Lack of systemic anaphylaxis and aeroallergen-induced airway plasma extravasation in allergic immunoglobulin-deficient mice.

BACKGROUND: In Ig-deficient mice allergen challenge-induced pulmonary late phase inflammation is at least as pronounced as in wild-type animals. This study investigates immediate hypersensitivity responses in these mice. METHODS: To examine the acute plasma extravasation response in airway tissue, immunized Ig-deficient and wild-type mice and sham-immunized wild-type controls were subjected to 15 min ovalbumin aerosol challenge. 125I-albumin was injected (i.v.) 1 min prior to challenge. Immediately after challenge 131I-albumin was injected and the experiment was terminated. Plasma and trachea were analyzed for 125I and 131I, and the amount of extravasated plasma in the trachea was calculated. To study the development of systemic anaphylaxis immunized Ig-deficient and wild-type animals received intravenous allergen challenge followed by determination of mast cell responses and plasma histamine levels. RESULTS: Allergen aerosol-exposed immunized wild-type mice exhibited marked plasma extravasation in the trachea (pd0.01 vs. wild-type controls), but in the corresponding Ig-deficient mice there was no increased extravasation. Immunized Ig-deficient mice receiving intravenous allergen challenge were resistant to anaphylactic shock. By contrast, the wild-type animals developed systemic anaphylaxis, accompanied by plasma extravasation, mast cell degranulation, elevated plasma histamine and rapid death. CONCLUSION: The present data are evidence that immunoglobulins are crucial for the development of immediate (type 1) responses. These findings together with our previous observations on late-phase pulmonary responses suggest that immediate hypersensitivity processes are unimportant for development of the late phase inflammation in the respiratory tract of mice.

Allergen challenge-induced extravasation of plasma in mouse airways.

BACKGROUND: Mouse models are extensively used to study genetic and immunological mechanisms of potential importance to inflammatory airway diseases, e.g. asthma. However, the airway pathophysiology in allergic mice has received less attention. For example, plasma extravasation and the ensuing tissue-deposition of plasma proteins, which is a hallmark of inflammation, has not been examined in allergic mice. OBJECTIVE: This study aims to examine the vascular permeability and the distribution of plasma proteins in mouse airways following exposure to allergen and serotonin. METHODS: Extravasated plasma was quantified by a dual isotop technique using intravascular (131I-albumin) and extrasvascular (125I-albumin) plasma tracers. Histological visualization of fibrinogen and colloidal gold revealed the tissue distribution of extravasated plasma. RESULTS: Allergen aerosol exposure (3% OVA, 15min) of sensitized animals resulted in a marked plasma extravasation response in the trachea (P < 0.01) and the bronchi but not in the lung parenchyma. A similar extravasation response was induced by serotonin (P<0.001). Extravasating vessels (assessed by Monastral blue dye) were identified as intercartilaginous venules. Extravasated plasma abounded in the subepithelial tissue but was absent in the epithelium and airway lumen. The allergen-induced response was dose-dependently inhibited by iv administration of formoterol (P < 0.001), a vascular antipermeability agent. CONCLUSION: The present study demonstrates that serotonin and allergen challenge of sensitized mice increase airway venular permeability to cause transient extravasation and lamina propria distribution of plasma in the large airways. We suggest that the extravasation response is a useful measure of the intensity and the distribution of active inflammation

Effect of glucocorticosteroid treatment on ovalbumin-induced IgE-mediated immediate and late allergic response in guinea pig.

The effect of glucocorticosteroid (GCS) treatment on ovalbumine-induced IgE-mediated immediate and late allergic response was studied in sensitized guinea pigs. The results show that the GCS budesonide (BUD) inhibits the allergen-induced IgE-mediated immediate and late bronchial obstruction. The effect on the early reaction is correlated to the inhibition of leukotrienes and histamine release. The importance of mediator release inhibition for the antianaphylactic effect of GCS is discussed. In examining the effect on the late reaction, it was found that BUD had to be present during the early reaction but did not inhibit the early reaction. Furthermore, the effect on the late reaction was correlated to the inhibition of vascular leakage but not to the infiltration of inflammatory cells as examined in bronchoalveolar lavage. The results indicate that some triggering factors important for the development of the late reaction are released during the early reaction. Inhibition of the release of that factor or the activation of inflammatory cells by that factor might be the mechanism behind the antiinflammatory activities of GCS.