IgE modulates neutrophil survival in asthma: role of mitochondrial pathway

J Immunol. 2007 Feb 15;178(4):2535-41. doi: 10.4049/jimmunol.178.4.2535.

Abstract

The high-affinity IgE receptor (FcepsilonRI) has recently been reported to be expressed by neutrophils in atopic asthmatic individuals, leading to speculations that IgE could influence biological functions of these cells. In this study, we demonstrate that monomeric human IgE delayed spontaneous apoptosis of primary human neutrophils from atopic asthmatics in vitro. This effect was not dependent on FcepsilonRI cross-linking or autocrine release of soluble mediators; however, it was associated with increased expression of the antiapoptotic myeloid cell leukemia-1 protein, retention of the proapoptotic molecule Bax in the cytoplasm, decreased release of Smac from mitochondria, and reduced caspase-3 activity. Taken together, our results indicate that in vitro IgE can delay programmed cell death of neutrophils from allergic asthmatics and this may possibly contribute to neutrophilic inflammation in atopic asthma.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / immunology*
  • Apoptosis Regulatory Proteins
  • Asthma / immunology*
  • Asthma / metabolism
  • Asthma / pathology
  • Autocrine Communication / immunology
  • Caspase 3 / immunology
  • Caspase 3 / metabolism
  • Cell Survival / immunology
  • Cytoplasm / immunology
  • Cytoplasm / metabolism
  • Gene Expression Regulation / immunology
  • Humans
  • Immunoglobulin E / immunology*
  • Immunoglobulin E / metabolism
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Intracellular Signaling Peptides and Proteins / immunology
  • Mitochondria / immunology*
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Mitochondrial Proteins / biosynthesis
  • Mitochondrial Proteins / immunology
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • Neutrophils / pathology
  • Protein Transport / immunology
  • Receptors, IgE / immunology
  • Receptors, IgE / metabolism
  • bcl-2-Associated X Protein / immunology
  • bcl-2-Associated X Protein / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • BAX protein, human
  • DIABLO protein, human
  • Intracellular Signaling Peptides and Proteins
  • Mitochondrial Proteins
  • Receptors, IgE
  • bcl-2-Associated X Protein
  • Immunoglobulin E
  • Caspase 3