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 gamma. These can induce glial cells to express class II major histocompatibility complex (MHC) molecules, which are required to present myelin antigens to the T cells in order to mount a proper autoimmune response. Both microglia and astrocytes can function as antigen-presenting cells. In contrast to microglia, endogenous suppressors, including norepinephrine, regulate astrocytic class II MHC expression. The effects of norepinephrine are mediated through activation of P2 adrenergic receptors.


OBJECTIVE
To investigate P, adrenergic receptors in astrocytes in MS.


METHODS
Immunocytochemical techniques were applied in postmortem brain tissue from 10 patients with MS, three patients with a cerebral infarction, and six controls, and in spinal cord from three patients with ALS.


RESULTS
beta2 adrenergic receptors were visualized on astrocytes in white matter of controls, and they were prominently expressed in reactive astrocytes at the boundary of cerebral infarctions and in the lateral corticospinal tract in ALS. In MS, beta2 adrenergic receptors could neither be visualized on astrocytes in normal-appearing white matter nor in reactive astrocytes in chronic active and inactive plaques, whereas they were normally present on neurons. MHC class II-positive astrocytes were only visualized in chronic active plaques.


CONCLUSIONS
Because astrocytic beta2 adrenergic receptors are involved in suppressing inducibility of MHC class II molecules, we suggest that their lack of expression may play an important role in the induction or perpetuation of autoimmune reactions in MS.
De Keyser
J
J
Department of Neurology, Academisch Ziekenhuis Groningen, The Netherlands.
Wilczak
N
N
Leta
R
R
Streetland
C
C
D000368:Aged; D000369:Aged, 80 and over; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002102:Cadaver; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D020033:Protein Isoforms; D011943:Receptors, Adrenergic, beta