ALLERGEN-SPECIFIC IGG1 AND IGG3 THROUGH FC-GAMMA-RII INDUCE EOSINOPHIL DEGRANULATION

Evidence suggests that eosinophils contribute to inflammation in bronc hial asthma by releasing chemical mediators and cytotoxic granule prot eins, To investigate the mechanism of eosinophil degranulation in asth ma, we established an in vitro model of allergen-induced degranulation , We treated tissue culture plates with short ragweed pollen (SRW) ext ract and sera from either normal donors or SRW-sensitive patients with asthma, Eosinophils were incubated in the wells and degranulation was assessed by measurement of eosinophil-derived neurotoxin in supernata nts, We detected degranulation only when sera from SRW-sensitive patie nts were reacted with SRW. Anti-IgG and anti-Fc(gamma) RII mAb, but no t anti-IgE or anti-Fc(epsilon)RII mAb, abolished the degranulation. Ig G-depleted serum did not induce degranulation; IgE-depleted serum trig gered as much degranulation as untreated serum, Furthermore, serum lev els of SRW-specific IgG1 or IgG3 correlated with the amounts of releas ed eosinophil-derived neurotoxin. When eosinophils were cultured in we lls coated with purified IgG or IgE, eosinophil degranulation was obse rved only with IgG, Finally, human IgG1 and IgG3, and less consistentl y IgG2, but not IgG4, induced degranulation. Thus, sera from patients with SEW-sensitive asthma induce eosinophil degranulation in vitro thr ough antigen-specific IgG1 and IgG3 antibodies. These antibodies may b e responsible for degranulation of eosinophils in inflammatory reactio ns, such as bronchial asthma.