Inhibitory effect of an small peptide that interferes with Fc?-receptor recognition on antineutrophil cytoplasmic antibodies induced activity of neutrophils / 中华风湿病学杂志

ABSTRACT

Objective Despite regular treatment,antineutrophil eytoplasmie antibodies(ANCA)asso- ciated systemic vasculitis(AASV),in which the role of Fc?Rs has been established,are still associated with significant long-term mortality and remain an important cause of end-stage renal failure.ANCA plays an im- portant role in the pathogenisis of primary systemic small vessel vasculitis(PSV)by their potential to activate neutrophils.Because the interaction between ANCA and its receptors on the Fc portion of immunoglobulins (Fc?R)on neutrophils is essential in the activation process,we investigate the inhibitory,effect of tg19320 on ANCA induced activation of neutrophils,which is a tetrameric tripeptide that interferes with IgG/Fe?Rs in- teraction.Methods We prepared tg19320 by solid-phase peptide syntbesis.The binding between tg19320 and human IgG was assessed by enzyme-linked immunosorbent assay.The biological activity of tg19320 to intefere with FcF?receptor recognition was identified by rosette formation assay.ANCA IgG was prepared from the sera of active Wegener's granulomatosis(WG)and microscopic polyangiitis(MPA)patients.Neu- trophils isolated from the blood of healthy volunteers were primed with TNF-?(2 ng/ml)and then incubated with ANCA IgG(200?g/ml),or pretreated with tg19320(2.5 mg/ml)and then added with ANCA IgG.Su- peroxide burst of neutrophils was determined by Ferri-cytochrome reduction assay.Results We found that tg19320 bound tightly to human IgG in a dose dependent manner and the inhibition of the rosette formation between SRBC-IgG and U937 cells was statistically significant(20.3% vs 53.2%,P