Borrelia burgdorferi and other bacterial products induce expression and release of the urokinase receptor (CD87).
The urokinase-type plasminogen activator receptor (uPAR, CD87) is a highly glycosylated 55- to 60-kDa protein anchored to the cell membrane through a glycosylphosphatidylinositol moiety that promotes the acquisition of plasmin on the surface of cells and subsequent cell movement and migration by binding urokinase-type plasminogen activator. uPAR also occurs in a soluble form in body fluids and tumor extracts, and both membrane and soluble uPAR are overexpressed in patients with tumors. uPAR may be a factor in inflammatory disorders as well. We investigated whether Borrelia burgdorferi could stimulate up-regulation of cell membrane uPAR in vitro. B. burgdorferi, purified native outer surface protein A, and a synthetic outer surface protein A hexalipopeptide stimulated human monocytes to up-regulate membrane uPAR as measured by immunofluorescence/FACS and Western blot. The presence of soluble uPAR in culture supernatants, measured by Ag capture ELISA, was also observed. LPS from Salmonella typhimurium and lipotechoic acid from Streptococcus pyogenes also induced the up-regulation of both membrane and soluble uPAR protein by monocytes. Up-regulation of uPAR was induced by conditioned medium from B. burgdorferi/monocyte cocultures. The up-regulation of uPAR by B. burgdorferi was concomitant with an increase in uPAR mRNA, indicating that synthesis was de novo. The expression and release of uPAR in response to B. burgdorferi and other bacterial components suggests a role in the pathogenesis of Lyme disease as well as in other bacterial infections.
Coleman
J L
JL
State of New York Department of Health, State University of New York, Stony Brook, NY 11794-5120, USA. jcoleman@notes.cc.sunysb.edu
Gebbia
J A
JA
Benach
J L
JL
D000818:Animals; D000954:Antigens, Surface / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000494:pharmacology; D001428:Bacterial Vaccines; D015748:Borrelia burgdorferi Group / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D002462:Cell Membrane / Q000378:metabolism / Q000382:microbiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008074:Lipoproteins; D022123:Lyme Disease Vaccines / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D010960:Plasminogen Activators / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000096:biosynthesis / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D012486:Salmonella typhimurium / Q000276:immunology; D012995:Solubility; D013297:Streptococcus pyogenes / Q000276:immunology; D013682:Teichoic Acids / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology; D020298:U937 Cells; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D017077:Culture Media, Conditioned; D008070:Lipopolysaccharides; D008074:Lipoproteins; D022123:Lyme Disease Vaccines; C072045:OspA protein; C524898:PLAUR protein, human; C524899:Plaur protein, mouse; D020033:Protein Isoforms; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D013682:Teichoic Acids; C009900:lipoteichoic acid; D010960:Plasminogen Activators