A LINK BETWEEN CATALYTIC ACTIVITY, IGE-INDEPENDENT MAST-CELL ACTIVATION, AND ALLERGENICITY OF BEE VENOM PHOSPHOLIPASE A(2)

作者:DUDLER T; MACHADO DC; KOLBE L; ANNAND RR; RHODES N; GELB MH; KOELSCH E; SUTER M; HELM BA
来源:The Journal of Immunology, 1995, 155(5): 2605-2613.

摘要

The molecular and cellular mechanisms controlling Ab isotype selection following encounter of a given Ag are still unclear, although the regulatory role of cytokines is established. In the present study we explored the possibility that the nonimmunologic interaction of an allergen with cells of the innate immune system might result in a release of mediators that promote IgE isotype selection in adaptive responses. Using the bee venom allergen phospholipase A(2) (PLA(2)) and a mutant variant lacking enzymatic function, we show that PLA(2), but not its catalytically inactive variant, is able to induce IgE-independent mediator release, including IL-4, from rodent mast cells. Assessing the in vivo relevance of these observations, we find that repeated injections of low doses of active enzyme into mice induce the synthesis of high levels of PLA(2)-specific IgE, while immunization with the inactive form yields no detectable IgE response. Both Ags were similarly immunogenic when high doses of Ag were used for immunization. These findings suggest that mast cells might be a source of IL-4 at the onset of specific immunity against sources of allergens such as bee venom that contain PLA(2) and support the concept that the biologic action of an Ag on cells of the innate immune system can play a key role in determining adaptive immune responses.

  • 出版日期1995-9-1