Inhibition of lymphangiogenesis and lymphatic drainage via VEGFR-3 blockade increases the severity of inflammation in chronic inflammatory arthritis
Identifieur interne : 006236 ( Main/Exploration ); précédent : 006235; suivant : 006237Inhibition of lymphangiogenesis and lymphatic drainage via VEGFR-3 blockade increases the severity of inflammation in chronic inflammatory arthritis
Auteurs : Ruolin Guo [États-Unis] ; Quan Zhou [États-Unis] ; Steven T. Proulx [États-Unis] ; Ronald Wood [États-Unis] ; Rui-Cheng Ji [Japon] ; Christopher T. Ritchlin [États-Unis] ; Bronislaw Pytowski [États-Unis] ; Zhenping Zhu [États-Unis] ; Yong-Jun Wang [République populaire de Chine] ; Edward M. Schwarz [États-Unis] ; Lianping Xing [États-Unis]Source :
- Arthritis and rheumatism [ 0004-3591 ] ; 2009.
Abstract
Investigation of the effect of lymphatic inhibition on joint and draining lymph node pathology during the course of arthritis progression in mice.
TNF transgenic (TNF-Tg) mice were used as a model of chronic inflammatory arthritis. Mice received contrast enhanced MRI to obtain ankle and knee joint synovial volumes and draining popliteal lymph node (PLN) volumes before and 8 weeks after treatment with VEGFR-3 or VEGFR-2 neutralizing antibodies, or isotype IgG. The animals were subjected to near-infrared lymphatic imaging to determine the effect of VEGFR-3 neutralization on lymph transport from paws to draining PLNs prior to sacrifice. Lymphatic vessel formation and morphology of joints and PLNs were examined by histology, immunohistochemistry, and RT-PCR.
Compared to IgG treatment, VEGFR-3 neutralizing antibody treatment significantly decreased the size of PLNs, the number of lymphatic vessels in joints and PLNs, the lymphatic drainage from paws to PLNs, and the number of VEGF-C expressing CD11b+ myeloid cells in PLNs. However, it increased the synovial volumes and inflammatory area in ankle and knee joints. VEGFR-2 neutralizing antibody, in contrast, inhibited both lymphangiogenesis and joint inflammation.
Lymphangiogenesis and lymphatic drainage are reciprocally related to the severity of joint lesions during the development of chronic arthritis. Lymphatic drainage plays a beneficial role in controlling the progression of chronic inflammation.
Url:
DOI: 10.1002/art.24764
PubMed: 19714652
PubMed Central: 2810533
Affiliations:
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<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Object</title>
<p id="P1">Investigation of the effect of lymphatic inhibition on joint and draining lymph node pathology during the course of arthritis progression in mice.</p>
</sec>
<sec sec-type="methods" id="S2"><title>Method</title>
<p id="P2">TNF transgenic (TNF-Tg) mice were used as a model of chronic inflammatory arthritis. Mice received contrast enhanced MRI to obtain ankle and knee joint synovial volumes and draining popliteal lymph node (PLN) volumes before and 8 weeks after treatment with VEGFR-3 or VEGFR-2 neutralizing antibodies, or isotype IgG. The animals were subjected to near-infrared lymphatic imaging to determine the effect of VEGFR-3 neutralization on lymph transport from paws to draining PLNs prior to sacrifice. Lymphatic vessel formation and morphology of joints and PLNs were examined by histology, immunohistochemistry, and RT-PCR.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">Compared to IgG treatment, VEGFR-3 neutralizing antibody treatment significantly decreased the size of PLNs, the number of lymphatic vessels in joints and PLNs, the lymphatic drainage from paws to PLNs, and the number of VEGF-C expressing CD11b+ myeloid cells in PLNs. However, it increased the synovial volumes and inflammatory area in ankle and knee joints. VEGFR-2 neutralizing antibody, in contrast, inhibited both lymphangiogenesis and joint inflammation.</p>
</sec>
<sec id="S4"><title>Conclusion</title>
<p id="P4">Lymphangiogenesis and lymphatic drainage are reciprocally related to the severity of joint lesions during the development of chronic arthritis. Lymphatic drainage plays a beneficial role in controlling the progression of chronic inflammation.</p>
</sec>
</div>
</front>
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