Modulation of Fc gamma and complement receptor function by the glycosyl-phosphatidylinositol-anchored form of Fc gamma RIII.
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.
Edberg
J C
JC
Graduate Program in Immunology, Cornell University Medical College, New York, NY 10021.
Kimberly
R P
RP
D000911:Antibodies, Monoclonal; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis; D010766:Phosphorylation; D011951:Receptors, Complement / Q000502:physiology*; D017452:Receptors, IgG / Q000737:chemistry / Q000502:physiology*; D014443:Tyrosine / Q000737:chemistry
D000911:Antibodies, Monoclonal; D017261:Glycosylphosphatidylinositols; D011951:Receptors, Complement; D017452:Receptors, IgG; D014443:Tyrosine; D009240:N-Formylmethionine Leucyl-Phenylalanine