Cell-specific, activation-dependent regulation of neutrophil CD32A ligand-binding function

Shanmugam Nagarajan, Kala Venkiteswaran, Michael Anderson, Umar Sayed, Cheng Zhu, Periasamy Selvaraj

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Neutrophils express 2 low-affinity FcγR, FcγRIIIB (CD16B), and FcγRIIA (CD32A). CD16B is a glycosyl-phosphatidyl inositol-anchored molecule, whereas CD32A is a polypeptide-anchored molecule. These 2 receptors also differ in their signaling. The biological significance of coexpression of 2 FcγRs with distinct membrane anchors and signaling capacities is not clearly understood. Using neutrophils from a CD16B-deficient donor and normal neutrophils treated with anti-CD16 monoclonal antibodies, the authors demonstrated that affinity modulation of CD32A is one of the mechanisms by which neutrophils regulate their FcγR-dependent functions. Neutrophils isolated from a CD16B- donor rosetted poorly with sheep erythrocytes opsonized with rabbit IgG (EA) (12% ± 2% versus 80% ± 6% for control) and were unable to mediate immunophagocytosis. However, activation of CD16B- neutrophils with fMLP, a bacterial chemotactic peptide, increased the CD32A- dependent EA rosetting to 58%. The CD32A-dependent rosetting of fMLP- activated normal neutrophils also increased nearly 5-fold, but there was no increase in CD32A expression. The CD32A-dependent immune complex (IC) binding was also increased in activated neutrophils. This affinity regulation was not observed with CD32A expressed on Chinese hamster ovary cells. These results suggest that in resting neutrophils CD32A is in a low-affinity state and that these cells primarily engage CD16B for IC binding. However, once the neutrophils are activated, the CD32A is converted to a high-affinity state that leads to CD32A-dependent ligand binding and signaling. These results suggest that neutrophils adopt a novel strategy to engage the 2 different FcγR selectively during physiologic and pathologic conditions to carry out their functions efficiently.

Original languageEnglish (US)
Pages (from-to)1069-1077
Number of pages9
JournalBlood
Volume95
Issue number3
DOIs
StatePublished - Feb 1 2000

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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