IgG Receptor FcγRⅡB And FcγRⅢA Participate In Murine Allergic Asthma

Objective:To explore the effect of IgG FcγRⅢA and FcγRⅡB in murine allergic asthma.Methods:The 8-10 week old male wide tpye（WT）C57BL/6,FcγRⅡB^-/-and FcγRⅢA^-/-mice were randomly divided into the control group and the model group（n=5-6 per group）.Mice in the model group were sensitized with ovalbumin（OVA）adjuvanted in aluminnium hydroxide（Alum）,and then exposed to OVA aerosol,while mice in the control group reveived equivalent PBS instead.Within 24 h after the final challenge,the total cell count and the amounts of different cell populations in the broncho-alveolar lavage fluid（BALF）were assessed.The proliferation of splenocytes in response to OVA re-exposure was determined by CCK-8.The OVA-specific IgE and OVA-specific IgG in the serum were measured by enzyme-linked immunosorbent assay（ELISA）.The concentrations of cytokines in the BALF,serum and supernatants from splenocyte-cultures were examined using cytometric beads array（CBA）assay.The pathological changes of lung tissue were observed following HE-and PAS-staining with a microscope.Cell-influx into the lung tissue and chemokine mRNA expression in the flamed lung were evaluated using flow cytometric assay or quatitative real time-PCR.The mRNA expression of FcγRⅡB,FcγRⅡA and FcγRⅢA on peripheral blood mononuclear cells（PBMC）together with the circulating IgE levels in the serum from patients with allergic asthma were analysed.Results:Compared to the WT mice,asmatic mice deficient in FcγRⅡB^-/-presented elevated OVA-specific IgE,OVA-specific IgG（P<0.05）and IL-6,TNF-αin the serum（P<0.01）,whereas FcγRⅢA^-/-mice delivered increased OVA-specific IgE,IgG,IgG₁ and IgG_2b in the serum（P<0.05 or P<0.01）after asthmatic stimulation.In response to allergen-challenge,the total cell number and amounts of individual cell type in BALF from FcγRⅡB^-/-mice were noticeably increased（P<0.001）,and the IL-6,TNF-αsecretion is also increased（P<0.01 or P<0.05）.No obvious change was observed in BALF from asthmatic FcγRⅢA^-/-mice compared to the WT mice.Lung pathological changes and mucus secretions were severer in FcγRⅡB^-/-asthmatic mice than that in the WT mice.Dendritic cells and CCL2 expression in asthmatic lungs from FcγRⅡB^-/-and FcγRⅢA^-/-mice were increased remarkably compared to WT mice（P<0.05,P<0.01 or P<0.001）.FcγRⅡB lacking promoted the proliferation of splenocytes and the cytokine secretions including IL-5,IL-6,IL-10,IL-13 and TNF in the supernatant of splenocyte cultures on the OVA-provocation（P<0.01 or P<0.05）.The expression levels of human FcγRⅡB but not FcγRⅡA were negatively correlated to serum levels of IgE in human asthma patients.Conclusion:The inhibitory receptor FcγRⅡB can inhibit allergic asthma,but we did not find major evidence demonstrating an immune inhibitory role of mouse FcγRⅢA in this OVA-induced mouse asthma model.