Chemokines Induce Migration & Changes In Actin Polymerization In Adult Rat Brain Microglia & Human Fetal Microglial Cell Line In Vitro
Cross AK, Woodroofe MN
J NeuroSci Res 1999 Jan 1;55(1):17-23
Sheffield Hallam University, School of Science, Division of Biomedical Sciences, England
Microglia, the resident Macrophages of the Central Nervous System, are the primary cells to respond to injury in the Brain, both in inflammation, e.g., in Multiple Sclerosis, and trauma.
Chemokines are potential mediators of Microglial cell recruitment to sites of injury; thus, the ability of Microglia to migrate in response to a number of Chemokines was assessed.
The Chemokines Monocyte ChemoAttractant protein 1, Macrophage Inflammatory Protein 1, Macrophage Inflammatory Protein 1beta, RANTES (regulated upon activation normal T-Cell expressed and secreted), InterLeukin 8, and IP-10 (Interferon inducible protein-10), induce migration and changes in the distribution of f-actin in adult rat Microglia and a human Microglial Cells line, CHME3, in vitro.
Both cell types show a significant migration response, above control levels, to all the chemokines tested in a typical dose-dependent manner. These Chemokines also induced a reorganization of the actin cytoskeleton of the cells.
This study indicates that Chemokines play an important role in the recruitment of Microglia to areas of Central Nervous System inflammation.
Distal Versus Proximal Arm Tremor In MS
Assessed By Visually Guided Tracking Tasks
Liu X, Miall RC, Aziz TZ, Palace JA, Stein JF
J Neurol NeuroSurg Psychiatry 1999 Jan;66(1):43-7
UnivLaboratory of Physiology, Oxford, UK
To compare Action Tremor (AT) during manual tracking in normal subjects and patients with Multiple Sclerosis with Tremor (MS-Tremor group) and without Tremor (MS-no Tremor group).
And, to differentiate Tremor occurring predominantly around the distal joint from that involving the proximal joints of the arm.
Subjects performed both a visually guided ramp tracking task using wrist flexion/extension and a whole arm circle tracking task using shoulder movement.
Action Tremor at the wrist or shoulder was computed as the SD of the tracking velocity.
The ratio of wrist:arm Tremor was then calculated to differentiate distal from proximal Tremor in the tested arm. Frequency spectra of the records were also examined.
During wrist tracking, AT in patients with Multiple Sclerosis contained a major frequency component at 4-5 Hz; the frequency was slightly lower during whole arm tracking.
The ratio of wrist:arm Tremor was significantly higher in the MS-Tremor group.
Of 12 tested arms, eight had Tremor significantly weighted towards the distal joint, only one towards the proximal joint, and three had a ratio inside the control range.
AT in the arms of patients with Multiple Sclerosis can be effectively differentiated into proximal or distal using these two different tracking tasks.
Despite the variability of the effects of Multiple Sclerosis, most of the AT was distal rather than proximal in this group of patients. Possibly Conduction Block along the CorticoCerebelloCortical pathways caused this distal Tremor.
van Sechel AC, Bajramovic JJ, van Stipdonk MJ, Persoon-Deen C, Geutskens SB, van Noort JM
J Immunol 1999 Jan 1;162(1):129-35
TNO Prevention and Health, Division of Immunological and Infectious Diseases,
Leiden, The Netherlands
The development of Multiple Sclerosis is most likely influenced by AutoImmune responses to Central Nervous System Myelin proteins as well as by infections with common Viruses such as EBV and Human HerpesVirus-6. However, much remains to be established on how these factors interact.
In this study, we show that upon EBV infection, human B-Cells start to express alphaB-Crystallin, a small stress protein that was identified previously as an Immunodominant Ag of CNS Myelin in Multiple Sclerosis patients.
EBV-induced expression of alphaB-Crystallin in B-Cells leads to HLA-DR-restricted presentation of the protein and to activation of proinflammatory alphaB-Crystallin-specific Th cells.
While alphaB-Crystallin is present in EBV-infected human B-Cells, the protein is absent from human Lymphoid tissues under normal conditions.
This is in sharp contrast to other stress proteins such as Heat-Shock Protein (hsp)27 and hsp60 that are ubiquitously expressed in these tissues.
In addition, the absence of alphaB-Crystallin from Lymphoid tissues in humans is unique as compared with other mammals.
All other species examined, including rodents, sheep, and primates, showed constitutive expression of alphaB-Crystallin in secondary Lymphoid tissues and sometimes even in the Thymus.
Since constitutive Lymphoid expression most likely results in Immunologic tolerance, such a state of tolerance to alphaB-Crystallin can be expected for all of these species, but not for humans.
When taken together, our data provide evidence for a novel mechanism by which common Viral infections can trigger Myelin-directed AutoImmunity in a way that is unique for humans.
A Theiler's Virus Alternatively Initiated Protein Inhibits The Generation Of H-2K-Restricted Virus-Specific Cytotoxicity
Lin X, Roos RP, Pease LR, Wettstein P, Rodriguez M
J Immunol 1999 Jan 1;162(1):17-24
Mayo Clinic, Dept of Immunology, Rochester, MN 55905, USA
In susceptible mouse strains, the wild-type Daniel's (wt-DA) strain of Theiler's Murine EncephaloMyelitis Virus induces a persistent Central Nervous System (CNS) infection with chronic DeMyelination.
The Virus is cleared from resistant mice with no resulting DeMyelination. We characterized the role of the DA L* protein in late DeMyelination and persistent infection. The DA genome has two alternative reading frames, encoding the virus polyprotein and L*, respectively.
The mutant virus DAL*-1 fails to synthesize L* and does not persist in the CNS of wt-DA-susceptible SJL/J or B10.S mice.
Since Class I-restricted CytoToxicity has been shown to determine resistance to virus persistence and DeMyelination in this model, virus-specific CytoToxicity in the CNS of DA-resistant (B6 or B10) and -susceptible (SJL/J and B10.S) mice during the acute stage of DA and DAL*-1 infection was characterized.
Following IntraCerebral inoculation with DAL*-1, virus-specific Db- and Kb-restricted CTLs were demonstrated in the CNS of resistant B10 mice, whereas only Db-restricted CTL were found in wt-DA-inoculated mice.
CTLs specific to wt-DA or DAL*-1 recognized Class I-presented peptides from either of the viruses.
Of particular interest, Ks-restricted virus-specific CytoToxicity-restricted CTLs were identified in the CNS of susceptible SJL/J (H-2s) and B10.S (H-2s) mice inoculated with DAL*-1.
In contrast, no virus-specific CTLs were identified in the CNS of SJL/J and B10.S mice inoculated with wt-DA.
We propose that L* inhibits the generation of H-2K-restricted Virus-specific CytoToxicity in the CNS, permitting a persistent infection in susceptible strains, with subsequent inflammatory DeMyelination in the CNS similar to that in human Multiple Sclerosis.