Lack of Fc-epsilon receptors on murine eosinophils: implications for the functional significance of elevated IgE and eosinophils in parasitic infections.
Chronic infection with Schistosoma mansoni induces in humans and mice a Th2-dominant immune response in which eosinophils and IgE are conspicuously elevated. Human eosinophils express IgE receptors that participate in an IgE-dependent eosinophil-mediated ADCC reaction against Schistosomula larvae in vitro. To investigate the expression of IgE receptors on murine eosinophils, they were purified (>95% pure by Giemsa-stained cytospin preparations) from liver granulomas of Schistosoma-infected mice. Flow cytometric analysis showed the absence of the low-affinity IgE receptor Fc-epsilon RII (CD23) and Mac-2 and the absence of binding of murine IgE. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of granuloma eosinophil mRNA did not detect transcripts for Fc-epsilon RII or the alpha-chain of the high-affinity IgE receptor Fc-epsilon RI, but did detect transcripts that encode Mac-2 and the low-affinity IgG receptors Fc-gamma RIIb2, Fc-gamma RIII, and the FcR-associated gamma-chain. In vitro stimulation of granuloma eosinophils with interleukin-4 (IL-4) did not induce IgE binding, surface expression of Mac-2, or the transcription of Fc-epsilon receptors (Fc-epsilon RI, Fc-epsilon RII/CD23). To investigate normal murine eosinophils, we cultured normal mouse bone marrow cells with recombinant IL-3, recombinant IL-5, and recombinant granulocyte-macrophage colony-stimulating factor, conditions that promote eosinophil differentiation. Flow cytometric analysis of bone marrow-derived eosinophils failed to detect IgE binding or cell surface expression of Fc-epsilon RII and Mac-2, and RT-PCR analysis of fluorescence-activated cell sorted bone marrow-derived eosinophils failed to detect transcripts that encode Fc-epsilon RI or Fc-epsilon RII. These findings show that, in contrast to human eosinophils, murine eosinophils do not express cell surface receptors that bind IgE. However, because IgG receptors (Fc-gamma RIIb2, Fc-gamma RII) were present on eosinophils purified from granulomas, we investigated whether they might be involved in eosinophil activation. We found that an oxidative burst in eosinophils could be triggered through their IgG receptors.
de Andres
B
B
Department of Pathology, The University of Iowa College of Medicine, Iowa City 52242, USA.
Rakasz
E
E
Hagen
M
M
McCormik
M L
ML
Mueller
A L
AL
Elliot
D
D
Metwali
A
A
Sandor
M
M
Britigan
B E
BE
Weinstock
J V
JV
Lynch
R G
RG
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004578:Electron Spin Resonance Spectroscopy; D047209:Eosinophil Peroxidase; D004802:Eosinophilia / Q000209:etiology*; D004804:Eosinophils / Q000737:chemistry*; D005434:Flow Cytometry; D037502:Galectin 3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006099:Granuloma / Q000209:etiology / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007377:Interleukin-3 / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology; D008099:Liver / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D010544:Peroxidases / Q000032:analysis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D017455:Receptors, IgE / Q000032:analysis*; D011994:Recombinant Proteins / Q000494:pharmacology; D012555:Schistosomiasis mansoni / Q000150:complications / Q000276:immunology*
D000943:Antigens, Differentiation; D037502:Galectin 3; D007377:Interleukin-3; D015848:Interleukin-5; D012333:RNA, Messenger; D017455:Receptors, IgE; D011994:Recombinant Proteins; D007073:Immunoglobulin E; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D047209:Eosinophil Peroxidase; D010544:Peroxidases