Debets J M, Van de Winkel J G, Ceuppens J L, Dieteren I E, Buurman W A
Department of Surgery, University of Limburg, Maastricht, The Netherlands.
J Immunol. 1990 Feb 15;144(4):1304-10.
Cross-linking of Fc gamma R on human monocytes with human IgG has been shown to induce secretion of the inflammatory and immunoregulatory cytokine TNF. In the present study we examined the role of both constitutively expressed monocyte Fc gamma R, the 72-kDa high affinity Fc gamma R (Fc gamma RI), and the 40-kDa low affinity receptor (Fc gamma RII), in the induction of TNF secretion. On the basis of preferential binding of the Fc moiety of murine mAb of different isotype, Fc gamma RI and Fc gamma RII were selectively cross-linked by using either solid-phase murine (m)IgG2a, or solid-phase mIgG1, respectively. On freshly isolated, untreated monocytes only cross-linking of Fc gamma RI with solid-phase mIgG2a induced TNF secretion. The interaction between Fc gamma RII and mIgG1 could be enhanced by treatment of monocytes with proteases or with the desialylating enzyme neuraminidase. After treatment of monocytes with these enzymes, TNF secretion was effectively induced by solid-phase mIgG1, apparently through cross-linking of Fc gamma RII. However, mIgG1-induced TNF secretion differed between protease-treated monocytes from high responder individuals and monocytes from low responder individuals, TNF secretion being considerably less in the latter population. Protease-treated monocytes and mononuclear cells from individuals with an inherited defect in cell membrane expression of Fc gamma RI were induced to secrete TNF by solid-phase human IgG, confirming the capacity of Fc gamma RII to induce TNF secretion. It was not possible to induce TNF secretion by cross-linking Fc gamma RI or Fc gamma RII with anti-Fc gamma R mAb and soluble or solid-phase anti-mIgG, indicating that high affinity Fc-Fc gamma R interactions are necessary to induce release of this cytokine.
人单核细胞上的FcγR与人类IgG交联已被证明可诱导炎症和免疫调节细胞因子TNF的分泌。在本研究中，我们检测了组成性表达的单核细胞FcγR，即72 kDa高亲和力FcγR（FcγRI）和40 kDa低亲和力受体（FcγRII）在诱导TNF分泌中的作用。根据不同同种型鼠单克隆抗体Fc部分的优先结合情况，分别使用固相鼠（m）IgG2a或固相mIgG1选择性交联FcγRI和FcγRII。在新鲜分离、未处理的单核细胞上，只有FcγRI与固相mIgG2a交联可诱导TNF分泌。用蛋白酶或去唾液酸酶神经氨酸酶处理单核细胞可增强FcγRII与mIgG1之间的相互作用。用这些酶处理单核细胞后，固相mIgG1可有效诱导TNF分泌，显然是通过FcγRII的交联。然而，mIgG1诱导的TNF分泌在高反应个体的蛋白酶处理单核细胞和低反应个体的单核细胞之间存在差异，后者群体中的TNF分泌明显较少。蛋白酶处理的单核细胞和来自FcγRI细胞膜表达存在遗传性缺陷个体的单核细胞被固相人IgG诱导分泌TNF，证实了FcγRII诱导TNF分泌的能力。用抗FcγR单克隆抗体和可溶性或固相抗mIgG交联FcγRI或FcγRII无法诱导TNF分泌，表明高亲和力Fc-FcγR相互作用是诱导该细胞因子释放所必需的。
