Hepatocyte growth factor attenuates eotaxin and PGD₂-induced chemotaxis of human eosinophils

• Published in: Allergy Vol. 62; no. 4; pp. 415 - 422
• Main Authors: Ito, W, Chiba, T, Kanehiro, A, Kato, H, Yamaguchi, K, Ueki, S, Kayaba, H, Chihara, J
• Format: Journal Article
• Language: English
• Published: Oxford Oxford, UK : Blackwell Publishing Ltd 01-04-2007; Blackwell
• Subjects: Allergic diseases; asthma; Biological and medical sciences; Calcium - metabolism; Cells, Cultured; Chemokine CCL11; Chemokines, CC; chemotaxis; Chemotaxis - drug effects; eosinophil; Eosinophilia - immunology; Eosinophilia - metabolism; Eosinophils - drug effects; Eosinophils - immunology; Eosinophils - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; hepatocyte growth factor; Hepatocyte Growth Factor - pharmacology; Humans; Immunopathology; Medical sciences; Prostaglandin D2; Receptors, CCR3; Receptors, Chemokine - metabolism; Receptors, Immunologic - metabolism; Receptors, Prostaglandin - metabolism; Recombinant Proteins - pharmacology; Human; Immunopathology; Lung disease; Allergy; Respiratory disease; Hepatocyte growth factor; Granulocyte; Chemotaxis; Eosinophil; Eotaxin; Asthma; Chemokine; Immunology; Bronchus disease; Obstructive pulmonary disease
• ISSN: 0105-4538; 1398-9995; 0108-1675
• DOI: 10.1111/j.1398-9995.2006.01299.x

Hepatocyte growth factor (HGF) is known to influence a number of cell types, and regulate various biologic activities including cell migration, proliferation, and survival. In a recent study, we found that, in vivo, HGF suppresses allergic airway inflammation, i.e. the infiltration of inflammatory cells including eosinophils into the airway, and further, that HGF reduces Th2 cytokine levels; however, the directly physiologic role of HGF with eosinophils remains unclear. In this study, we investigate the potential of recombinant HGF to regulate the factor-induced chemotaxis of human eosinophils. Eosinophils were isolated from subjects with mild eosinophilia by modified CD16-negative selection. After culture with or without recombinant HGF, esoinophil chemotaxis was measured by Boyden chamber and KK chamber. Treatment with HGF prevented eotaxin or prostaglandin D₂ (PGD₂)-induced chemotaxis of eosinophils. Moreover, we demonstrated that extracellular signal-regulated kinase (ERK) 1/2 and p38 mitogen-activated protein kinases as well as the enhancement of Ca²⁺ influx, which are indispensable for eosinophil chemotaxis, were attenuated by HGF treatment. Taken together, these data suggest that in allergic diseases, HGF not only mediates eosinophils through the inhibition of Th2 cytokines, but also regulates the function of eosinophils directly, provides further insight into the cellular and molecular pathogenesis of allergic reactions.