Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Aggressiveness of Rheumatoid Arthritis Synovial Fibroblasts Is Characterized by Fast Transendothelial Migratory, Invasive and Neoangiogenic Potential
Zimmermann1, Birgit, Lefevre1, Stephanie, Fischer2, Silvia, Gansler2, Julia, Lehr3, Angela, Rehart3, Stefan, Sturz2, Henning
Justus-Liebig-University of Giessen, Internal Medicine and Rheumatology. Kerckhoff-Klinik, Bad Nauheim, Germany
Justus-Liebig-University of Giessen, Giessen, Germany
Markus-Hospital, Frankfurt, Germany
In rheumatoid arthritis (RA), synovial fibroblasts (SF) are activated cells that participate in cartilage degradation and joint destruction. Recently, we demonstrated the long-distance migratory behavior of RASF and examined the early events in this process that may contribute to the spreading of the disease between joints.
In vitro transmigration assays through human umbilical vein endothelial cells (HUVECs) cultured in monolayers on rat tail collagen in transwell-chambers were performed. RASF were placed on the endothelial monolayer and the number of migrating RASFs was counted at different time points (416 h). RASF migration in vivo was investigated using the SCID mouse model of RA: 1.5×105 RASF were implanted together with healthy human cartilage in a carrier matrix at the ipsilateral site (I). Cartilage without RASF was implanted at the contralateral site (IL) of the SCID mice. Neoangiogenesis adjacent to the implated cartilage was determined (35 hours, 6, 12, 18, 24, 30 days). Implants and spleens were removed and cartilage invasion of RASF was analyzed histologically using an established scoring system. Implants and spleens were analyzed immunohistochemically with species-specific antibodies.
RASF transmigration through endothelial monolayers and collagen coating was already detectable after 4 hours (21.8%±0.2%). In all settings, the number of migrating cells increased over time. At the ipsilateral implant, invasion started at day 18 (mean invasion score: 0.86), at the contralateral site after 24 days of implantation (mean invasion score: 0.43). The invasion increased continously over time. Interestingly, RASF could be detected in all spleens of the SCID mice at every timepoint. Neoangiogenesis and vessel formation into both implants could be observed already after 35 h, which was more prominent at the ispilateral site.
Neoangiogenesis appears to be a very early event in RASF migration in the SCID mouse model for RA, which facilitates not only the rapid transmigration of RASF into the circulation and the migration to the contralateral implant but adds also to the knowledge of the pathophysiologic puzzle of spreading of human RA.
To cite this abstract, please use the following information:
Zimmermann, Birgit, Lefevre, Stephanie, Fischer, Silvia, Gansler, Julia, Lehr, Angela, Rehart, Stefan, et al; Aggressiveness of Rheumatoid Arthritis Synovial Fibroblasts Is Characterized by Fast Transendothelial Migratory, Invasive and Neoangiogenic Potential [abstract]. Arthritis Rheum 2009;60 Suppl 10 :27