IgE-binding molecules (Mac-2/epsilon BP) expressed by human eosinophils. Implication in IgE-dependent eosinophil cytotoxicity.
Macrophage cell-surface protein 2 (Mac-2), a galactose specific S-type lectin identified in inflammatory macrophages, presents a high degree of homology with the rat IgE-binding protein (epsilon BP). In the present study, we show by different experimental approaches that human eosinophils can express Mac-2/epsilon BP. Flow cytometry analysis revealed that a large proportion of eosinophilic patients expressing binding sites for IgE on their eosinophil membrane, were able to bind anti-Mac-2 monoclonal antibody (mAb). Northern blot performed with eosinophil RNA hybridized with the human Mac-2 or epsilon BP cDNA probes revealed that eosinophils presented a unique transcript at 1.2 kb. Immunoprecipitation of eosinophil extracts with anti-Mac-2 mAb revealed the presence of a molecule of 29 kDa corresponding to Mac-2 protein, as well as one additional molecule of 15 kDa, absent from control alveolar macrophages. The function of these molecules was investigated in a radiolabeled IgE binding assay. Anti-Mac-2 mAb as well as galactose and lactose saccharides significantly inhibited the binding of radiolabeled human myeloma IgE protein to eosinophils. Moreover, the dose-dependent inhibition by anti-Mac-2 mAb of IgE-dependent eosinophil-mediated cytotoxicity towards parasite targets indicated the role of these IgE-binding molecules in the function of human eosinophils. These results suggest that in addition to transmembrane receptors, lectin-type molecules can participate in the IgE-dependent effector function of eosinophils.
Truong
M J
MJ
Centre d'Immunologie et de Biologie Parasitaire, Unité Mixte INSERM U 167--CNRS 624, Institut Pasteur, Lille, France.
Gruart
V
V
Liu
F T
FT
Prin
L
L
Capron
A
A
Capron
M
M
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D001665:Binding Sites; D003602:Cytotoxicity, Immunologic; D004804:Eosinophils / Q000737:chemistry* / Q000276:immunology; D005434:Flow Cytometry; D037502:Galectin 3; D006801:Humans; D007073:Immunoglobulin E / Q000502:physiology*; D037102:Lectins / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017455:Receptors, IgE / Q000502:physiology
D000943:Antigens, Differentiation; D037502:Galectin 3; D037102:Lectins; D012333:RNA, Messenger; D017455:Receptors, IgE; D007073:Immunoglobulin E