carbocyanines and Arthritis

Excessive or misplaced production of ClO(-) in living systems is usually associated with many human diseases. Therefore, it is of great importance to develop an effective and sensitive method to detect ClO(-) in living systems. Herein, we designed an 808 nm excited upconversion luminescence nanosystem, composed of the Nd(3+)-sensitized core-shell upconversion nanophosphor NaYF4:30%Yb,1%Nd,0.5%Er@NaYF4:20%Nd, which serves as an energy donor, and the ClO(-)-responsive cyanine dye hCy3, which acts as an energy acceptor, for ratiometric upconversion luminescence (UCL) monitoring of ClO(-). The detection limit of ClO(-) for this nanoprobe in aqueous solution is 27 ppb and the nanoprobe was successfully used to detect the ClO(-) in the living cells by ratiometric upconversion luminescence. Importantly, the nanoprobe realized the detection of ClO(-) in a mouse model of arthritis, which produced an excess of ROS, under 808 nm irradiation in vivo. The excitation laser efficiently reduced the heating effect, compared to the commonly used 980 nm laser for upconversion systems.

Topics: Animals; Arthritis; Carbocyanines; Cell Survival; HeLa Cells; Humans; Hypochlorous Acid; Luminescent Measurements; Metal Nanoparticles; Mice; Molecular Imaging; Neodymium

Inflammation has a key role in the pathogenesis of various human diseases. The early detection, localization and monitoring of inflammation are crucial for tailoring individual therapies. However, reliable biomarkers to detect local inflammatory activities and to predict disease outcome are still missing. Alarmins, which are locally released during cellular stress, are early amplifiers of inflammation. Here, using optical molecular imaging, we demonstrate that the alarmin S100A8/S100A9 serves as a sensitive local and systemic marker for the detection of even sub-clinical disease activity in inflammatory and immunological processes like irritative and allergic contact dermatitis. In a model of collagen-induced arthritis, we use S100A8/S100A9 imaging to predict the development of disease activity. Furthermore, S100A8/S100A9 can act as a very early and sensitive biomarker in experimental leishmaniasis for phagocyte activation linked to an effective Th1-response. In conclusion, the alarmin S100A8/S100A9 is a valuable and sensitive molecular target for novel imaging approaches to monitor clinically relevant inflammatory disorders on a molecular level.

Topics: Animals; Arthritis; Biomarkers; Calgranulin A; Calgranulin B; Carbocyanines; Collagen; Dermatitis, Contact; Female; Fluorine Radioisotopes; Hypersensitivity; Inflammation; Leishmaniasis, Cutaneous; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Molecular Imaging; Phagocytes; Positron-Emission Tomography; Th1 Cells; Tomography, X-Ray Computed

Arthritic joints are ideal disease entities to be assessed via optical imaging. Here, we investigated the selective accumulation behavior of two differently sized hemicyanine optical probes in arthritic joints and its modification during glucocorticoid therapy in the course of inflammation.. The well-standardized preclinical antigen-induced arthritis (AIA) model in rats was used. The animals were divided into 3 groups: arthritic, arthritic and dexamethasone-treated, and immunized only. After intravenous coinjection of DY-752 (size, 800 Da) and DY-682-(rat) IgG (size, 150 kDa) probes, spectrally unmixed near-infrared fluorescence images were acquired and analyzed semiquantitatively. Probe organ distribution, joint swelling, blood cell counts, joint vessel density, and histological scoring of arthritis were determined.. The local joint accumulation kinetics of the DY-752 probe differed from the DY-682-IgG one. In the course of AIA, probe signaling in arthritic joints was similar between each other. Joint swelling and histological scoring were in accordance with signaling. Dexamethasone treatment of rats with AIA significantly reduced both the near-infrared fluorescence signals and severity of arthritis but did not change the joint vascular density or the uptake of the probes by phagocytes. A differential biodistribution of both probes was encountered, but such an accumulation was prevented by dexamethasone treatment.. Near-infrared fluorescence signaling in the course of AIA closely reflects the pathophysiological events of the arthritic joint and the effects of therapy independently of the molecular size of the probe. The results show the suitability of our hemicyanine probes for imaging of arthritis.

Topics: Animals; Antigens; Arthritis; Carbocyanines; Contrast Media; Dexamethasone; Female; Humans; Image Enhancement; Immunosuppressive Agents; Microscopy, Fluorescence; Molecular Weight; Rats; Rats, Inbred Lew; Reproducibility of Results; Sensitivity and Specificity; Spectroscopy, Near-Infrared; Treatment Outcome

We demonstrated previously that variables of macrophage activation are associated with the development and progression of the arthritic lesion in the model of adjuvant induced arthritis. This association was investigated further by assessing the ability of antiarthritic agents to modulate variables of macrophage activation in direct comparison to effects on the arthritic lesion. Whereas indomethacin effectively reduced hindpaw edema, it had no significant effect on Ia expression or on any measurement of activation. Prednisolone inhibited hindpaw edema and the production of interleukin-1 (IL-1) by splenic macrophages. Only methotrexate inhibited hindpaw edema and all variables of macrophage activation (PGE2 and IL-1 production, cyanine dye accumulation) as well as the influx of Ia positive macrophages into synovial tissue.

Topics: Animals; Anti-Inflammatory Agents; Arthritis; Arthritis, Experimental; Carbocyanines; Dinoprostone; Edema; Fluorescent Dyes; Foot; Hindlimb; Interleukin-1; Interleukin-2; Macrophages; Male; Methotrexate; Monocytes; Rats; Rats, Inbred Lew; Spleen