Objective: To assess the expression of the cytokine-inducible endothelial leukocyte adhesion molecule E-selectin during the evolution of urate crystal-induced arthritis, using a recently described radiolabeled monoclonal antibody (MAb) imaging technique.
Methods: Monosodium urate (MSU) crystals and saline alone were injected respectively into the right (inflamed) and left (control) knees of 3 young pigs. Four hours later, 111In-labeled 1.2B6 F(ab')2 (anti-E-selectin MAb) and 125I-labeled MOPC 21 F(ab')2 (control MAb) were injected intravenously. Uptake of 1.2B6 in inflamed and control joints was assessed by scintigraphy 7 and 24 hours after intraarticular injection of MSU crystals. Immunohistochemistry studies and radioactivity counting of tissues were performed postmortem to confirm the observations from scintigraphy.
Results: MAb 1.2B6 F(ab')2 scintigraphic images of the knees revealed a significantly increased uptake in the right (inflamed) knee at 7 and 24 hours postinjection, particularly over the joint space. These in vivo images were consistent with E-selectin expression in the inflamed tissue detected by immunohistochemistry and with radioactivity counts postmortem. The synovial localization ratio (inflamed:control synovium counts) was 25.4 +/- 9.7 (mean +/- SD) for the anti-E-selectin MAb compared with 2.5 +/- 0.9 for the control MAb (P < 0.05, by paired Student's t-test).
Conclusion: E-selectin is expressed by synovial endothelium during the evolution of urate crystal-induced arthritis and can be detected noninvasively using a radiolabeled MAb. This E-selectin imaging technique has considerable potential for the noninvasive assessment of endothelial activation in arthritis and other inflammatory rheumatic diseases.