IgE cross-linking critically impairs human monocyte function by blocking phagocytosis

David M. Pyle, Victoria S. Yang, Rebecca S. Gruchalla, J. David Farrar, Michelle A. Gill

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Background: IgE cross-linking triggers many cellular processes that drive allergic disease. While the role of IgE in mediating allergic responses is best described on basophils and mast cells, expression of the high-affinity IgE receptor on other innate immune cells, including monocytes, suggests that it may affect the function of these cells in allergic environments. Objective: To determine the effect of IgE cross-linking on the function of human monocytes. Methods: Monocytes purified from healthy donor blood samples were cultured for 4 to 96 hours with media alone, a cross-linking anti-IgE antibody or control IgG. Surface CD14 and CD64 expression and secreted cytokine concentrations were determined. Monocyte function was determined by assessing (1) phagocytosis of Escherichia coli or apoptotic HEp2 cells and (2) killing of intracellular E coli. Select experiments were performed on monocytes obtained from participants with elevated versus normal serum IgE concentrations. Results: IgE cross-linking on monocytes increased CD14 expression and induced secretion of TNF-α, IL-6, and autoregulatory IL-10. These effects were greatest in individuals with elevated serum IgE concentrations. In contrast, IgE cross-linking reduced CD64 expression and significantly impaired phagocytic function without disrupting the capacity of monocytes to kill bacteria. Conclusions: IgE cross-linking drives monocyte proinflammatory processes and autoregulatory IL-10 in a serum IgE-dependent manner. In contrast, monocyte phagocytic function is critically impaired by IgE cross-linking. Our findings suggest that IgE cross-linking on monocytes may contribute to allergic disease by both enhancing detrimental inflammatory responses and concomitantly crippling phagocytosis, a primary mechanism used by these cells to resolve inflammation.

Original languageEnglish (US)
Pages (from-to)491-500.e5
JournalJournal of Allergy and Clinical Immunology
Volume131
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • FcεRI
  • IgE
  • IgE cross-linking
  • Monocyte
  • allergy
  • apoptotic debris
  • autoregulatory
  • phagocytosis
  • proinflammatory

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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