RRC ID 38602
著者 El-Shazly AE, Henket M, Lefebvre PP, Louis R.
タイトル 2B4 (CD244) is involved in eosinophil adhesion and chemotaxis, and its surface expression is increased in allergic rhinitis after challenge.
ジャーナル Int J Immunopathol Pharmacol
Abstract A role for the subtypes of CD2 Ig superfamily receptors has been recently demonstrated in eosinophilic inflammation in experimental asthma and atopic asthmatics. We investigated the functions of 2B4 (CD244) molecules in eosinophil adhesion and chemotaxis, and correlated the results to the pathophysiology of allergic rhinitis (AR). Herein, we show that agonistic stimulation of 2B4 by C1.7, the anti-human 2B4 functional grade purified antibody, resulted in significant increase of eosinophils and eosinophil cell line (Eol-1 cells) adhesion to collagen type IV, and random migration. These functions were associated with tyrosine kinase phosphorylation of several protein residues of low molecular weight. Flow cytometry (FACS) experiments demonstrated that Eol-1 cells, normal peripheral blood eosinophils and eosinophils from AR patients, express surface 2B4 molecules. In vitro AR model demonstrated that the CC-chemokine receptor CCR3 stimulation by eotaxin induced significant increase in the expression of surface 2B4 in eosinophils and Eol-1 cells. Immunofluorescence confocal microscopy images showed that eotaxin induces also redistribution of 2B4 molecules towards the pseudopods in eosinophils and Eol-1 cells, changing their shape. Blocking of 2B4 molecules by the corresponding neutralizing antibody inhibited eotaxin induced Eol-1-adhesion, chemotaxis and the cytoskeleton changes. Pretreatment of Eol-1 cells with 1 microM genistein blocked eotaxin-induced Eol-1 adhesion, chemotaxis and 2B4 up-regulated expression. In vivo correlation demonstrated the expression of 2B4 molecules in eosinophils from AR patients to be significantly increased, after nasal provocation challenge. These results identify a novel role for 2B4 molecules in eosinophil functional migratory response and may point to a novel tyrosine kinase-mediated ligation between CCR3 receptor and 2B4 co-receptor in eosinophil chemotaxis. If so, then 2B4 molecules would be a novel target for therapeutic modalities in diseases characterized by eosinophilia such as AR.
巻・号 24(4)
ページ 949-60
公開日 2011-1-1
DOI 10.1177/039463201102400413
PII 13
PMID 22230401
MeSH Actins / metabolism Animals Antibodies, Monoclonal / pharmacology Antigens, CD / metabolism* Cell Adhesion* / drug effects Cell Line Cell Membrane / drug effects Cell Membrane / immunology* Cell Shape Chemotaxis, Leukocyte* / drug effects Eosinophils / drug effects Eosinophils / immunology* Flow Cytometry Fluorescent Antibody Technique Humans Microscopy, Confocal Nasal Provocation Tests Protein Kinase Inhibitors / pharmacology Protein-Tyrosine Kinases / antagonists & inhibitors Protein-Tyrosine Kinases / metabolism Pyroglyphidae / immunology Receptors, CCR3 / immunology Receptors, Immunologic / agonists Receptors, Immunologic / antagonists & inhibitors Receptors, Immunologic / metabolism* Rhinitis, Allergic, Perennial / diagnosis Rhinitis, Allergic, Perennial / immunology* Signal Transduction Signaling Lymphocytic Activation Molecule Family
IF 2.209
引用数 12
WOS 分野 PATHOLOGY PHARMACOLOGY & PHARMACY IMMUNOLOGY
リソース情報
ヒト・動物細胞