Leptin‐mediated cytokine release and migration of eosinophils: Implications for immunopathophysiology of allergic inflammation

• Published in: European Journal of Immunology Vol. 37; no. 8; pp. 2337 - 2348
• Main Authors: Wong, Chun Kwok, Cheung, Phyllis F.‐Y., Lam, Christopher W. K.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01.08.2007
• Subjects: Blotting, Western; Cell Adhesion Molecules - immunology; Cell trafficking; Chemokines; Chemotaxis, Leukocyte - immunology; Cytokines; Cytokines - secretion; Enzyme Activation - immunology; Enzyme-Linked Immunosorbent Assay; Eosinophils; Eosinophils - immunology; Extracellular Signal-Regulated MAP Kinases - metabolism; Flow Cytometry; Humans; Hypersensitivity - immunology; Inflammation - immunology; Leptin - immunology; NF-kappa B - metabolism; p38 Mitogen-Activated Protein Kinases - metabolism; Signal transduction
• ISSN: 0014-2980; 1521-4141; 1365-2567
• DOI: 10.1002/eji.200636866

Leptin is a pleiotropic adipocyte‐derived cytokine used in hypothalamic regulation of body weight and modulation of immune response by stimulating T cells, macrophages and neutrophils. Leptin has been shown to be an eosinophil survival factor. We examined the immunopathological mechanisms for the activation of human eosinophils from healthy volunteers by leptin in allergic inflammation. Adhesion molecules, cytokines and cell migration were assessed by flow cytometry, ELISA and Boyden chamber assay, respectively. Intracellular signaling molecules were investigated by membrane array and Western blot. Leptin could up‐regulate cell surface expression of adhesion molecule ICAM‐1 and CD18 but suppress ICAM‐3 and L‐selectin on eosinophils. Leptin could also stimulate the chemokinesis of eosinophils, and induce the release of inflammatory cytokines IL‐1β and IL‐6, and chemokines IL‐8, growth‐related oncogene‐α and MCP‐1. We found that leptin‐mediated induction of adhesion molecules, release of cytokines and chemokines, and chemokinesis were differentially regulated by the activation of ERK, p38 MAPK and NF‐κB. In view of the above results and elevated production of leptin in patients with allergic diseases such as atopic asthma and atopic dermatitis, leptin could play crucial immunopathophysiological roles in allergic inflammation by activation of eosinophils via differential intracellular signaling cascades.