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Molecules 2011, 16(3), 2119-2134; doi:10.3390/molecules16032119
Article

Tamm-Horsfall Glycoprotein Enhances PMN Phagocytosis by Binding to Cell Surface-Expressed Lactoferrin and Cathepsin G That Activates MAP Kinase Pathway

1, 2, 2, 2, 3, 4 and 1,2,*
Received: 7 December 2010; in revised form: 15 February 2011 / Accepted: 28 February 2011 / Published: 3 March 2011
(This article belongs to the Special Issue Glycosides)
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Abstract: The molecular basis of polymorphonuclear neutrophil (PMN) phagocytosis-enhancing activity (PEA) by human purified urinary Tamm-Horsfall glyco- protein (THP) has not been elucidated. In this study, we found human THP bound to lactoferrin (LF) and cathepsin G (CG) expressed on the surface of PMN, identified by a proteomic study with MALDI-TOF- LC/LC/mass spectrometric analysis. Pre-incubation of 10% SDS-PAGE electrophoresed PMN lysates with monoclonal anti-LF or anti-CG antibody reduced the binding with THP. To elucidate the signaling pathway of THP on PMN activation, we found THP enhanced ERK1/2 phosphorylation, reduced p38 MAP kinase phosphorylation, but had no effect on DNA binding of the five NF-kB family members in PMN. To further clarify whether the carbohydrate-side chains or protein-core structure in THP molecule is responsible for THP-PEA, THP was cleaved by different degrading enzymes with carbohydrate specificity (neuraminidase and β-galactosidase), protein specificity (V8 protease and proteinase K) or glycoconjugate specificity (carboxylpeptidase Y and O-sialoglycoprotein endopeptidase). We clearly demonstrated that the intact protein-core structure in THP molecule was more important for THP-PEA than carbohydrate-side chains. Putting these results together, we conclude that THP adheres to surface-expressed LF and CG on PMN and transduces signaling via the MAP kinase pathway to enhance PMN phagocytosis.
Keywords: Tamm-Horsfall glycoprotein; neutrophil phagocytosis-enhancing activity; lactoferrin; cathepsin G; protein-core structure; carbohydrate-side chain Tamm-Horsfall glycoprotein; neutrophil phagocytosis-enhancing activity; lactoferrin; cathepsin G; protein-core structure; carbohydrate-side chain
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Siao, S.-C.; Li, K.-J.; Hsieh, S.-C.; Wu, C.-H.; Lu, M.-C.; Tsai, C.-Y.; Yu, C.-L. Tamm-Horsfall Glycoprotein Enhances PMN Phagocytosis by Binding to Cell Surface-Expressed Lactoferrin and Cathepsin G That Activates MAP Kinase Pathway. Molecules 2011, 16, 2119-2134.

AMA Style

Siao S-C, Li K-J, Hsieh S-C, Wu C-H, Lu M-C, Tsai C-Y, Yu C-L. Tamm-Horsfall Glycoprotein Enhances PMN Phagocytosis by Binding to Cell Surface-Expressed Lactoferrin and Cathepsin G That Activates MAP Kinase Pathway. Molecules. 2011; 16(3):2119-2134.

Chicago/Turabian Style

Siao, Syue-Cian; Li, Ko-Jen; Hsieh, Song-Chou; Wu, Cheng-Han; Lu, Ming-Chi; Tsai, Chang-Youh; Yu, Chia-Li. 2011. "Tamm-Horsfall Glycoprotein Enhances PMN Phagocytosis by Binding to Cell Surface-Expressed Lactoferrin and Cathepsin G That Activates MAP Kinase Pathway." Molecules 16, no. 3: 2119-2134.


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