Intracellular events in anti-IgE nonreleasing human basophils.
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.
Knol
E F
EF
Central Laboratory, The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Mul
F P
FP
Kuijpers
T W
TW
Verhoeven
A J
AJ
Roos
D
D
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D001491:Basophils / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D002118:Calcium / Q000032:analysis; D002469:Cell Separation; D003600:Cytosol / Q000737:chemistry; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006636:Histamine Release / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007211:Indoles / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D012016:Reference Values
D000888:Antibodies, Anti-Idiotypic; D007211:Indoles; D007073:Immunoglobulin E; D009240:N-Formylmethionine Leucyl-Phenylalanine; C048960:indo-1; D002118:Calcium