Lack of Systemic Anaphylaxis and Aeroallergen–Induced Airway Plasma Extravasation in Allergic Immunoglobulin–Deficient Mice

Abstract

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 recieved 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.

Role of dendritic cells and Th2 lymphocytes in asthma: Lessons from eosinophilic airway inflammation in the mouse

“…Similarly, B cells do not seem to contribute significantly to the secondary immune response and the development of airway eosinophilia, although they might contribute to plasma extravasation during the early phase response to OVA aerosol and to bronchial hyperreactivity (see below) (Hamelmann et al, 1997b;Korsgren et al, 1997Korsgren et al, , 1999a. Recently, it was also shown that airway eosinophils express MHC class II and the costimulatory molecules CD80 and CD86, effectively contributing to the stimulation of effector Th2 cells in the lungs and lymph nodes of sensitized mice (Korsgren et al, 1997;Mathur et al, 1999;Shi et al, 2000).…”

Dendritic Cells as Regulators of the Immune Response to Inhaled Allergen: Recent Findings in Animal Models of Asthma

“…Similarly, B cells do not seem to contribute significantly to the secondary immune response and the development of airway eosinophilia, although they might contribute to plasma extravasation during the early-phase response to OVA aerosol and to bronchial hyperreactivity [87, 100, 101]. Recently, it was also shown that airway eosinophils express MHC class II and the co-stimulatory molecules CD80 and CD86, effectively contributing to the stimulation of effector Th2 cells in the lungs and lymph nodes of sensitised mice [80, 87, 102].…”

In vivo paradigms of diseased airway mucosa: selected aspects of innate immunity and eosinophils

“…Briefly, extensive eosinophilia in airway-lungs (7) and regional lymph nodes (7) was demonstrated in immunized and allergen-challenged homozygous mutant Cs 7BL/6 mice that lack B cells and all Ig. Hence, there was a complete separation of early and late-phase responses (14). The imme&ate allergen challenge-induced responses were completely blunted in these animals.…”