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: Shneh Sethi, Mathias Herrmann, Jonas Roller, Lutz von Müller, Ellinor I Peerschke, Berhane Ghebrehiwet, Irma Bajric, Michael D Menger, Matthias W Laschke
• Journal: Microvascular research (Microvasc Res) Vol. 82 Issue 1 Pg. 66-72 (Jul 2011) ISSN: 1095-9319 [Electronic] United States
• PMID: 21539847 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Membrane Glycoproteins
• Receptors, Complement
• Tumor Necrosis Factor-alpha
• complement 1q receptor
• Fluorescein-5-isothiocyanate

Topics

• Animals
• Antibodies, Monoclonal (blood, pharmacology)
• Cell Adhesion (drug effects, physiology)
• Cell Line
• Cricetinae
• Dermatologic Surgical Procedures
• Endothelial Cells (drug effects, microbiology)
• Endothelium, Vascular (drug effects, microbiology)
• Fluorescein-5-isothiocyanate (chemistry)
• Humans
• Inflammation (chemically induced, microbiology, pathology)
• Leukocyte Rolling (drug effects)
• Leukocytes (pathology)
• Male
• Membrane Glycoproteins (antagonists & inhibitors, immunology, metabolism)
• Mesocricetus
• Microscopy, Fluorescence
• Microvessels (drug effects, microbiology)
• Receptors, Complement (antagonists & inhibitors, immunology, metabolism)
• Regional Blood Flow (drug effects, physiology)
• Skin (blood supply)
• Staining and Labeling
• Staphylococcus aureus (cytology)
• Tumor Necrosis Factor-alpha (pharmacology)