Release of soluble ICAM-5, a neuronal adhesion molecule, in acute encephalitis.

ABSTRACT

BACKGROUND: Intercellular adhesion molecule (ICAM)-5 (telencephalin) is an adhesion molecule in telencephalic neurons of the mammalian brain that binds to the leukocyte integrin CD11a/CD18. The authors observed that human cerebral neurons also expressed ICAM-5 and that ICAM-5--mediated neuron--leukocyte binding in cultured hippocampal neurons. This led the authors to examine ICAM-5 expression during clinical CNS inflammation. METHODS: The authors found, by immunoblotting, a 115-kDa soluble form of ICAM-5 (sICAM-5) cleaved from the membrane-bound (130 kDa) ICAM-5, and established an ELISA assay to measure it. CSF samples of patients with acute encephalitis and MS were studied. RESULTS: sICAM-5 was increased in encephalitis (320 plus minus 107 ng/mL; n = 25), as compared with patients with MS (128 plus minus 10 ng/mL; n = 16) and control subjects without CNS disease (137 plus minus 6 ng/mL; n = 42) (p < 0.001). The concentration of sICAM-5 correlated with the performance in the immediate recall task (p = 0.013) and with the leukocyte count in the CSF (p = 0.02), especially in cases caused by herpes simplex virus (HSV) (r = 0.94; p = 0.002). CONCLUSIONS: sICAM-5 is cleaved from CNS into CSF during acute encephalitis, and it may mediate leukocyte--neuron interactions. sICAM-5 release from cerebral neurons may actively regulate immune responses and leukocyte adhesion during microbial neuroinvasion in humans during encephalitis.