Hundt M, Zielinska-Skowronek M, Schmidt R E
Department of Medicine, Hannover Medical School, Germany.
Arthritis Rheum. 1993 Jul;36(7):974-82. doi: 10.1002/art.1780360715.
The role of Fc gamma receptors (Fc gamma R) in type I cryoglobulinemia was investigated to characterize novel mechanisms of neutrophil activation in the pathogenesis of leukocytoclastic vasculitis.
Neutrophils from healthy donors were incubated with purified monoclonal IgG1 kappa cryoglobulin complexes in vitro. Changes in surface antigen expression and mechanisms of intracellular hydrogen peroxide production and calcium release were measured by flow cytometry.
After incubation for 2 hours, surface expression of Fc gamma RI (CD64), CD66, and CD67 was up-regulated; Fc gamma RII (CDw32), Fc gamma RIII (CD16), and LAM-1 were down-regulated. Using solubilized and complexed cryoglobulins, it was demonstrated that complex formation is necessary to induce intracellular H2O2 production and calcium release from intracellular stores. Both H2O2 generation and calcium mobilization could be inhibited by pretreatment with F(ab')2 fragments of monoclonal antibodies (MAb) against Fc gamma RIII. In contrast, Fab fragments of anti-Fc gamma RII MAb failed to block these activations. Neither the cryoglobulin complex-induced production of H2O2 nor the increase in cytoplasmic calcium was affected by treatment with pertussis toxin, which suggests that pertussis toxin-sensitive G proteins are not involved in signal transduction.
These results indicate that Fc gamma RIII plays a major role in the pathogenesis of leukocytoclastic vasculitis.
研究Fcγ受体（FcγR）在I型冷球蛋白血症中的作用，以明确白细胞破碎性血管炎发病机制中嗜中性粒细胞激活的新机制。
将健康供体的嗜中性粒细胞与纯化的单克隆IgG1κ冷球蛋白复合物在体外孵育。通过流式细胞术检测表面抗原表达的变化以及细胞内过氧化氢产生和钙释放的机制。
孵育2小时后，FcγRI（CD64）、CD66和CD67的表面表达上调；FcγRII（CDw32）、FcγRIII（CD16）和LAM-1的表面表达下调。使用可溶解的和复合的冷球蛋白，证明复合物形成对于诱导细胞内H2O2产生和从细胞内储存中释放钙是必要的。用抗FcγRIII单克隆抗体（MAb）的F(ab')2片段预处理可抑制H2O2生成和钙动员。相反，抗FcγRII MAb的Fab片段未能阻断这些激活。用百日咳毒素处理既不影响冷球蛋白复合物诱导的H2O2产生，也不影响细胞质钙的增加，这表明百日咳毒素敏感的G蛋白不参与信号转导。
这些结果表明FcγRIII在白细胞破碎性血管炎的发病机制中起主要作用。
