EGF receptor-dependent mechanism may be involved in the Tamm-Horsfall glycoprotein-enhanced PMN phagocytosis via activating Rho family and MAPK signaling pathway.
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.
Institute of Clinical Medicine, National Yang-Ming University College of Medicine, Taipei 11221, Taiwan. dtmed170@yahoo.com.tw.
Ko-Jen
KJ
Li
Institute of Molecular Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan. syuecian@gmail.com.
Sue-Cien
SC
Siao
Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan. chenghanwu@ntu.edu.tw.
Cheng-Han
CH
Wu
Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan. tsichhl@gmail.com.
Chieh-Yu
CY
Shen
Section of Nephrology, Taipei Veterans General Hospital, Taipei 11221, Taiwan. wuth@vghtpe.gov.tw.
Tsai-Hung
TH
Wu
Section of Allergy, Immunology & Rheumatology, Taipei Veterans General Hospital, Taipei 11221, Taiwan. cytsai@vghtpe.gov.tw.
Chang-Youh
CY
Tsai
Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan. hsiehsc@ntu.edu.tw.
Song-Chou
SC
Hsieh
Institute of Molecular Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan. chialiyu@ntu.edu.tw.
Chia-Li
CL
Yu
D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D058949:Uromodulin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D008070:Lipopolysaccharides; D058949:Uromodulin; D066246:ErbB Receptors; D048051:p38 Mitogen-Activated Protein Kinases; D020741:rho GTP-Binding Proteins