Cross-linking of Fc gamma receptor IIa and Fc gamma receptor IIIb induces different proadhesive phenotypes on human neutrophils

J Immunol. 1997 Oct 15;159(8):3940-8.


Activation of polymorphonuclear leukocytes (PMN) plays an important role in vascular injury associated with systemic vasculitis and in models of autoantibody- and immune complex-mediated disease. The potential role of intravascular activation of PMN, however, is confounded by the observation that some stimuli injected i.v. (e.g., IL-8 and C5a) lead to L-selectin shedding by PMN, which inhibits attachment to endothelium and may be functionally anti-inflammatory. To explore the impact of Fc gamma receptor (Fc gamma R)-mediated activation on the PMN adhesive phenotype, Fc gamma RIIa (CD32) and Fc gamma RIIIb (Cd16) were targeted with receptor-specific reagents, and the expression of adhesion molecules-mediating rolling (L-selectin) and firm adhesion (CD11b/CD18) was measured. Engagement of either Fc gamma RIIa or Fc gamma RIIIb leads to activation, demonstrated by degranulation (upregulation of CD66b), and to increased expression of total CD11b/CD18 and functional CD11b/CD18 (I-domain). In contrast, L-selectin shedding induced by PMN Fc gamma R was divergent. Despite the 5- to 10-fold greater expression and engagement at saturation, activation via Fc gamma RIIIb led to little or no change in L-selectin expression. Stimulation of PMN with intact murine anti-receptor IgG1 showed a contribution of Fc gamma RIIa receptor polymorphisms, underscoring the direct influences of Fc gamma R allotypes on receptor function. These observations suggest that Fc gamma RIIIb-mediated activation of circulating PMN may lead to a proadhesive phenotype likely to promote systemic vascular damage. This Fc gamma R-mediated adhesive phenotype will vary with the receptors engaged and their allotypes, which, in turn, reflect properties of the immune complex and the genetics of the host.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Antibodies, Antineutrophil Cytoplasmic / pharmacology
  • CD18 Antigens / biosynthesis
  • Cell Adhesion / genetics
  • Cell Adhesion / immunology
  • Cross-Linking Reagents
  • Cyclic AMP / blood
  • Down-Regulation / immunology
  • Epitopes / biosynthesis
  • Humans
  • Immunophenotyping
  • L-Selectin / biosynthesis
  • L-Selectin / immunology
  • Macrophage-1 Antigen / biosynthesis
  • Neutrophil Activation / immunology*
  • Neutrophils / immunology*
  • Neutrophils / metabolism*
  • Neutrophils / physiology
  • Protein Structure, Tertiary
  • Receptors, IgG / antagonists & inhibitors
  • Receptors, IgG / blood*
  • Receptors, IgG / genetics
  • Receptors, IgG / physiology*
  • Up-Regulation / immunology


  • Antibodies, Antineutrophil Cytoplasmic
  • CD18 Antigens
  • Cross-Linking Reagents
  • Epitopes
  • Macrophage-1 Antigen
  • Receptors, IgG
  • L-Selectin
  • Cyclic AMP