specific IgE and IgG were determined by ELISA. No specific antibody was detectable before sensitization. Ovalbumin-specific IgE and IgG rose between 1 to 2 weeks after sensitization and peaked at 3 weeks. The IgE level did not correlate with the magnitude of either the early or the late responses. In a similar manner no correlation existed between the magnitude of specific IgG and the late response. However, a significant inverse correlation (r = -0.73; p < 0.01) occurred between specific IgG and the early response. No correlation occurred between the ratio of helper (W3/25 +) to suppressor (OX-8 +) lymphocytes in blood and BAL and airway responses to allergen. The size of the early and late responses were correlated, suggesting a common stimulus. Despite the blunting of the early response by repeated sensitization the late response was unaffected, suggesting that the factors that determine the physiologic expression of the early and late responses are different.

Depletion of CD8+ T cells enhances pulmonary inflammation but not airway responsiveness after antigen challenge in rats

BACKGROUND CD8+ (OX-8+) T cells may suppress airway inflammation and airway responsiveness after allergen challenge. OBJECTIVE We studied the effects of depletion of OX-8+ T cells on allergen-induced lung eosinophilia and airway responsiveness in the Sprague-Dawley rat. METHODS Sprague-Dawley rats were sensitized to ovalbumin and challenged by aerosol 14 days later. Test animals received either low-dose (2 mg, n = 9) or high-dose (3 mg, n = 7) OX-8 monoclonal antibody (mAb), whereas controls (n = 8) received BALB/c ascites fluid. A fourth group of animals (n = 10) was not sensitized to ovalbumin and also received ascites fluid. Twenty-four hours after ovalbumin challenge, responsiveness to methacholine was measured, and lung inflammation was assessed in the large airways and small airways and parenchyma. RESULTS Circulating and airway CD8+ T cells were decreased by OX-8 mAb administration with greatest changes in animals treated with high-dose OX-8 mAb compared with controls (blood: 1.0% +/- 3.6% vs 18.7% +/- 3.9%, p < 0.05); (large airways: 2.5% +/- 1.2% vs 13.8% +/- 1.2%, p < 0.05). Ovalbumin challenge resulted in increases in macrophages and neutrophils in the small airways and parenchyma of sensitized compared with unsensitized rats (p < 0.05). High-dose OX-8 mAb further increased total leukocytes, attributable to increases in neutrophils and eosinophils, retrieved from the large airways and small airways and parenchyma compared with other groups (p < 0.05). Airway responsiveness to methacholine was not significantly different between control and ovalbumin-challenged animals and was not augmented by OX-8 pretreatment. CONCLUSION CD8+ T cells modulate the extent of allergen-induced airway inflammation. However, the enhancement of inflammation was not sufficient to affect airway responsiveness.

Effects of dexamethasone on leukotriene synthesis and airway responses to antigen and leukotriene D4 in rats.

Cysteinyl-leukotrienes (cysteinyl-LTs) are important mediators of both early and late allergen-induced airway responses in atopic asthmatics. We have investigated the effects of glucocorticoids on the in vivo synthesis of cysteinyl-LTs and airway responses to these mediators. Ovalbumin (OA)-sensitized Brown Norway rats, which exhibit early responses and, in most cases, also late responses to late antigen challenge, were treated with either one dose (1 h before antigen challenge) or two doses (2 and 14 h before challenge) of dexamethasone (dex; 300 micrograms/kg). A third group of sensitized rats which did not receive dex served as control animals. All rats were subjected to bile duct cannulation and tracheal intubation 2 h before intratracheal instillation of OA. All of the OA-treated control rats had pronounced early responses (5.5 +/- 1.0 times baseline pulmonary resistance [RL]), whereas 5 of 7 rats had late responses. Biliary levels of N-acetyl-LTE4 increased in all control rats following antigen challenge with a maximum occurring between 1 to 2 h, followed by a decline. There appeared to be a second maximum between 6 to 7 h after challenge, although this could not be demonstrated statistically because of the variability in the response among animals. Treatment with two doses of dex reduced the early response by 57%, completely eliminated the late response, and reduced the levels of N-acetyl-LTE4 in bile by about 80% at all time points.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergen-induced airway responses in rats pretreated with Sephadex

Even though the eosinophil is potentially an important contributor to airway narrowing during the late allergic airway response, direct evidence of its participation is lacking. Therefore, we examined the effects of eosinophilia induced by Sephadex on the magnitude of the late airway response of sensitized rats following allergen challenge. Brown Norway rats were actively sensitized to ovalbumin (OA). At the same time and 14 days later, a test group was administered Sephadex G200 (0.5 mg intravenously). The animals were challenged with an aerosol of OA and pulmonary resistance (RL) was measured over 6 h. The early response to OA reached a peak more rapidly and the magnitude of the late response, measured as the area under the curve ofRL against time, was significantly greater in the Sephadex-treated group (48.3; geometric mean) compared to the control animals (18.9;p<0.02). The percentage of eosinophils was increased in the bronchoalveolar lavage of Sephadex-treated animals (4%) compared to the controls (0.9%;p<0.02) following OA challenge. These results demonstrate that Sephadex induces eosinophilia in Brown Norway rats and is associated with an increase in the late allergic airway response. This is consistent with the hypothesis that the eosinophil is an important determinant of the late response.