Molecules 2014, 19(1), 1328-1343; doi:10.3390/molecules19011328
Article

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

1 Institute of Clinical Medicine, National Yang-Ming University College of Medicine, Taipei 11221, Taiwan 2 Institute of Molecular Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan 3 Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan 4 Section of Nephrology, Taipei Veterans General Hospital, Taipei 11221, Taiwan 5 Section of Allergy, Immunology & Rheumatology, Taipei Veterans General Hospital, Taipei 11221, Taiwan 6 Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 3 December 2013; in revised form: 13 January 2014 / Accepted: 16 January 2014 / Published: 21 January 2014
(This article belongs to the Special Issue Oligosaccharides and Glyco-Conjugates)
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Abstract: 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.
Keywords: Tamm-Horsfall glycoprotein; phagocytosis; EGF-like domains; Rho family; MAP kinase

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MDPI and ACS Style

Li, K.-J.; Siao, S.-C.; Wu, C.-H.; Shen, C.-Y.; Wu, T.-H.; Tsai, C.-Y.; Hsieh, S.-C.; Yu, C.-L. EGF Receptor-Dependent Mechanism May be Involved in the Tamm–Horsfall Glycoprotein-Enhanced PMN Phagocytosis via Activating Rho Family and MAPK Signaling Pathway. Molecules 2014, 19, 1328-1343.

AMA Style

Li K-J, Siao S-C, Wu C-H, Shen C-Y, Wu T-H, Tsai C-Y, Hsieh S-C, Yu C-L. EGF Receptor-Dependent Mechanism May be Involved in the Tamm–Horsfall Glycoprotein-Enhanced PMN Phagocytosis via Activating Rho Family and MAPK Signaling Pathway. Molecules. 2014; 19(1):1328-1343.

Chicago/Turabian Style

Li, Ko-Jen; Siao, Sue-Cien; Wu, Cheng-Han; Shen, Chieh-Yu; Wu, Tsai-Hung; Tsai, Chang-Youh; Hsieh, Song-Chou; Yu, Chia-Li. 2014. "EGF Receptor-Dependent Mechanism May be Involved in the Tamm–Horsfall Glycoprotein-Enhanced PMN Phagocytosis via Activating Rho Family and MAPK Signaling Pathway." Molecules 19, no. 1: 1328-1343.

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