Akerley W L, Guyre P M, Davis B H
Department of Pathology, Dartmouth-Hitchcock Medical Center, Hanover, NH 03756.
Blood. 1991 Feb 1;77(3):607-15.
The high-affinity, type I Ig Fc receptor (Fc gamma RI) for human IgG1, human IgG3, murine IgG2a, and murine IgG3 is highly expressed on monocytes, neutrophils (PMN) in certain disease states, and phagocytes treated with interferon-gamma (IFN-gamma). We studied the activation of the human PMN oxidative burst and stimulated fluid pinocytosis induced by three monoclonal antibodies (MoAbs) directed against Fc gamma RI (CD64) to study the role of this receptor in Fc-mediated cellular activation. All three MoAbs were capable of triggering PMN activation from IFN-gamma-treated PMN when cross-linked with goat antimurine Ig reagents. However, MoAb 197 alone demonstrated a concentration-dependent activation of the oxidative burst without the use of a second cross-linking antibody. The oxidative burst and stimulated fluid pinocytosis responses induced by monomeric MoAb 197 could be elicited only after the IFN-gamma induction of approximately 8,000 Fc gamma RI receptor equivalents and did not occur in freshly isolated or control-cultured PMN. Competitive blocking of Fc binding of MoAb 197 by human IgG or purified Fc fragments inhibited cellular activation. We believe the ability of MoAb 197 to activate these oxidative burst and fluid pinocytic responses was because of its murine IgG2a subclass, which allowed it to function as a trivalent anti-Fc gamma RI antibody binding through the combination of its two FAB regions and the Fc domain. This study demonstrates that the cross-linking of CD64 can activate PMN oxidative and endocytic responses and supports a role for Fc gamma RI in the human neutrophil inflammatory response.
人IgG1、人IgG3、鼠IgG2a和鼠IgG3的高亲和力I型Ig Fc受体（FcγRI）在单核细胞、某些疾病状态下的中性粒细胞（PMN）以及用干扰素-γ（IFN-γ）处理的吞噬细胞上高表达。我们研究了三种针对FcγRI（CD64）的单克隆抗体（MoAb）诱导的人PMN氧化爆发激活和刺激的液体胞饮作用，以研究该受体在Fc介导的细胞激活中的作用。当与山羊抗鼠Ig试剂交联时，所有三种MoAb都能够触发IFN-γ处理的PMN的激活。然而，单独的MoAb 197在不使用第二种交联抗体的情况下表现出氧化爆发的浓度依赖性激活。单体MoAb 197诱导的氧化爆发和刺激的液体胞饮反应只有在IFN-γ诱导约8000个FcγRI受体当量后才会出现，在新鲜分离或对照培养的PMN中不会发生。人IgG或纯化的Fc片段对MoAb 197的Fc结合的竞争性阻断抑制了细胞激活。我们认为MoAb 197激活这些氧化爆发和液体胞饮反应的能力是由于其鼠IgG2a亚类，这使其能够作为一种三价抗FcγRI抗体，通过其两个FAB区域和Fc结构域的结合发挥作用。这项研究表明，CD64的交联可以激活PMN的氧化和内吞反应，并支持FcγRI在人中性粒细胞炎症反应中的作用。
