Human eosinophils and human high affinity IgE receptor transgenic mouse eosinophils express low levels of high affinity IgE receptor, but release IL-10 upon receptor activation.
FcepsilonRI expressed by human eosinophils is involved in IgE-mediated cytotoxicity reactions toward the parasite Schistosoma mansoni in vitro. However, because receptor expression is low on these cells, its functional role is still controversial. In this study, we have measured surface and intracellular expression of FcepsilonRI by blood eosinophils from hypereosinophilic patients and normal donors. The number of unoccupied receptors corresponded to approximately 4,500 Ab binding sites per cell, whereas 50,000 Ab binding sites per cell were detected intracellularly. Eosinophils from patients displayed significantly more unoccupied receptors than cells from normal donors. This number correlated to both serum IgE concentrations and to membrane-bound IgE. The lack of FcepsilonRI expression by mouse eosinophils has hampered further studies. To overcome this fact and experimentally confirm our findings on human eosinophils, we engineered IL-5 x hFcepsilonRIalpha double-transgenic mice, whose bone marrow, blood, spleen, and peritoneal eosinophils expressed FcepsilonRI levels similar to levels of human eosinophils, after 4 days culture with IgE in the presence of IL-5. Both human and mouse eosinophils were able to secrete IL-10 upon FcepsilonRI engagement. Thus, comparative analysis of cells from patients and from a relevant animal model allowed us to clearly demonstrate that FcepsilonRI-mediated eosinophil activation leads to IL-10 secretion. Through FcepsilonRI expression, these cells are able to contribute to both the regulation of the immune response and to its effector mechanisms.
Kayaba
H
H
Centre d'Immunologie et de Biologie Parasitaire, Unité Institut National de la Santé et de la Recherche Medicalé, Unité 547, Institut Pasteur, 1 rue du Prof. Calmette, 59019 Lille Cedex, France.
Dombrowicz
D
D
Woerly
G
G
Papin
J P
JP
Loiseau
S
S
Capron
M
M
D000818:Animals; D002478:Cells, Cultured; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D015848:Interleukin-5 / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics / Q000276:immunology*; D017455:Receptors, IgE / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D012550:Schistosoma mansoni / Q000276:immunology
D015848:Interleukin-5; D017455:Receptors, IgE; D016753:Interleukin-10