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A Potential New Mouse Model of Axial Spondyloarthritis Involving the Complement System
Holers V. Michael,La Rosa Francisco G.,Banda Nirmal K. 대한면역학회 2021 Immune Network Vol.21 No.6
Many mouse models of rheumatoid arthritis have been identified, but only a limited number are present for axial spondyloarthritis (AxSpA). Collagen Ab-induced arthritis (CAIA) is one of the most widely used mouse models of arthritis, and it is complement-dependent. We found that mice developing CAIA also developed spinal lesions similar to those found in AxSpA. To induce CAIA, mice were injected intraperitoneally at day 0 with anti-collagen Abs, followed by LPS injection at day 3. CAIA mice demonstrated a significant kyphosis through the spine, as well as hypertrophic cartilage and osseous damage of the intravertebral joints. Immunohistochemical staining of the kyphotic area revealed increased complement C3 deposition and macrophage infiltration, with localization to the intravertebral joint margins. Near Infrared (NIR) in vivo imaging showed that anti-collagen Abs conjugated with IRDye® 800CW not only localized to cartilage surface in the joints but also to the spine in arthritic mice. We report here a novel preclinical mouse model in which, associated with the induction of CAIA, mice also exhibited salient features of AxSpA; this new experimental model of AxSpA may allow investigators to shed light on the local causal mechanisms of AxSpA bone and soft tissue changes as well as treatment.
Thurman, Joshua M.,Kraus, Damian M.,Girardi, Guillermina,Hourcade, Dennis,Kang, Hee J.,Royer, Pamela A.,Mitchell, Lynne M.,Giclas, Patricia C.,Salmon, Jane,Gilkeson, Gary,Holers, V. Michael Elsevier 2005 Molecular immunology Vol.42 No.1
<P><B>Abstract</B></P><P>Studies in gene-targeted mice have demonstrated that factor B of the alternative complement pathway plays an important role in several disease models, but an exogenous inhibitor of factor B has not previously been available. We have developed an inhibitory monoclonal antibody directed against a critical epitope on mouse factor B and have tested it in a model of antiphospholipid (aPL) antibody (Ab)-induced fetal loss. Gene-targeted factor B-deficient mice (fB<SUP>−/−</SUP>) were injected with a fusion protein comprised of the second and third short consensus repeat (SCR) domains of mouse factor B linked to a mouse IgG<SUB>1</SUB> Fc domain. Hybridomas were made from splenocytes of the immunized mouse. One mAb, designated 1379, produced an IgG<SUB>1</SUB> antibody that inhibited alternative pathway activation in vitro and in vivo by preventing formation of the C3bBb complex. Strikingly, this mAb inhibited alternative pathway activation in serum from mice, rats, humans, monkeys, pigs and horses. Fab fragments made from this mAb also inhibited alternative pathway activation. Epitope mapping demonstrated that this antibody binds to factor B within the third SCR domain. When mAb 1379 was administered to mice that also received human IgG containing antiphospholipid antibodies, it provided significant protection from antiphospholipid antibody-induced complement activation and fetal loss. Thus, this mAb to factor B has broad species reactivity and effectively inhibits alternative pathway activation. The mAb protects mice in an in vivo model of antiphospholipid antibody syndrome, demonstrating the therapeutic potential for the inhibition of factor B in this disease.</P>
Real Time Spectroelectrochemical Experiments with a Multichannel Detector
Sun-Il Mho,Sally N. Holer,Bum-Soo Kim,Su-Moon Park Korean Chemical Society 1994 Bulletin of the Korean Chemical Society Vol.15 No.9
A spectroelectrochemical system assembled with a white light source, bifurcated optical fiber, Oriel Multispec spectrograph, and a charge-coupled device (CCD) detector is described. The system is shown to be capable of acquiring a whole spectrum in the spectral range of 290-800 nm in 25 ms or a longer period during electrochemical experiments at reflective working electrodes such as platinum or mercury. The utility of the system in studying electrochemical reactions during the potential scan, galvanostatic electrolysis, or after the potential step is demonstrated.