Ewa Chelmicka-Schorr

β-Adrenergic agonists suppress chronic/relapsing experimental allergic encephalomyelitis (CREAE) in Lewis rats

Chronic/relapsing experimental allergic encephalomyelitis (CREAE) serves as an animal model for relapsing/remitting multiple sclerosis. Treatment with the beta-adrenergic agonist isoproterenol or the beta 2-adrenergic agonist terbutaline significantly suppressed both the first acute attack and the number of relapses in CREAE Lewis rats. The number of relapses was decreased even when treatment with beta-adrenergic agonist was started after the onset of the first acute attack of CREAE. beta-adrenergic receptor number was increased significantly on splenocytes from CREAE rats as compared to healthy controls or CFA-injected rats. Terbutaline treatment of CREAE rats lowered the splenocyte receptor number to normal values.

The β-adrenergic agonist isoproterenol suppresses experimental allergic encephalomyelitis in Lewis rats ☆

Treatment with the beta-adrenergic agonist isoproterenol suppresses clinical and histological experimental allergic encephalomyelitis in Lewis rats. The effect of isoproterenol treatment is greater when the drug is given from the time of immunization through the acute phase of the illness or from 8 to 14 days post-immunization than when given for the first 7 days after immunization.

β-adrenergic receptors on splenic lymphocytes from axotomized mice

Adrenergic receptors are present on lymphocytes but the extent to which their activation modulates lymphocyte function remains unclear. We studied beta-adrenergic receptors on mouse spleen lymphocytes using the antagonist 3H-dihydroalprenolol (3H-DHA) as a specific ligand. We report a significant increase in beta-receptor density in spleen lymphocytes from mice treated with 6-hydroxydopamine (6-OHDA) to destroy peripheral sympathetic nerve endings (axotomy). Mouse spleen lymphocytes were separated into T and B subpopulations on nylon wool columns or by panning. B cells from both control and axotomized mice were found to bear twice as many beta-receptors as T lymphocytes. Finally, using flow cytometry to identify cells labeled with goat anti-mouse immunoglobulin (lg), axotomized mouse spleen lymphocyte populations were shown to contain 25% fewer B cells than controls. This work demonstrates differences in beta-adrenergic receptor density on functionally distinct populations of lymphocytes. Furthermore, we show adaptive changes in receptor density on T and B lymphocytes following sympathetic denervation. Both of these observations serve to link the immune and sympathetic nervous system in a regulatory network.

Sympathectomy augments adoptively transferred experimental allergic encephalomyelitis

Adoptively transferred experimental allergic encephalomyelitis (EAE) was significantly augmented in Lewis rats with ablated sympathetic nervous system. Sympathectomy was obtained by treatment of newborn rats with 6-hydroxydopamine. Sham-injected rats were used as a control. EAE was elicited in 7-8-week-old donor Lewis rats by immunization with a suspension of guinea pig (GP) brain and spinal cord in complete Freunds adjuvant. Successful transfer of EAE was accomplished with 50 x 10(6) lymph node cells (LNC)/rat, incubated for 72 h with GP myelin basic protein. LNC were obtained from draining lymph nodes, 9 days after immunization for EAE. The severity of passively transferred EAE was significantly augmented when donor LNC obtained from normal Lewis rats immunized for EAE were injected into sympathectomized rats as compared to sham-injected rats. When LNC were obtained from sympathectomized or sham-injected donors, the disease was significantly more severe in recipients of cells from sympathectomized animals. The severity of histological lesions in the brain and spinal cord was greater in rats with passively transferred EAE which received LNC from sympathectomized donors.

Sympathetic nervous system modulates macrophage function

We have reported previously that sympathectomy augments immune responses in mice and rats. In the present study, we show that ablation of the sympathetic nervous system augments macrophage function as measured by increased TNF secretion. We also show that a factor present in the sympathetic ganglia of newborn rats, suppresses secretion of TNF by LPS-stimulated macrophages as does the beta-adrenergic agonist isoproterenol.

The effect of chemical sympathectomy on natural killer cells in mice.

The nervous system affects immune regulation. We permanently ablated the sympathetic nervous system (SNS) of CBA mice with 6-OHDA at birth. Function of splenic natural killer (NK) cells in the sympathectomized mice was equivalent to controls at 2 weeks, but rose significantly above control levels at 4 weeks. NK cell function decreased below control values thereafter. NK cell numbers paralleled these changes in NK cell function. Our data suggest that the SNS may regulate the number and function of splenic NK cells during development.

The β2-adrenergic agonist terbutaline suppresses experimental allergic neuritis in Lewis rats

Treatment of rats with experimental allergic neuritis with the beta 2-adrenergic agonist terbutaline suppresses clinical symptoms, decreases demyelination and Wallerian degeneration in peripheral nerves and improves electrophysiological parameters. Treatment is highly effective when given from the time of immunization through the acute phase of illness, when given for the first 12 days after immunization and also when given after the onset of the disease.

A novel FKRP mutation in congenital muscular dystrophy disrupts the dystrophin glycoprotein complex

Mutations in the gene encoding fukutin related protein (FKRP) produce a spectrum of disease including congenital muscular dystrophy and limb girdle muscular dystrophy. FKRP is one member of a class of molecules thought to be glycosyltransferases that mediate O-linked glycosylation. The primary target of these glycosyltransferases is thought to be dystroglycan. We now report two unrelated Mexican children with congenital muscular dystrophy who each have the identical, novel 1387A>G, N463D mutation. Muscle biopsies from these children show a reduction of alpha-dystroglycan and also show reduction of beta-dystroglycan, and alpha-, beta-, and gamma-sarcoglycan, suggesting that FKRP mutations can perturb membrane associated proteins beyond dystroglycan.

The β2-adrenergic agonist terbutaline suppresses acute passive transfer experimental autoimmune myasthenia gravis (EAMG)

Treatment of Lewis rats with the beta 2-adrenergic agonist terbutaline suppressed clinical symptoms of acute passive transfer EAMG induced with monoclonal anti-acetylcholine receptor antibody and accelerated clinical recovery in affected animals. Electrophysiological studies showed that the amplitude of the first compound muscle action potential was significantly larger in terbutaline-treated rats as compared to controls. In both groups, a comparable number of inflammatory cells at the muscle endplates was seen.

Muscle acid protease activity in amyotrophic lateral sclerosis: Correlation with clinical and pathologic features

Acid protease activity was increased in skeletal muscle of patients with ALS. The highest levels of activity were found in individuals with the clinically and histologically most affected muscle. High levels of proteolytic activity correlated with the extent of muscle atrophy, the presence of target fibers, and the overall severity of disease.