Platelet-endothelial cell interactions in murine antigen-induced arthritis.

OBJECTIVES: Growing evidence supports the substantial pathophysiological impact of platelets on the development of rheumatoid arthritis. At present there are no methods for studying these cellular mechanisms in vivo. The aim of this study was to visualize and investigate platelet-endothelial cell interaction in the knee joint of mice with antigen-induced arthritis (AiA) by means of intravital microscopy. METHODS: In 14 mice (Balbc) intravital microscopic assessment was performed on day 8 after AiA induction in two groups (controls, AiA). The severity of AiA was assessed by measuring knee joint swelling and by histological scoring. Ex vivo fluorescently labelled rolling and adherent platelets and leucocyte-endothelium interactions were investigated by intravital fluorescence microscopy. RESULTS: Swelling of the knee joint as well as histological score was significantly enhanced in arthritic animals compared with controls. In control mice intravital microscopy revealed low baseline rolling and sticking of leucocytes and fluorescently labelled platelets. AiA induced a significant increase in the fraction of rolling leucocytes (3 times) and rolling platelets (6 times) compared to the control group. Furthermore, AiA induction resulted in a significantly enhanced number of adherent leucocytes (3-fold) and adherent platelets (12-fold) in comparison with control animals. CONCLUSIONS: Platelet kinetics were directly analysed using intravital microscopy in the arthritic microcirculation in vivo for the first time. We provide the first evidence that platelets accumulate in arthritic vessels, indicating platelet activation due to AiA. Platelet recruitment and subsequent activation might play an important role in the pathogenesis of rheumatoid arthritis.

The acute phase response following implantation of triclosan-bonded vascular prostheses.

OBJECTIVE: Infection of prosthetic material is a major complication of vascular surgery. Therapy for it includes implantation of antimicrobial prostheses bonded with different antimicrobial agents. These agents may, however, induce an acute phase reaction following implantation in the host, thus compromising follow-up of the infection. It is not known whether the antimicrobial agent triclosan induces a significant acute phase reaction when bonded to vascular prostheses. METHODS: To study this, 34 adult swine weighing 20-30 kg were allotted randomly to the following groups: (1) controls with untreated prostheses, (2) control group with triclosan-bonded prostheses, (3) therapy group with untreated prostheses, local infection with Staphylococcus aureus surgical revision, and exchange with new, untreated prostheses, and (4) therapy group with untreated prostheses, local infection with S. aureus, surgical revision, and exchange with triclosan-bonded prostheses. Serum C-reactive protein (CRP) and haptoglobin values were determined during the 28-day period after surgery. The study was performed at the Institute for Surgical Research of the Ludwig Maximilian University School of Medicine in Munich. RESULTS: Normal ranges of serum CRP and haptoglobin values were 10.7+/-1.4 microg/ml and 2.5+/-0.3 mg/ml, respectively. Following implantation of untreated and triclosan-bonded vascular prostheses, significantly elevated serum CRP and haptoglobin values were observed. No significant differences between results with triclosan-bonded and untreated prostheses were observed in control or treatment groups. No correlation was found between acute phase reaction and the absence or presence of infection. CONCLUSIONS: Triclosan is the only antimicrobial agent that bonds to vascular prosthetic material without the need of a sealant. Our data indicate that vascular prosthesis implantation, whether untreated and triclosan-bonded, results in a significant acute phase reaction. No differences between antimicrobial and untreated prostheses were observed, independently of the absence or presence of infection. The antimicrobial agent itself did not induce a severe acute phase response and may, therefore, be used in patients at risk of infection.