title: Leptin enhances survival and induces migration, degranulation, and cytokine synthesis of human basophils.
abstract: Basophils are the rarest leukocytes in human blood, but they are now recognized as one of the most important immunomodulatory as well as effector cells in allergic inflammation. Leptin, a member of the IL-6 cytokine family, has metabolic effects as an adipokine, and it is also known to participate in the pathogenesis of inflammatory reactions. Because there is an epidemiologic relationship between obesity and allergy, we examined whether basophil functions are modified by leptin. We found that human basophils express leptin receptor (LepR) at both the mRNA and surface protein levels, which were upregulated by IL-33. Leptin exerted strong effects on multiple basophil functions. It induced a strong migratory response in human basophils, similar in potency to that of basophil-active chemokines. Also, leptin enhanced survival of human basophils, although its potency was less than that of IL-3. Additionally, CD63, a basophil activation marker expressed on the cell surface, was upregulated by leptin, an effect that was neutralized by blocking of LepR. Assessments of basophil degranulation and cytokine synthesis found that leptin showed a strong priming effect on human basophil degranulation in response to FcεRI aggregation and induced Th2, but not Th1, cytokine production by the cells. In summary, the present findings indicate that leptin may be a key molecule mediating the effects of adipocytes on inflammatory cells such as basophils by binding to LepR and activating the cellular functions, presumably exacerbating allergic inflammation.
authors.affiliation: Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine, Itabashi-ku, Tokyo 173-8605, Japan. fueta-tky@umin.ac.jp
authors.forename: Maho
authors.initials: M
authors.lastname: Suzukawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nagase
authors.forename: Ikuko
authors.initials: I
authors.lastname: Ogahara
authors.forename: Kaiyu
authors.initials: K
authors.lastname: Han
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tashimo
authors.forename: Akiko
authors.initials: A
authors.lastname: Shibui
authors.forename: Rikiya
authors.initials: R
authors.lastname: Koketsu
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
authors.forename: Masao
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Ken
authors.initials: K
authors.lastname: Ohta
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D001491:Basophils / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015550:Cell Degranulation / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D002469:Cell Separation; D002470:Cell Survival / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D020738:Leptin / Q000276:immunology* / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis; D054411:Receptors, Leptin / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060149:Tetraspanin 30
chemical_list: D015703:Antigens, CD; C554586:CD63 protein, human; D016207:Cytokines; D020738:Leptin; D010980:Platelet Membrane Glycoproteins; D054411:Receptors, Leptin; D060149:Tetraspanin 30