Astrocytes in multiple sclerosis lack beta-2 adrenergic receptors

Background: In MS, T cells reactive to myelin proteins can cross the blood- brain barrier and release proinflammatory cytokines, such as interferon gam ma. These can induce glial cells to express class II major histocompatibili ty complex (MHC) molecules, which are required to present myelin antigens t o the T cells in order to mount a proper autoimmune response. Both microgli a and astrocytes can function as antigen-presenting cells. In contrast to m icroglia, endogenous suppressors, including norepinephrine, regulate astroc ytic class II MHC expression. The effects of norepinephrine are mediated th rough activation of beta(2) adrenergic receptors. Objective: To investigate beta(2) adrenergic receptors in astrocytes in MS. Methods: Immunocytochemi cal techniques were applied in postmortem brain tissue from 10 patients wit h MS, three patients with a cerebral infarction, and six controls, and in s pinal cord from three patients with ALS. Results: beta(2) adrenergic recept ors were visualized on astrocytes in white matter of controls, and they wer e prominently expressed in reactive astrocytes at the boundary of cerebral infarctions and in the lateral corticospinal tract in ALS. In MS, beta(2) a drenergic receptors could neither be visualized on astrocytes in normal-app earing white matter nor in reactive astrocytes in chronic active and inacti ve plaques, whereas they were normally present on neurons. MHC class II-pos itive astrocytes were only visualized in chronic active plaques. Conclusion s: Because astrocytic beta(2) adrenergic receptors are involved in suppress ing inducibility of MHC class II molecules, we suggest that their lack of e xpression may play an important role in the induction or perpetuation of au toimmune reactions in MS.