title: The zymogen granule protein 2 (GP2) binds to scavenger receptor expressed on endothelial cells I (SREC-I).
abstract: The pancreatic zymogen granule membrane protein (GP2) is expressed by pancreatic acinar cells and M cells of the ileum. GP2 is the closest related homologue of the urine resident Tamm-Horsfall protein (THP). Recently, it was shown that THP is a ligand of various scavenger receptors (SRs). Therefore, we were interested, if GP2 has similar properties. cDNA of different SRs was stably transfected into a murine thymoma cell line. GP2 was recombinantly expressed, purified and biotinylated. Binding or uptake of GP2 by transfected cells or monocyte-derived dendritic cells (moDCs) was analyzed by flow-cytometry. GP2 is a binding partner of the scavenger receptor expressed on endothelial cells I (SREC-I) but not of SR-AI and SR-BI. The dissociation constant (K(d)) of GP2 binding to SREC-I is 41.3nM. SREC transfected cells are able to internalize GP2. moDCs express SREC-I and also bind and internalize GP2. Inhibition of SREC-I on moDCs with anti-SREC-I antibodies does not result in a decreased GP2 binding. Interaction of GP2 with SREC-I and uptake might have profound effects in antigen clearance and mediation of the immune response. In addition to SREC-I other presently unknown receptors for GP2 on DCs might be involved in this process.
authors.affiliation: Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Hölzl
authors.forename: Johannes
authors.initials: J
authors.lastname: Hofer
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Kovarik
authors.forename: Dirk
authors.initials: D
authors.lastname: Roggenbuck
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhold
authors.forename: Alexander
authors.initials: A
authors.lastname: Goihl
authors.forename: Miriam
authors.initials: M
authors.lastname: Gärtner
authors.forename: Peter
authors.initials: P
authors.lastname: Steinberger
authors.forename: Gerhard J
authors.initials: GJ
authors.lastname: Zlabinger
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis / Q000276:immunology; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D051128:Scavenger Receptors, Class F / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D000906:Antibodies; C489339:GP2 protein, human; D058851:GPI-Linked Proteins; D011994:Recombinant Proteins; C495126:SCARF1 protein, human; D051128:Scavenger Receptors, Class F