UMLS:C0014070 - FACTA Search

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Query: UMLS:C0014070 (encephalomyelitis)
13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of a battery of adhesion-related molecules and cytokines was investigated by immunocytochemistry in the central nervous system (CNS) of SJL/J mice sensitized for experimental autoimmune encephalomyelitis (EAE). These molecules consisted of the ligands MECA-325, intercellular adhesion molecule-1, and major histocompatibility complex molecules I and II, plus the receptors lymphocyte function-associated antigen-1, CD8, and CD4. The cytokines comprised interferon-gamma and tumor necrosis factor-alpha. EAE was induced by the adoptive transfer of myelin basic protein-sensitized lymphocytes. MECA-325, a marker for murine high endothelial venules in lymph node tissue, was absent from normal CNS tissue, was expressed at low levels on venules 24 to 48 hours before the onset of clinical signs, rose to maximal levels during acute disease, decreased to preclinical levels during remissions, and rose again during relapses. Intercellular adhesion molecule-1, major histocompatibility antigen-I, and major histocompatibility antigen-II showed similar fluctuations around CNS vessels. The receptors lymphocyte function-associated antigen-1 and CD4 fluctuated in parallel with the above molecules, whereas CD8 remained at a similar low level. Interferon-gamma was present during the acute, remitting, and relapsing phases and was localized to inflammatory cells, whereas tumor necrosis factor occurred at low levels only. Thus, several molecules associated with lymphocyte traffic in lymphoid tissue are selectively expressed in a stage-specific manner within the target organ, the CNS, during EAE. This suggests that the CNS may act as an ancillary organ of the immune system, and that cellular traffic into the CNS during EAE is related to the fluctuating expression of several distinct adhesion-related molecules, frequently co-expressed on the same vessel. The findings may have relevance to the sequence of events in the developing CNS lesion of multiple sclerosis.
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PMID:Adhesion-related molecules in the central nervous system. Upregulation correlates with inflammatory cell influx during relapsing experimental autoimmune encephalomyelitis. 167 55

This study investigated the expression of intercellular adhesion molecule-1 (ICAM-1; CD54) by cells of the central nervous system (CNS) during acute experimental allergic encephalomyelitis (EAE) and chronic relapsing EAE (CREAE). In the CNS of normal guinea pigs, only a few endothelial cells expressed detectable levels of ICAM-1, whereas during the active phases of the disease ICAM-1 was present on cells of the perivascular infiltrate and the endothelia of both lesion- and non-lesion-associated blood vessels. In addition, cultured cerebrovascular endothelia maintained in 'standard' culture medium did not express ICAM-1, but they could be induced to express this antigen on incubation in a lymphocyte-conditioned medium. These findings suggest that the induction of ICAM-1 on CNS endothelia may be important in antigen presentation or in promoting lymphocyte extravasation across the blood-brain barrier in inflammatory disorders of the CNS.
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PMID:Endothelial cell expression of the intercellular adhesion molecule-1 (ICAM-1) in the central nervous system of guinea pigs during acute and chronic relapsing experimental allergic encephalomyelitis. 197 68

Adhesion molecules facilitate infiltration of leukocytes into the central nervous system (CNS) of mice with experimental allergic encephalomyelitis (EAE). Expression of the adhesion molecules ICAM-1 (CD54), VCAM-1 (CD106), L-selectin (CD62L), and leukosialin (CD43) was analyzed via immunocytochemistry 4-28 days after the injection of encephalitogen into EAE-susceptible SWXJ mice. Constitutive ICAM-1 expression on large-diameter CNS vessels was upregulated on post-injection days 8, 11, 14 and 18 (concurrent with de novo expression on smaller capillaries and glial cells), partially downregulated by day 23, and back to control levels by day 28. Constitutive VCAM-1 expression was upregulated by day 14 and back to control levels by day 28. Upregulation of ICAM-1 temporally coincided with the immigration of CD4+ lymphocytes and L-selectin+ leukocytes into the CNS, while downregulation coincided with their emigration. The infiltration of CD43+ leukocytes also coincided with the upregulation of vascular adhesion molecules, but CD43+ cells remained in the CNS after ICAM-1 and VCAM-1 had returned to control levels. Cellular infiltration and adhesion-molecule expression preceded EAE clinical symptoms by a minimum of 3 days, suggesting a causal role of adhesion molecules in the initiation of CNS inflammation. However, prophylactic injections of monoclonal antibodies against either ICAM-1, L-selectin, or CD43, did not ameliorate the clinical severity of EAE in this model.
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PMID:Expression of ICAM-1, VCAM-1, L-selectin, and leukosialin in the mouse central nervous system during the induction and remission stages of experimental allergic encephalomyelitis. 752 43

To study the mechanisms involved in the pathogenesis of the blood-brain barrier (BBB) breakdown in autoimmune demyelinating diseases, such as experimental allergic encephalomyelitis (EAE), we investigated the cell interaction in vitro between myelin basic protein (MBP)-specific encephalitogenic T cells and normal and inflamed cerebral endothelial cells, and the cytotoxic effect of antigen specific T cell lines on normal and inflamed cerebral endothelial cells. The importance of relationship between cell surface adhesion and cytotoxic T lymphocyte (CTL) was examined by monoclonal antibodies (mAb) against adhesion receptors. The adhesion of encephalitogenic T cells to inflamed endothelial cells was significantly increased as compared with normal endothelial cells (P < 0.001). The percentage lysis of inflamed endothelial target cells was significantly increased by incubation with MBP-encephalitogenic T cell lines in the presence of MBP as compared with those of normal endothelial targets (P < 0.0001). Intercellular adhesion molecule-1 (ICAM-1) is not involved in T cell adhesion to endothelial cells or cytotoxic endothelial cell lysis. Antibodies against human alpha 4 integrin (HP 2/1) and beta 1 (A11B2) inhibited T cell adhesion, but did not block cytotoxic endothelial cell lysis. These results indicate that T cell adhesion to inflamed cerebral endothelial cells and cytotoxicity of T cells for cerebral endothelial cells may play a central role in the breakdown of the BBB and development of inflammatory lesions in the central nervous system(CNS).
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PMID:Adhesion and cytotoxicity of myelin basic protein-specific encephalitogenic T cells to normal and inflamed cerebral endothelial cells. 752 2

The nature of inflammatory lymphocytes recruited to the CNS has been studied in a model of chronic inflammation. Injection of killed Corynebacterium parvum into the cortex of the mouse brain produces a circumscribed inflammatory cellular infiltrate around the injection site, and recruited mononuclear inflammatory cells (IC) can be isolated for flow cytometric analysis. The majority of IC were T cells. In comparison with the predominant naive population of mesenteric lymph node T cells, IC T cells express much higher levels of CD44, LFA-1 and ICAM-1, and lower levels of CD45RB, features commonly associated with memory (previously activated) cells. In addition, in contrast to the L-selectin+ alpha 6-integrinlow phenotype of naive lymph node T cells, IC T cells lacked L-selectin and were alpha 6-integrin-. Mac-1, recently proposed as another marker of memory T cell differentiation, was not displayed by IC T cells, suggesting that Mac-1 expression may be heterogeneous among memory T cell subsets. A subset of mesenteric lymph node (MLN) T cells, probably representing activated T cells undergoing the naive to memory transition, but not of IC T cells, expressed high levels of alpha 6-, beta 7- and alpha E-integrin. IC and MLN naive T cells expressed comparable levels of alpha 4-integrin, but IC T cells stain poorly with anti-beta 7 mAbs and with mAb DATK 32, specific for the alpha 4 beta 7 heterodimeric lymphocyte homing receptor for the mucosal addressin MAdCAM-1, suggesting that these inflammatory cells express more alpha 4 beta 1 than alpha 4 beta 7. Consistent with this, in in vitro adhesion assays, brain IC bound better than MLN cells to the alpha 4 beta 1 integrin ligand VCAM-1 and the LFA-1 ligand ICAM-1 but adhered very poorly to the alpha 4 beta 7 ligand MAdCAM-1. These findings are consistent with and extend previous immunohistological studies of T cells in murine experimental autoimmune encephalomyelitis, and demonstrate a distinctive phenotype for lymphocytes being present in the chronically inflamed brain.
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PMID:Lymphocytes infiltrating the CNS during inflammation display a distinctive phenotype and bind to VCAM-1 but not to MAdCAM-1. 754 Aug 64

We used competitive polymerase chain reaction to quantify messenger RNA for the lymphocyte antigens CD4 and CD8, the adhesion molecules ICAM-1 and VCAM-1, and the MHC class II I-A molecule in the spinal cords of SJL/J mice at multiple times during the development and resolution of experimental allergic encephalomyelitis (EAE). CD4 and CD8 were not quantifiable at baseline, became detectable at 5 days after immunization, and increased steadily to a peak during clinical disease. I-A increased after CD4 and CD8, but before onset of disease. ICAM-1 and VCAM-1 did not increase until after onset of clinical disease. CD4, CD8, and I-A remained elevated long after recovery from disease. These results suggest that infiltration of CD4 and CD8 cells into the spinal cord and subsequent upregulation of I-A mRNA play an important role in the development of EAE, but reversal of these processes is not necessary for recovery. Upregulation of ICAM-1 and VCAM-1 mRNA does not appear to be important for development of disease.
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PMID:Competitive PCR quantification of CD4, CD8, ICAM-1, VCAM-1, and MHC class II mRNA in the central nervous system during development and resolution of experimental allergic encephalomyelitis. 769 55

Intercellular adhesion molecule-1 (ICAM-1) is a cell surface glycoprotein which can be induced on astrocytes, the major glial cell of the central nervous system (CNS). In this study, we examined the effect of three proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interferon-gamma (IFN-gamma), on the expression of ICAM-1 by primary rat astrocytes. Astrocytes constitutively express ICAM-1 mRNA and protein, which is enhanced by treatment with TNF-alpha, IL-1 beta and IFN-gamma. TNF-alpha is the most potent inducer of ICAM-1 expression, followed by IL-1 beta, then IFN-gamma. Kinetic analysis demonstrated optimum ICAM-1 mRNA expression after a 1-h exposure to TNF-alpha, 2 h exposure to IL-1 beta, and 4 h exposure to IFN-gamma. Peak ICAM-1 protein expression was detected 12-16 h after treatment with TNF-alpha or IL-1 beta, and after a 24-h exposure to IFN-gamma. Nuclear run-on analysis demonstrated that the ICAM-1 gene is transcribed under basal conditions in astrocytes, and that both TNF-alpha and IL-1 beta enhance transcriptional activation of the ICAM-1 gene. ICAM-1 mRNA stability studies determined that basal ICAM-1 mRNA has a half-life of about 1 h, and that TNF-alpha, IL-1 beta and IFN-gamma have a modest effect on stabilization of basal ICAM-1 mRNA expression. These results indicate that under inflammatory conditions in the CNS, such as multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE), astrocytes can be induced to express the adhesion molecule ICAM-1, which can contribute to inflammatory events within the CNS.
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PMID:Regulation of intercellular adhesion molecule-1 gene expression by tumor necrosis factor-alpha, interleukin-1 beta, and interferon-gamma in astrocytes. 791 Jan 70

Induction of experimental allergic encephalomyelitis is facilitated in a genetically resistant BALB/c mouse strain by a nonpathogenic strain of a neurotropic alphavirus, Semliki Forest virus (SFV-A7). One possible explanation for this enhancement is virus infection of endothelial cells (EC), causing increased permeability of the blood-brain barrier. We have now sought evidence for virus infection of EC in vivo by immunocytochemistry and in situ hybridization. SFV-A7 antigens and RNA were detected in vascular EC and perivascular neurons in cerebellar and spinal cord white matter. Expression of viral antigens was followed by fibrinogen leakage from the blood vessels into brain parenchyma. This was shown by immunoperoxidase staining detecting fibrinogen extravascularly in central nervous system sections of infected mice. Simultaneously, expression of ICAM-1 (intercellular adhesion molecule 1) was induced on brain EC. SFV-A7 replicated in mouse brain microvascular EC in vitro and caused lysis of the cells. SFV-A7 did not induce ICAM-1 expression of mouse brain microvascular EC in vitro, while ICAM-1 was readily induced by gamma interferon and interleukin 1 beta. The observed increase of ICAM-1 expression on EC is immune mediated and not a direct effect of the virus infection. We conclude that SFV-A7 infection causes cerebral microvascular damage which contributes to the facilitation of experimental allergic encephalomyelitis in BALB/c mice.
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PMID:Semliki Forest virus infects mouse brain endothelial cells and causes blood-brain barrier damage. 791 58

Expression of adhesion molecules in immune-mediated diseases of the central nervous system was reviewed. In multiple sclerosis and experimental allergic encephalomyelitis (EAE), endothelial cells of active lesions increase expression of the adhesion molecules such as ICAM-1, VCAM-1 and inflammatory cells including memory T cells and macrophages express high levels of adhesion molecules such as LFA-1, VLA-4. Astrocytes also express CD44, ICAM-1, VCAM-1 and E-selectin in response to cytokine stimuli. In EAE, the majority of infiltrating cells are not MBP-specific memory T cells, thus it is speculated that the up-regulation of the adhesion molecules in the endothelial cells plays a decisive role in the development of immune-mediated diseases of the central nervous system. Therapeutic potency of clinical usage of anti-adhesion molecule antibodies has been explored.
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PMID:[Adhesion molecules and immune-mediated diseases of the central nervous system]. 799 76

The interaction between encephalitogenic lymphocytes and the cerebral microvascular lining is considered to be an important initial step in the recruitment of immune cells into the central nervous system (CNS) under pathological conditions such as multiple sclerosis (MS) and its investigative analog, experimental allergic encephalomyelitis (EAE). This study was conducted in order to examine whether differences in microvascular endothelial cell expression of several molecules involved in lymphovascular interactions correlate with the strain and organ-specific development of EAE. Cerebral and epididymal microvascular endothelial cells (EC) were isolated from SJL and B10.S mice, which, despite MHC-compatibility (H-2S), differ in their ability to develop EAE. The subcultured cells were then analyzed by flow cytometry for their ability to express class I MHC, class II MHC and ICAM-1 molecules in response to treatment with murine recombinant interferon-gamma (IFN-gamma). Over a range of doses and times, cerebral EC cultures derived from EAE-susceptible SJL mice expressed two-fold higher levels and higher cell surface densities of class II molecules than cerebral EC cultures derived from EAE-resistant B10.S mice, whereas class I and ICAM-1 molecules were comparably upregulated on both SJL and B10.S cerebral EC. In contrast, both SJL and B10.S epididymal EC cultures expressed lower but comparable levels of class II molecules in response to IFN-gamma. Class I and ICAM-1 molecules, however, were upregulated to at least the same degree as that observed on cerebral EC derived from both strains.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interferon-gamma-inducible endothelial cell class II major histocompatibility complex expression correlates with strain- and site-specific susceptibility to experimental allergic encephalomyelitis. 810 93

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