Elevated plasma levels and monocyte-associated expression of CD137 ligand in patients with acute atherothrombotic stroke.

BACKGROUND: CD137 ligand (CD137L) is expressed by various immune cells and exists in membrane-bound and soluble forms. Recently, CD137L was found to be localized to macrophages in human atherosclerotic lesions and CD137L levels were much higher in atherosclerotic lesions than in normal arteries. However, the role of CD137L with different forms in atherothrombotic stroke remains unclear. PATIENTS AND METHODS: The soluble CD137L (sCD137L) protein and CD137L expression on monocytes were analyzed by an enzyme-linked immunosorbent assay and flow cytometry in peripheral blood of patients with acute ischemic atherosclerotic stroke, atherosclerosis controls and normal controls. RESULTS: During the initial 24h after onset, the stroke patients had elevated plasma sCD137L levels (133.2 pg/ml) and CD137L expression on monocytes [7.9 ± 4.1%, 7.0 ± 4.0 mean fluorescence intensity (MFI)] as compared with normal controls (75 pg/ml, p < 0.05; 4.6 ± 2.4%, 4.1 ± 2.7 MFI, p < 0.05). CONCLUSIONS: The dysregulation of CD137L expression may reflect a persistent chronic inflammatory response that may have been induced during early stages of the disease. Our results strongly suggest that the abnormal expression of CD137L on monocytes may lead to dyregulated CD137L/CD137 signaling and consequently form part of a positive-feedback, inflammation-promoting circuit in stroke, while the elevated sCD137L protein levels may function as a self-regulatory mechanism of CD137/CD137L interaction and costimulation.