Biomedical subjects

S Jander

Publications and source records attributed to S Jander.

45 records · Page 3Linked to original sources

PubMed1996

Downregulation of microglial keratan sulfate proteoglycans coincident with lymphomonocytic infiltration of the rat central nervous system.

The monoclonal antibody (MAb) 5D4 against a keratan sulfate (KS) epitope of bovine cartilage proteoglycan stains ramified microglia in the rat brain. In this study we show that 5D4-positive microglia is abundant in the normal rat spinal cord and nearly absent during both the active and recovery phase of experimental autoimmune encephalomyelitis (EAE) in myelin-immunized Lewis rats. In contrast, during Wallerian degeneration of the optic nerve the density of KS-immunoreactive microglia remains constant. KS immunoreactivity is absent from both normal and transected sciatic nerves, and spinal nerve roots. On immunoblots of spinal cord extracts MAb 5D4 stains a novel type of KS proteoglycans (KSPGs) with an apparent molecular weight mainly between 140 and 200 kd, which significantly decrease in acute EAE. Our data suggest that high levels of KSPG expression correlate to a downregulated immunophenotype of resident macrophages in the nervous system. The lack of detectable KS in peripheral nerve points to a divergent differentiation of bone marrow-derived resident macrophages in the peripheral and central nervous systems and may partially account for the rapid macrophage response to axonal injury in the peripheral nervous system. Downregulation of microglial KSPG could be a prerequisite for a rapid inflammatory response in the central nervous system.

Animals↗

PubMed1995

Lymphocytic infiltration and expression of intercellular adhesion molecule-1 in photochemically induced ischemia of the rat cortex.

The contribution of the immune system to the pathogenesis of ischemic lesions is still uncertain. We have analyzed leukocyte infiltration in photochemically induced focal ischemia of the rat parietal cortex by immunocytochemistry. Between 1 and 2 days after photothrombosis, CD5+ T cells adhered to subpial and cortical vessels and infiltrated the ischemic lesion prior to macrophages. By day 3 numerous T cells and some macrophages, whose number increased further between day 3 and day 7, had infiltrated the border zone around the lesion sparing the center. In addition, CD5-/CD8+ lymphocytes that probably represent natural killer cells were found. Intercellular adhesion molecule-1 (ICAM-1) was expressed on endothelial cells on days 1 and 2 and in the border zone on infiltrating leukocytes from day 3 to day 7. Starting on day 7, macrophages infiltrated the core of the lesion to remove debris. When the entire lesion was covered by macrophages at day 14, the number of T cells had decreased and ICAM-1 immunoreactivity was no longer found in or around the infarct. In conclusion, our study shows that ischemic lesions can lead to a local immune reaction in the CNS. Thus, blocking of lymphocyte-derived cytokines or cell adhesion molecules may provide a new approach to confining the sequelae of stroke.

Animals↗

PubMed1994

Local immune responses in the rat cerebral cortex after middle cerebral artery occlusion.

This study describes local immune responses in cerebral ischemia induced by permanent occlusion of the middle cerebral artery (MCAO) in the rat. The temporal and spatial pattern of leukocyte infiltration was characterized immunocytochemically using monoclonal antibodies against CD5, a pan T cell marker, against CD4 and CD8 for subtyping of T lymphocytes, and ED1, a marker for macrophages. CD5+ T cells were present in some animals on the pial surface at day 1 and with increasing numbers mainly at the edges of the infarcts at days 3 and 7. By day 14 their number had significantly decreased. Subtyping of T lymphocytes revealed that CD4+ helper/inducer T cells were rare, while CD8+ lymphocytes were abundant. Moreover, CD8+ lymphocytes outnumbered CD5+ T cells indicating the presence of CD5-/CD8+ natural killer (NK) cells. ED1+ macrophages primarily infiltrated the core of the infarct starting on day 1. Infiltrating leukocytes expressed leukocyte function associated antigen-1 and MHC class I and II antigens. Early after infarction, increased expression of the intercellular adhesion molecule-1 was found on vessels and leukocytes. In conclusion, this study shows that lymphocytes enter the nervous system not only in autoimmune diseases, but also in response to primarily 'non-immune' neuronal damage such as stroke.

Animals↗

PubMed1994

Serum and cerebrospinal fluid levels of soluble intercellular adhesion molecule 1 (sICAM-1) in patients with HIV-1 associated neurological diseases.

We measured levels of soluble intercellular adhesion molecule 1 (sICAM-1) in paired serum and CSF samples of 110 HIV-1-positive patients with and without neurological symptoms and 40 HIV-negative non-immune neurological controls, and in sera of 26 asymptomatic HIV-1-positive patients. Serum sICAM-1 levels in asymptomatic HIV-1-positive patients were significantly increased in comparison to HIV-negative controls. Moreover, they were significantly higher in HIV-1-positive patients with AIDS-defining diseases than in the asymptomatic HIV-1-positive group. In subgroups of patients with neurological disease, the highest serum values were found in HIV encephalopathy. CSF levels of sICAM-1 were elevated only in HIV-1-positive patients with neurological disease mainly due to passive diffusion through a defective blood-brain barrier. An sICAM-1 index was calculated as a measure for intrathecal production of sICAM-1 but showed no significant differences between patients with and without neurological involvement. However, increased levels of the sICAM-1 index were found in some patients with opportunistic CNS infection of bacterial or fungal origin. Serum and CSF levels of sICAM-1 correlated with neopterin levels, a marker of interferon-gamma-mediated macrophage activation and CSF sICAM-1 levels were inversely correlated to numbers of CD4+ T cells. Elevated serum sICAM-1 levels already in asymptomatic HIV-1-positive individuals add to the evidence for an early immune activation in HIV infection. With the further increase of serum and CSF s-ICAM-1 in patients with AIDS-defining diseases sICAM-1 could serve as a new surrogate marker similar to neopterin.

AIDS Dementia Complex↗

PubMed1993

Tumor necrosis factor-alpha in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous system.

This study reports on the immunocytochemical localization of tumor necrosis factor-alpha (TNF alpha) in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous system (PNS) using teased nerve fiber preparations. In experimental autoimmune neuritis induced by active immunization (EAN) or by adoptive transfer of autoreactive T cells (AT-EAN), macrophages passing blood vessels as well as macrophages adherent to nerve fibers were TNF alpha-positive. Large post-phagocytic macrophages at later stages of demyelination were TNF alpha-negative. Intraperitoneal application of an anti-TNF alpha antibody to EAN rats significantly reduced the degree of inflammatory demyelination, suggesting a pathogenic role for TNF alpha. After nerve transection only macrophages located within degenerating nerve fibers were TNF alpha-positive, while those entering and leaving nerves were negative. TNF alpha produced by macrophages seems to be involved in immune-mediated demyelination and non-immune myelin degradation after axotomy. While interferon-gamma (IFN gamma) is present in EAN nerves and may act as a local stimulus for TNF expression, the nature of this signal in Wallerian degeneration in the absence of IFN gamma is unknown.

Animals↗

PubMed1993

Serum and CSF levels of soluble intercellular adhesion molecule-1 (ICAM-1) in inflammatory neurologic diseases.

Intercellular adhesion molecule-1 (ICAM-1), a cell surface receptor important for cellular interactions in immune responses, especially leukocyte trafficking into inflamed tissue, is released in a soluble form (sICAM-1) into the extracellular space. In this study, we measured sICAM-1 in paired serum and CSF samples from patients with inflammatory diseases of the nervous system (IND) and calculated a sICAM-1 index as a measure of the intrathecal release of ICAM-1. In comparison with noninflammatory neurologic disease (NIND) controls, we found increased sICAM-1 index levels in viral meningoencephalitis, bacterial meningitis and, to a lesser degree, multiple sclerosis but not in Guillain-Barré syndrome. Serial examination of viral meningoencephalitis patients in most cases showed a decrease of sICAM-1 index in parallel with falling cell counts and clinical improvement. Except for those in bacterial meningitis, sICAM-1 serum levels of IND patients were not significantly different from those of NIND controls. The increased intrathecal release of sICAM-1 in viral meningoencephalitis and bacterial meningitis most likely reflects activation of macrophages and lymphocytes and provides evidence for a strong local immune response that itself, in addition to the infectious agent, may damage nervous tissue.

Cell Adhesion Molecules↗

PubMed1993

Macrophages and endothelial cells express intercellular adhesion molecule-1 in immune-mediated demyelination but not in Wallerian degeneration of the rat peripheral nervous system.

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) plays an important role in immune responses, especially in T cell/endothelial cell and T cell/macrophage interactions. This study reports the cellular localization of ICAM-1 during immune-mediated demyelination of the peripheral nervous system induced by adoptive transfer of P2 specific T cells. EXPERIMENTAL DESIGN: Cryosections 1 micron thick of ventral roots of rats with experimental autoimmune neuritis were labeled with a monoclonal antibody against rat ICAM-1. RESULTS: Numerous ICAM-1 positive cells were present before and shortly after the onset of clinical disease from days 4 to 6 after cell transfer. By day 8, their number had greatly decreased. ICAM-1 positive infiltrating cells could be identified as ED1 positive macrophages. Moreover, endothelial cells expressed ICAM-1. Schwann cells and T cells were ICAM-1 negative. While at early stages of experimental autoimmune neuritis, ICAM-1 and Ia colocalized on macrophages but not endothelial cells, Ia persisted for a longer period in nerve roots than ICAM-1. After nerve transection, macrophages entering the distal stump and endothelial cells did not express ICAM-1. CONCLUSIONS: The presence of ICAM-1 immunoreactivity in peripheral nerve indicates an underlying immune-mediated process. Among other cytokines interferon-gamma, which is transiently expressed in nerves during immune-mediated demyelination but not after nerve transection, could be one mediator that induces ICAM-1 in immune-mediated demyelination of the peripheral nervous system.

Animals↗

PubMed1991

Presence of the terminal complement complex (C5b-9) precedes myelin degradation in immune-mediated demyelination of the rat peripheral nervous system.

In this study, the terminal complement complex C5b-9 (TCC) was localized by immunocytochemistry at different clinical stages of experimental autoimmune neuritis. Deposits of TCC were found on the surface of Schwann cells and their myelin sheaths, and to some extent in the extracellular space at predilective sites of impending demyelination before onset of clinical signs and for a short period thereafter. Additionally, TCC was deposited on the surface of W3/13 positive leukocytes. No TCC immunoreactivity was seen in the distal stump of transected sciatic nerves 1 to 15 days after axotomy. The early and transient deposition of TCC on Schwann cells and myelin sheaths in experimental autoimmune neuritis before overt demyelination suggests that complement activation plays a pathogenic role in the initiation of immune-mediated myelin damage. The lack of TCC immunoreactivity after nerve transection excludes a nonspecific activation process. The signals involved in local TCC formation in demyelinating peripheral nervous system disorders have yet to be explored.

Animals↗

PubMed1989

Topology of proteolipid protein in the myelin membrane of central nervous system. A study using antipeptide antibodies.

Peptides according to amino-acid sequences of the N- and C-terminus of lipophilin (proteolipid protein, PLP) (Gly1-Phe15 = 1; Thr261-Phe276 = 6) and of the other four hydrophilic domains (Glu37-Leu60 = 2; Arg97-Leu112 = 3; Gly119-Gly127 = 3A; Trp144-Tyr156 = 3B; Lys191-Ala203 = 4; Asn222-Phe232 = 5) have been synthesized by the solid-phase Fmoc method, linked covalently to keyhole limpet hemocyanin (KLH) and used as antigens. Monospecific antibodies against these antigens were isolated by affinity chromatography. Each antibody recognized its epitope in isolated partially delipidated PLP with the ELISA technique, western blot, thin sections of paraffin embedded rat brains and in the plasma membrane of appropriately fixed/permeabilized rat oligodendrocytes in culture. After fixation with formaldehyde antipeptide 3A antibody stained intact non-permeabilized cells. Therefore the epitope 3A must be located on the extracellular surface of the membrane. This is in full support of our previous biochemical results on the orientation of lipophilin in the myelin membrane.

Amino Acid Sequence↗