Interaction with complement receptor 1 (CD35) leads to amelioration of sepsis-triggered mortality but aggravation of arthritis during Staphylococcus aureus infection.
The aim of this study was to assess the importance of complement receptor 1 (CR1, CD35) in Staphylococcus aureus arthritis and sepsis. The murine model of haematogenously acquired septic arthritis was used, injecting toxic shock syndrome toxin 1 (TSST-1)-producing S. aureus LS-1 intravenously. CR1 was blocked using immunoglobulin G (IgG) rat antimouse CR1 monoclonal antibody (MoAb) (8C12). Evaluation of arthritis was performed clinically and histopathologically. In addition, the effect of blocking CR1 was assessed on the phagocytic activity of leucocytes and on T-cell dependent and independent inflammation. Seven days after inoculation with bacteria, 96% of CR1 MoAb-treated mice had clinical symptoms of arthritis compared with 58% of the control animals (P < 0.01). The severity of arthritis, expressed as mean arthritic index, was 2.9 +/- 0.5 and 1.4 +/- 0.5, respectively (P = 0.004). Fifteen days after bacterial inoculation, all CR1 MoAb-treated mice had severe arthritis (mean arthritic index 6.3 +/- 0.6), while only 77% of controls were affected (mean arthritic index 2.9 +/- 0.6; P = 0.002). The potential explanation of these findings is that treatment with CR1 MoAb significantly increases the polymorphonuclear cell-dependent inflammatory response as a result of enhanced vasodilatation in treated animals. We conclude that treatment with CR1 MoAb leads to amelioration of sepsis-induced mortality during S. aureus infection, possibly as a result of the increased phagocytic activity of peripheral phagocytes.
Sakiniene
E
E
Department of Rheumatology, University of Gothenburg, Gothenburg, Sweden.
Heyman
B
B
Tarkowski
A
A
D000818:Animals; D001170:Arthritis, Infectious / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D006098:Granulocytes / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D008297:Male; D051379:Mice; D010587:Phagocytosis / Q000276:immunology; D051381:Rats; D017463:Receptors, Complement 3b / Q000276:immunology*; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology / Q000401:mortality / Q000503:physiopathology; D013601:T-Lymphocytes / Q000276:immunology
D017463:Receptors, Complement 3b