Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose:
Inflammation in the rheumatoid arthritis (RA) synovium is directly associated with inflammatory cell migration across microvasculature endothelial cells (ECs), and their persistence within the synovium.
It has been shown that lymphatic vessel chemokine presentation increases in RA and so should increase the removal of the interstitial fluid containing the invading inflammatory cells which are at significant levels within the fluid. However, dysregulation of chemokine presentation between RA blood vessel and lymphatic vessel ECs may lead to reductions in removal of the ever increasing joint interstitial fluid and persistance of the inflammatory cells.
Methods: Immunohistochemistry was performed on human synovial tissue to using the pan-endothelial cell marker von-Willebrand factor, and the lymphatic EC marker LYVE-1 to assess the presence of CCL7, CCL14, CCL16 and CCL22.The number of vessels positive for each marker and the chemokine were counted to a maximum if 15 vessels over three fields of view (FOV) from 8 RA and 6 on-RA samples. Transmigration of mononuclear cells isolated from RA blood was performed over confluent human dermal lymphatic EC (HDLEC) monolayers in response to human CCL7 and analysed by FACS analysis. Inflammatory conditions were stimulated by activating overnight with 100ng/mL 100ng/mL TNF-α with 100ng/mL IFN-γ
Results: Significant increases in CCL14 and CCL22 were obsereved in RA blood vessel ECs compared to non-RA ECs (P=0.0041 and 0.014 respectively). A significant decrease in CCL7 in RA lymphatic ECs compared to non-RA| lymphatic ECs was observed (p = 0.011). Furthermore, significant increases in RA monocyte migration were observed in response to CCL7 (p = 0.002). The greatest increase to be at 250ng/ml CCL7 (p = 0.013) with a significant increase in monocyte migration also seen at 100ng/ml CCL7 (p = 0.037) compared to 0ng/ml.
Conclusion: The significant decrease of CCL7 in lymphatic ECs, combined with it having the greatest chemotactic ability for monocytes for the tested chemokines suggests CCL7 may be of importance in lymphatic removal of infiltrates in the inflamed RA synovium. Reduction in CCL7 may therefore be functional in leukocyte persistence and accumulation in the RA synovium.
Disclosure:
L. Rump-Goodrich,
None;
A. Askari,
None;
D. Mattey,
None;
J. Middleton,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/dysregulation-of-cc-chemokines-at-microvascular-endothelial-cells-of-blood-and-lymphatic-vessels-under-inflammatory-conditions/