We postulate that ANXA1 is an important regulatory factor in the development of allergic disease and dysregulation of its expression can lead to pathological changes which may affect disease progression.

SummaryThe role of basophils in an anaphylactic response is well recognized but is usually masked by mast cells, which contain similar mediators for the induction of generalized vasodilatation and laryngeal constriction. The rapid onset of systemic anaphylactic symptoms, particularly in insect stings and ingested food, suggest that basophils, a circulating pool of cells containing histamine and other potent mediators such as leukotrienes, may be more involved in systemic anaphylaxis than originally thought. We wished to examine if secretory phospholipase A2, a systemic allergen found in honey bee venom (HBVsPLA2) may activate basophils directly leading to rapid systemic mediator release. Basophils were isolated from human blood and stimulated with increasing concentrations of HBV-sPLA2. We found that physiological concentrations of HBV-sPLA2 induce rapid leukotriene C4 production from purified human basophils within 5 min, while interleukin (IL)-4 expression and production was induced at later time-points. Histamine release was not induced, signifying that HBV-sPLA2 did not induce generalized degranulation. Surface expression of CD63, CD69 and CD11b were up-regulated following HBV-sPLA2 treatment. Stimulation of basophils with anti-immunoglobulin E (IgE) following treatment with HBV-sPLA2 did not induce more leukotriene release. To investigate the mechanism of leukotriene production, 9-12 octadecadiynioc acid, a cyclooxygenase-1 (COX-1) and 15-lipoxygenase inhibitor, was used and this abrogated leukotriene production. These results indicate that HBV-sPLA2 can directly activate human basophils in vitro to induce leukotriene production.

Allergic asthma is a complex disorder characterized by airway inflammation and reversible airway obstruction and airway hyperresponsiveness. Glucocorticoids are currently the most effective anti-inflammatory therapy for asthma. Annexin-1 is an endogenous anti-inflammatory protein responsible for many anti-inflammatory effects of glucocorticoids. Here we show in a mouse model of asthma, that annexin-1 deficient mice do not exhibit enhanced inflammation, such as eosinophil infiltration, but exhibited higher antibody production. In particular, allergen-specific and total IgE levels, as well as allergen-specific IgG1, IgG2a and IgG2b serum levels were significantly higher in annexin-1 deficient mice. Our results in annexin-1 deficient mice demonstrate that annexin-1 may play a regulatory role in the intrinsic development of allergy.