title: IgE cross-linking critically impairs human monocyte function by blocking phagocytosis.
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.
authors: Department of Immunology, UT Southwestern Medical Center, Dallas, Tex 75390, USA.
authors: David M
authors: DM
authors: Pyle
authors: Victoria S
authors: VS
authors: Yang
authors: Rebecca S
authors: RS
authors: Gruchalla
authors: J David
authors: JD
authors: Farrar
authors: Michelle A
authors: MA
authors: Gill
mesh_terms: D000293:Adolescent; D000328:Adult; D000954:Antigens, Surface / Q000276:immunology; D001491:Basophils / Q000276:immunology / Q000502:physiology; D002478:Cells, Cultured; D004926:Escherichia coli / Q000276:immunology / Q000502:physiology; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D016753:Interleukin-10 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology*; D017455:Receptors, IgE / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D055815:Young Adult
chemical_list: D000954:Antigens, Surface; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D017455:Receptors, IgE; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007073:Immunoglobulin E
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