Capsoni F, Minonzio F, Ongari A M, Colombo G, Rizzardi G P, Bonara P, D'Arminio-Monforte A, Zanussi C
Institute of Internal Medicine, University of Milan, Italy.
Clin Exp Immunol. 1992 Nov;90(2):175-80. doi: 10.1111/j.1365-2249.1992.tb07924.x.
Interferon-gamma (IFN-gamma) induces de novo expression of IgG Fc receptor type I (FcRI) on neutrophils and significantly raises the level of these receptors on monocytes. Since increased concentrations of IFN-gamma have been observed in sera from patients with HIV infection, FcRI expression might also be increased on these subjects' phagocytes. FcRI expression was assessed by indirect immunofluorescence staining of phagocytes in whole blood from 40 healthy controls and 55 HIV+ subjects, 24 belonging to CDC class III and 31 to CDC class IV; 42 were intravenous drug abusers (IVDA) and 13 were homosexual men. Plasma levels of IFN-gamma were measured using a modified immunoradiometric assay. The mean linear fluorescence intensity, used as a relative measure of receptor expression, was significantly higher on unseparated neutrophils from HIV+ subjects in CDC classes III (P < 0.001) and IV (P < 0.0001) than from controls. Similar changes in FcRI expression were observed on monocytes from HIV+ subjects. While no differences were observed between IVDA and homosexual HIV+ patients, there was a significant association between FcRI expression and the patients' CDC stage, those in class IV having the highest FcRI levels. Plasma IFN-gamma concentrations were significantly higher in HIV+ patients than in controls and a positive correlation with the stages of HIV infection was again observed. FcRI expression was also increased on freshly purified neutrophils from five HIV+ patients in CDC class IV but did not increase further after 18 h incubation with IFN-gamma, a treatment that up-regulated FcRI expression on control neutrophils. These data suggest that: (i) FcRI evaluation may be a sensitive marker for the biological activity of IFN-gamma in vivo; (ii) phagocytes from HIV+ subjects are activated in vivo by IFN-gamma, expressing increased levels of FcRI; (iii) these IFN-gamma-activated cells may play a role in the pathogenesis of AIDS.
干扰素-γ(IFN-γ)可诱导中性粒细胞上从头表达I型IgG Fc受体(FcRI),并显著提高单核细胞上这些受体的水平。由于在HIV感染患者的血清中观察到IFN-γ浓度升高,这些受试者吞噬细胞上的FcRI表达可能也会增加。通过间接免疫荧光染色评估40名健康对照者和55名HIV阳性受试者全血中吞噬细胞的FcRI表达,其中24名属于疾病控制与预防中心(CDC)III级,31名属于CDC IV级;42名是静脉吸毒者(IVDA),13名是男同性恋者。使用改良的免疫放射分析方法测量血浆中IFN-γ的水平。用作受体表达相对指标的平均线性荧光强度,在CDC III级(P<0.001)和IV级(P<0.0001)的HIV阳性受试者未分离的中性粒细胞上显著高于对照者。在HIV阳性受试者的单核细胞上也观察到FcRI表达有类似变化。虽然在IVDA和HIV阳性同性恋患者之间未观察到差异,但FcRI表达与患者的CDC分期之间存在显著关联,IV级患者的FcRI水平最高。HIV阳性患者的血浆IFN-γ浓度显著高于对照者,并且再次观察到与HIV感染分期呈正相关。在来自5名CDC IV级HIV阳性患者的新鲜纯化中性粒细胞上,FcRI表达也增加,但在与IFN-γ孵育18小时后未进一步增加,而该处理可上调对照中性粒细胞上的FcRI表达。这些数据表明:(i)FcRI评估可能是体内IFN-γ生物活性的敏感标志物;(ii)HIV阳性受试者的吞噬细胞在体内被IFN-γ激活,表达增加的FcRI水平;(iii)这些IFN-γ激活的细胞可能在艾滋病发病机制中起作用。