title: NK cell-depleting anti-asialo GM1 antibody exhibits a lethal off-target effect on basophils in vivo.
abstract: NK cells are innate immune lymphocytes and play a key role in both innate and adaptive immunity. Their pivotal functions in vivo have been illustrated in mice by means of their ablation with NK cell-depleting Abs, particularly anti-asialo GM1 (ASGM1). In this study, we show that the whole population of basophils constitutively expresses ASGM1 as well as CD49b (DX5) as does the NK cell population and was ablated in vivo by anti-ASGM1 as efficiently as by a basophil-depleting anti-FcεRIα Ab. Anti-ASGM1-mediated basophil depletion was operative as for NK cell depletion in various mouse strains, irrespective of NK1 allotype and MHC H2 haplotype, including C57BL/6, BALB/c, C3H, and A/J mice. These results identified basophils as a previously unrecognized target of anti-ASGM1-mediated cell depletion and raised concern about possible contribution of basophils, rather than or in addition to NK cells, to some of phenotypes observed in anti-ASGM1-treated mice. Indeed, regardless of the presence or absence of NK cells in mice, anti-ASGM1 treatment abolished the development of IgE-mediated chronic cutaneous allergic inflammation as efficiently as did the treatment with basophil-depleting Ab. Given the fact that basophils have recently been shown to play crucial roles in a variety of immune responses, our finding of the off-target effect on basophils issues a grave warning about the use of anti-ASGM1 and underscores the need for careful interpretation of phenotypes observed in anti-ASGM1-treated mice.
authors.affiliation: Department of Immune Regulation, Tokyo Medical and Dental University Graduate School, Tokyo 113-8519, Japan.
authors.forename: Hideto
authors.initials: H
authors.lastname: Nishikado
authors.forename: Kaori
authors.initials: K
authors.lastname: Mukai
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kawano
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Minegishi
authors.forename: Hajime
authors.initials: H
authors.lastname: Karasuyama
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D001491:Basophils / Q000166:cytology / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D005677:G(M1) Ganglioside / Q000276:immunology*; D006969:Hypersensitivity, Immediate / Q000276:immunology; D039421:Integrin alpha2 / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology*; D008212:Lymphocyte Depletion; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D017455:Receptors, IgE / Q000276:immunology
chemical_list: D000906:Antibodies; D000954:Antigens, Surface; D039421:Integrin alpha2; D017455:Receptors, IgE; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside