Edberg J C, Kimberly R P
Graduate Program in Immunology, Cornell University Medical College, New York, NY 10021.
J Immunol. 1994 Jun 15;152(12):5826-35.
Human neutrophils express two structurally distinct receptors for IgG, the transmembrane Fc gamma RII (CD32) and the glycosyl-phosphatidylinositol-linked Fc gamma RIII (CD16). To explore the respective functional roles of Fc gamma RII and Fc gamma RIII, we have used anti-receptor mAb fragments coupled with erythrocytes to quantify both individual and cooperative receptor functions. With individual receptor engagement, Fc gamma RII (E-IV.3) was much more efficient than Fc gamma RIIIB (E-3G8) in initiating phagocytosis (p < 0.001). However, when identical total numbers of receptors were engaged, co-ligation of Fc gamma RII and Fc gamma RIIIB resulted in a phagocytic response, which was: 1) greater than that for either receptor alone (> twofold Fc gamma RII alone (p < 0.001) and > 20-fold Fc gamma RIIIB alone (p < 0.001)); 2) greater than the sum of Fc gamma RII and Fc gamma RIIIB (p < 0.001); and 3) comparable to the phagocytic potential of Fc gamma RII in FMLP pre-activated neutrophils. This synergistic capacity of Fc gamma RIIIB also enabled CR phagocytosis. Furthermore, the capacity for Fc gamma RIIIB to interact synergistically with Fc gamma RII was preserved in FMLP-preactivated neutrophils. The activation of Fc gamma RII by Fc gamma RIIIB was associated with tyrosine phosphorylation of the Fc gamma RII cytoplasmic domain, which is essential for Fc gamma RII function and which, by analogy to the Ig alpha-chain of the B cell Ag receptor complex, the zeta-chain of CD3, and the gamma-chain of some Fc epsilon Rs and Fc gamma Rs, may enhance the binding and activation of Src or Syk family tyrosine kinases. Thus, Fc gamma RIIIB can affect multiple receptor families and play a role in achieving maximal Fc gamma R capacity, even in stimulated neutrophils in inflammatory sites.
人类中性粒细胞表达两种结构不同的IgG受体，跨膜的FcγRII（CD32）和糖基磷脂酰肌醇连接的FcγRIII（CD16）。为了探究FcγRII和FcγRIII各自的功能作用，我们使用了与红细胞偶联的抗受体单克隆抗体片段来量化单个受体和协同受体的功能。在单个受体结合时，FcγRII（E-IV.3）在启动吞噬作用方面比FcγRIIIB（E-3G8）高效得多（p < 0.001）。然而，当相同总数的受体被结合时，FcγRII和FcγRIIIB的共同连接导致了吞噬反应，该反应：1）大于单独任何一种受体的反应（单独的FcγRII大于两倍（p < 0.001），单独的FcγRIIIB大于20倍（p < 0.001））；2）大于FcγRII和FcγRIIIB的总和（p < 0.001）；3）与FMLP预激活的中性粒细胞中FcγRII的吞噬潜力相当。FcγRIIIB的这种协同能力也使得能够进行补体受体吞噬作用。此外，FcγRIIIB与FcγRII协同相互作用的能力在FMLP预激活的中性粒细胞中得以保留。FcγRIIIB对FcγRII的激活与FcγRII细胞质结构域的酪氨酸磷酸化相关，这对FcγRII功能至关重要，并且类似于B细胞抗原受体复合物的Igα链、CD3的ζ链以及一些FcεR和FcγR的γ链，可能增强Src或Syk家族酪氨酸激酶的结合和激活。因此，FcγRIIIB可以影响多个受体家族，并在实现最大FcγR能力方面发挥作用，即使在炎症部位受刺激的中性粒细胞中也是如此。
