Antibodies to the junctional adhesion molecule cause disruption of endothelial cells and do not prevent leukocyte influx into the meninges after viral or bacterial infection

A hallmark of infectious meningitis is the invasion of leukocytes into the subarachnoid space. In experimental meningitis triggered by tumor necrosis factor-alpha and interleukin-1 beta, the interaction of leukocytes with end othelial cells and the subsequent migration of the cells through the vessel wall can be inhibited by an antibody to the junctional adhesion molecule ( JAM), In contrast to the cytokine-induced meningitis model, anti-JAM antibo dies failed to prevent leukocyte influx into the central nervous system aft er infection of mice with Listeria monocytogenes or lymphocytic choriomenin gitis virus. Furthermore, in bacterial meningitis, anti-JAM IgG antibodies, but not Fab fragments, caused disruption of the endothelium, Likewise comp lement-dependent antibody-mediated cytotoxicity was observed in cultured br ain endothelial cells treated with anti-JAM IgG but not with its Fab fragme nt.