EGF Receptor-Dependent Mechanism May be Involved in the Tamm–Horsfall Glycoprotein-Enhanced PMN Phagocytosis via Activating Rho Family and MAPK Signaling Pathway

Molecules

Ko-Jen Li¹  Sue-Cien Siao³  Cheng-Han Wu⁵  Chieh-Yu Shen⁵  Tsai-Hung Wu⁴  Chang-Youh Tsai⁶  Song-Chou Hsieh² 

[1] Institute of Clinical Medicine, National Yang-Ming University College of Medicine, Taipei 11221, Taiwan; E-Mail:;Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan; E-Mail:;Institute of Molecular Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan; E-Mail:;Section of Nephrology, Taipei Veterans General Hospital, Taipei 11221, Taiwan; E-Mail:;Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan; E-Mails:;Section of Allergy, Immunology & Rheumatology, Taipei Veterans General Hospital, Taipei 11221, Taiwan; E-Mail:

关键词: Tamm-Horsfall glycoprotein;    phagocytosis;    EGF-like domains;    Rho family;    MAP kinase;   

DOI  :  10.3390/molecules19011328

来源: mdpi

【 摘 要 】

Our previous studies showed that urinary Tamm–Horsfall glycoprotein (THP) potently enhanced polymorphonuclear neutrophil (PMN) phagocytosis. However, the domain structure(s), signaling pathway and the intracellular events responsible for THP-enhanced PMN phagocytosis remain to be elucidated. THP was purified from normal human urine. The human promyelocytic leukemia cell line HL-60 was induced to differentiate into PMNs by all-trans retinoid acid. Pretreatment with different MAPK and PI3K inhibitors was used to delineate signaling pathways in THP-enhanced PMN phagocytosis. Phosphorylation of molecules responsible for PMN phagocytosis induced by bacterial lipopolysaccharide (LPS), THP, or human recombinant epidermal growth factor (EGF) was evaluated by western blot. A p38 MAPK inhibitor, SB203580, effectively inhibited both spontaneous and LPS- and THP-induced PMN phagocytosis. Both THP and LPS enhanced the expression of the Rho family proteins Cdc42 and Rac that may lead to F-actin re-arrangement. Further studies suggested that THP and EGF enhance PMN and differentiated HL-60 cell phagocytosis in a similar pattern. Furthermore, the EGF receptor inhibitor GW2974 significantly suppressed THP- and EGF-enhanced PMN phagocytosis and p38 and ERK1/2 phosphorylation in differentiated HL-60 cells. We conclude that EGF receptor-dependent signaling may be involved in THP-enhanced PMN phagocytosis by activating Rho family and MAP kinase.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.