Intracellular events in anti-IgE nonreleasing human basophils

J Allergy Clin Immunol. 1992 Jul;90(1):92-103. doi: 10.1016/s0091-6749(06)80015-1.

Abstract

Histamine release (HR) after activation of human basophils with anti-IgE demonstrates a great variability among different donors. To elucidate the biochemical basis of this phenomenon, we studied the activation of purified basophils from donors that barely demonstrated HR (less than 7%) after stimulation by anti-IgE, although IgE was present on these cells and formyl-methionyl-leucyl-phenylalanine (fMLP)-induced HR was normal. Basophils from anti-IgE "nonreleasers" demonstrated, in contrast to cells from "releasers," hardly any changes in cytosolic-free Ca++ concentration after addition of anti-IgE. However, anti-IgE treatment of basophils from these anti-IgE nonreleasers resulted in at least two intracellular changes. First, a profound inhibition (54.2% +/- 4.2%) of a subsequent fMLP-induced HR was observed. This inhibition caused by anti-IgE was also observed in basophils from anti-IgE releasers treated with wortmannin, an inhibitor of the anti-IgE-induced HR. The time course of the inhibition induced by wortmannin plus anti-IgE on the fMLP-induced HR (half-life maximum, 4 minutes; time of maximum concentration, 10 minutes) was comparable to the time course of the anti-IgE-induced HR. Second, anti-IgE did induce homotypic aggregation in these anti-IgE-nonreleasing basophils, like in anti-IgE-releasing basophils. These studies indicate that basophils not responding to anti-IgE with HR or cytosolic-free Ca++ concentration changes do generate intracellular signals that inhibit the subsequent response to a heterologous stimulus and induce homotypic aggregation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Anti-Idiotypic / immunology*
  • Basophils / chemistry
  • Basophils / drug effects
  • Basophils / immunology*
  • Calcium / analysis
  • Cell Separation
  • Cytosol / chemistry
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Histamine Release / drug effects
  • Histamine Release / immunology*
  • Humans
  • Immunoglobulin E / immunology*
  • Indoles / pharmacology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Reference Values

Substances

  • Antibodies, Anti-Idiotypic
  • Indoles
  • Immunoglobulin E
  • N-Formylmethionine Leucyl-Phenylalanine
  • indo-1
  • Calcium