Desensitization of the adenylyl cyclase system in peripheral blood mononuclear cells from patients with asthma three hours after allergen challenge.

Abstract

Bronchial hyperreactivity is a common characteristic of patients with asthma and is often associated with enhanced activities of peripheral blood cells. Signal transduction systems are important in regulating cellular activities and can be modified by allergen challenge. Patients with allergic asthma (n = 15) were challenged with house dust mite allergen, resulting in an asthmatic response. Adenylyl cyclase activity was measured in membranes from peripheral blood mononuclear cells before, 3 hours after, and 24 hours after challenge. Allergen challenge proved to have opposite effects in two distinct subgroups of patients. In 10 patients (group I) a heterologous desensitization of the adenylyl cyclase system was observed after challenge, whereas in five patients (group II) an increase in adenylyl cyclase activity was found. Adenylyl cyclase activity before allergen challenge in group II was significantly lower than in group I and comparable to cyclase activity found in group I after allergen challenge. This suggests that in these five patients the adenylyl cyclase system was already desensitized before the start of the study, possibly as a result of natural allergen exposure. Heterologous desensitization in group I was found within 3 hours after allergen challenge, that is before the onset of the late bronchoconstrictive reaction. Because adenylyl cyclase is important in the regulation of cytokine production by mononuclear cells, alteration of cytokine production induced by desensitization of adenylyl cyclase could therefore play a role in the development of the late bronchoconstrictive reaction.