title: Depletion of eosinophils in mice through the use of antibodies specific for C-C chemokine receptor 3 (CCR3).
abstract: We have generated rat monoclonal antibodies specific for the mouse eotaxin receptor, C-C chemokine receptor 3 (CCR3). Several anti-CCR3 mAbs proved to be useful for in vivo depletion of CCR3-expressing cells and immunofluorescent staining. In vivo CCR3 mAbs of the IgG2b isotype substantially depleted blood eosinophil levels in Nippostrongyus brasiliensis-infected mice. Repeated anti-CCR3 mAb treatment in these mice significantly reduced tissue eosinophilia in the lung tissue and bronchoalveolar lavage fluid. Flow cytometry revealed that mCCR3 was expressed on eosinophils but not on stem cells, dendritic cells, or cells from the thymus, lymph node, or spleen of normal mice. Unlike human Th2 cells, mouse Th2 cells did not express detectable levels of CCR3 nor did they give a measurable response to eotaxin. None of the mAbs were antagonists or agonists of CCR3 calcium mobilization. To our knowledge, the antibodies described here are the first mAbs reported to be specific for mouse eosinophils and to be readily applicable for the detection, isolation, and in vivo depletion of eosinophils.
authors.affiliation: DNAX Research Institute of Molecular & Cellular Biology, Palo Alto, California, USA. grim@gene.com
authors.forename: J C
authors.initials: JC
authors.lastname: Grimaldi
authors.forename: N X
authors.initials: NX
authors.lastname: Yu
authors.forename: G
authors.initials: G
authors.lastname: Grunig
authors.forename: B W
authors.initials: BW
authors.lastname: Seymour
authors.forename: F
authors.initials: F
authors.lastname: Cottrez
authors.forename: D S
authors.initials: DS
authors.lastname: Robinson
authors.forename: N
authors.initials: N
authors.lastname: Hosken
authors.forename: W G
authors.initials: WG
authors.lastname: Ferlin
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.forename: H
authors.initials: H
authors.lastname: Soto
authors.forename: A
authors.initials: A
authors.lastname: O'Garra
authors.forename: M C
authors.initials: MC
authors.lastname: Howard
authors.forename: R L
authors.initials: RL
authors.lastname: Coffman
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000917:Antibody Formation; D000918:Antibody Specificity; D001992:Bronchoalveolar Lavage Fluid / Q000469:parasitology; D018076:DNA, Complementary / Q000096:biosynthesis; D004195:Disease Models, Animal; D004804:Eosinophils / Q000166:cytology*; D018604:Epitope Mapping; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008168:Lung / Q000469:parasitology; D051379:Mice; D008969:Molecular Sequence Data; D009559:Nippostrongylus; D051381:Rats; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology*; D017206:Strongylida Infections; D018418:Th2 Cells / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; C515350:CCR3 protein, human; C515351:Ccr3 protein, mouse; C515352:Ccr3 protein, rat; D018076:DNA, Complementary; D054397:Receptors, CCR3; D019707:Receptors, Chemokine