title: Blockade of gC1qR/p33, a receptor for C1q, inhibits adherence of Staphylococcus aureus to the microvascular endothelium.
abstract: Endovascular infections with Staphylococcus aureus (S. aureus) are associated with high mortality. gC1qR/p33 (gC1qR), a receptor for the complement component C1q expressed on endothelial cells, interacts with protein A of S. aureus and gC1qR blockade reduces S. aureus colonization during infective endocarditis. The aim of this study was to analyze in vivo whether this observation is due to a decreased interaction of S. aureus with the microvascular endothelium. A dorsal skinfold chamber was prepared in Syrian golden hamsters, which were treated with the monoclonal antibody (MAb) 74.5.2 directed against gC1qR or vehicle. The interaction of fluorescein isothiocyanate (FITC)-labeled staphylococci and leukocytes with the endothelium was analyzed under physiological conditions as well as after TNF-α-induced inflammation using intravital fluorescence microscopy. Administration of MAb 74.5.2 significantly reduced adherence of S. aureus to the endothelium in untreated and TNF-α-exposed tissue. In addition, we could demonstrate in vitro that S. aureus adherence to human endothelial cells was inhibited by MAb 74.5.2. Blockade of gC1qR did not affect leukocyte-endothelial cell interaction. In conclusion, our findings indicate that immunological inhibition of gC1qR may be therapeutically used to decrease the interaction of S. aureus with the microvascular endothelium.
authors.affiliation: Institute for Medical Microbiology and Hygiene, University of Saarland, Homburg/Saar, Germany.
authors.forename: Shneh
authors.initials: S
authors.lastname: Sethi
authors.forename: Mathias
authors.initials: M
authors.lastname: Herrmann
authors.forename: Jonas
authors.initials: J
authors.lastname: Roller
authors.forename: Lutz
authors.initials: L
authors.lastname: von Müller
authors.forename: Ellinor I
authors.initials: EI
authors.lastname: Peerschke
authors.forename: Berhane
authors.initials: B
authors.lastname: Ghebrehiwet
authors.forename: Irma
authors.initials: I
authors.lastname: Bajric
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Laschke
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D006224:Cricetinae; D062109:Dermatologic Surgical Procedures; D042783:Endothelial Cells / Q000187:drug effects / Q000382:microbiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000382:microbiology*; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000382:microbiology / Q000473:pathology; D036904:Leukocyte Rolling / Q000187:drug effects; D007962:Leukocytes / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism*; D008647:Mesocricetus; D008856:Microscopy, Fluorescence; D055806:Microvessels / Q000187:drug effects / Q000382:microbiology*; D011951:Receptors, Complement / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000098:blood supply; D013194:Staining and Labeling; D013211:Staphylococcus aureus / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D011951:Receptors, Complement; D014409:Tumor Necrosis Factor-alpha; C032402:complement 1q receptor; D016650:Fluorescein-5-isothiocyanate