Carbamoyl phosphate synthetase: a tunnel runs through it

BACKGROUND: Sensitivity to specific allergens and increased sensitivity to common spasmogens are characteristic features of allergic asthma and are also features demonstrated by tissues passively sensitized with serum from atopic donors, displaying high levels of IgE. It is evident that the specific response to allergen is related to circulating levels of allergen-specific IgE, but it is unclear whether the histamine hypersensitivity is also related to this immunoglobulin. OBJECTIVE: The objective was to deplete IgE in the serum of a donor with high levels of total and allergen-specific IgE and compare specific-allergen sensitivity and sensitivity to histamine in tissues passively sensitized with either the whole serum or the IgE-depleted serum. METHODS: Serum from a Dermatophagoides farinae-sensitive asthmatic (total IgE = 1047 U/mL, D. farinae-specific IgE > 17.5 U/mL) was subjected to an immunomagnetic separation technique to reduce the levels of IgE (total and specific) to below 10 U/mL. Bronchial tissue from six non-atopic donors was then passively sensitized overnight with either the whole serum or IgE-depleted serum and D. farinae and histamine sensitivity were evaluated the next day using standard organ bath techniques. RESULTS: Passive sensitization with the whole serum resulted in the development of sensitivity to D. farinae and increased sensitivity to histamine (750+/-169 mg contraction to 10 U/mL D. farinae, histamine pEC50 5.64+/-0.16 and max. 813+/-109 mg in sensitized vs 37+/-34 mg contraction to 10 U/mL D. farinae histamine pEC50 5.05+/-0.23 and max. 490+/-84 in non-sensitized tissues, P>0.05). Incubation with IgE-depleted serum still produced histamine hypersensitivity (histamine pEC50 5.57+/-0.16 and max. 737+/-70 mg P>0.05), but no significant response to allergen was detected (20+/-13 mg contraction to 10 U/mL D. farinae). CONCLUSION: These results demonstrate, that increased reactivity to histamine and airway contraction to allergen induced by passive sensitization, occur through independent mechanisms and that, unlike allergen-sensitivity, histamine hypersensitivity is caused by a serum factor other than IgE.