Biomedical subjects

P Vanguri

Publications and source records attributed to P Vanguri.

At least 19 recordsLinked to original sources

PubMed2005

Intracarotid transplantation of bone marrow stromal cells increases axon-myelin remodeling after stroke.

The present study investigates the induction of axon and myelin remodeling as a possible mechanism by which treatment of stroke with bone marrow stromal cells improves neurological functional recovery. Adult male Wistar rats were subjected to 2 h of middle cerebral artery occlusion, followed by an injection of 2 x 10(6) rat bone marrow stromal cells or phosphate-buffered saline into the internal carotid artery 24 h later. Animals were killed at 28 days after stroke. Functional tests, histo- and immunohistochemical staining were performed. Significant functional recovery was found after bone marrow stromal cell administration in all the three tests performed (modified neurological severity score, adhesive-removal and corner tests). Bone marrow stromal cell treatment markedly increased vessel sprouting, synaptophysin expression and NG2 positive cell numbers and density in the cortical peri-infarct area. In bone marrow stromal cell-treated rats, the number of Ki-67 positive proliferating cells and oligodendrocyte precursor cells in the corpus callosum increased significantly in concert with the enhancement of the areas of the corpus callosum in both hemispheres. These results suggest that bone marrow stromal cells facilitate axonal sprouting and remyelination in the cortical ischemic boundary zone and corpus callosum, which may underlie neurological functional improvement caused by bone marrow stromal cell treatment.

Animals↗

PubMed2002

Adult mesenchymal stem cells: potential for muscle and tendon regeneration and use in gene therapy.

The expansion potential and plasticity of stem cells, adult or embryonic, offer great promise for their use in medical therapies. Recent provocative data suggest that the differentiation potential of adult stem cells may extend to lineages beyond those usually associated with the germ layer of origin. In this review, we describe recent developments related to adult stem cell research and in particular, in the arena of mesenchymal stem cell (MSC) research. Research demonstrates that transduced MSCs injected into skeletal muscle can persist and express secreted gene products. The ability of the MSC to differentiate into cardiomyocytes has been reported and their ability to engraft and modify the pathology in infarcted animal models is of great interest. Research using MSCs in tendon repair provides information on the effects of physical forces on phenotype and gene expression. In turn, MSCs produce changes in their matrix environment in response to those biomechanical forces. Recent data support the potential of MSCs to repair tendon, ligament, meniscus and other connective tissues. Therapeutic applications of adult stem cells are approaching clinical use in several fields, furthering the possibility to regenerate damaged and diseased tissue.

Journal Article↗

PubMed2000

Human mesenchymal stem cells support megakaryocyte and pro-platelet formation from CD34(+) hematopoietic progenitor cells.

Megakaryocytopoiesis and thrombocytopoiesis result from the interactions between hematopoietic progenitor cells, humoral factors, and marrow stromal cells derived from mesenchymal stem cells (MSCs) or MSCs directly. MSCs are self-renewing marrow cells that provide progenitors for osteoblasts, adipocytes, chondrocytes, myocytes, and marrow stromal cells. MSCs are isolated from bone marrow aspirates and are expanded in adherent cell culture using an optimized media preparation. Culture-expanded human MSCs (hMSCs) express a variety of hematopoietic cytokines and growth factors and maintain long-term culture-initiating cells in long-term marrow culture with CD34(+) hematopoietic progenitor cells. Two lines of evidence suggest that hMSCs function in megakaryocyte development. First, hMSCs express messenger RNA for thrombopoietin, a primary regulator for megakaryocytopoiesis and thrombocytopoiesis. Second, adherent hMSC colonies in primary culture are often associated with hematopoietic cell clusters containing CD41(+) megakaryocytes. The physical association between hMSCs and megakaryocytes in marrow was confirmed by experiments in which hMSCs were copurified by immunoselection using an anti-CD41 antibody. To determine whether hMSCs can support megakaryocyte and platelet formation in vitro, we established a coculture system of hMSCs and CD34(+) cells in serum-free media without exogenous cytokines. These cocultures produced clusters of hematopoietic cells atop adherent MSCs. After 7 days, CD41(+) megakaryocyte clusters and pro-platelet networks were observed with pro-platelets increasing in the next 2 weeks. CD41(+) platelets were found in culture medium and expressed CD62P after thrombin treatment. These results suggest that MSCs residing within the megakaryocytic microenvironment in bone marrow provide key signals to stimulate megakaryocyte and platelet production from CD34(+) hematopoietic cells.

Antigens, CD↗

PubMed1998

IP-10 gene transcription by virus in astrocytes requires cooperation of ISRE with adjacent kappaB site but not IRF-1 or viral transcription.

Transcription of the IP-10 gene requires interferon (IFN)-stimulated response element (ISRE) and kappaB sites to be induced by lipopolysaccharide (LPS), IFN-gamma, virus, and poly(I:C). A requirement for Stat1 binding to ISRE for IFN-gamma and IFN regulatory factor-1 (IRF-1) binding to ISRE for LPS, poly(I:C), and virus has been reported. We investigated whether viral transcription is required for IP-10 induction and how ISRE interacts with IRF-1 and with two kappaB sites. IP-10 mRNA was induced by Newcastle disease virus and Sendai virus in rat astrocytes and the human astrocytoma U251 cell line. IP-10 was also induced by UV-irradiated virus, which is unable to carry out viral transcription. The minimal IP-10 virus response element (VRE) consists of an ISRE and adjacent kappaB site between -236 and -153, to which p50/p65 NF-kappaB proteins and IRF-like proteins bind. Virus induced NF-kappaB binding to an isolated kappaB sequence adjacent to ISRE. However, no protein binding to isolated ISRE was induced by virus. Virus also induced IP-10 in cells expressing a defective IRF-1 gene. Therefore, effective ISRE activity of IP-10 VRE may require an IRF-like protein binding, which is enhanced by an NF-kappaB heterodimer binding to an adjacent KB site. IRF-1 is not required for virus-induced IP-10 gene expression.

Animals↗

PubMed1997

Induction of IP-10 chemokine promoter by measles virus: comparison with interferon-gamma shows the use of the same response element but with differential DNA-protein binding profiles.

Measles virus (MV) and interferon (IFN)-gamma induced IP-10 chemokine mRNA in U373 glioblastoma cells. The minimal response element for both MV and IFN-gamma was localized between nucleotide -231 and -153 of muIP-10 promoter, which contains an IFN-stimulated response element (ISRE) and the distal NF-kappa Bd site. Mutation of individual elements showed that ISRE and NF-kappa Bd were required to function together. DNA-protein binding profiles with the minimal response element showed that IFN-gamma induced a complex consisting of STAT1 while MV induced a complex consisting of p50 and p65 in the absence of new protein synthesis. IFN-gamma and MV also induced IRF-1 DNA binding activity which persisted for longer time periods with IFN-gamma stimulation. Despite the functional requirement of both ISRE and NF-kappa Bd elements, different combinations of DNA binding factors are used in the induction of IP-10 by MV or IFN-gamma.

Base Sequence↗

PubMed1997

Ia expression and antigen presentation by glia: strain and cell type-specific differences among rat astrocytes and microglia.

Astrocytes from experimental allergic encephalomyelitis (EAE)-susceptible Lewis rats expressed higher levels of Interferon-gamma-inducible Ia than astrocytes from EAE-resistant Brown Norway (BN) rats, whereas BN microglia expressed higher Ia than Lewis at both mRNA and protein levels. Lewis astrocytes induced proliferation of MBP-specific T cells selected on Lewis background as efficiently as Lewis thymocytes, whereas BN astrocytes were much less efficient in stimulating T cells selected in the presence of BN thymocytes. Microglia, irrespective of strain, induced only weak proliferative responses of these T cells despite the high expression of Ia. Antigen-stimulated T cells underwent apoptosis in the presence of microglia but not astrocytes. Thus, astrocyte-mediated proliferation of MBP-specific T cells may contribute to the development of EAE, while microglia-induced T cell apoptosis may downregulate immunopathological processes in the brain.

Animals↗

PubMed1997

Dibutyryl cyclic AMP and inflammatory cytokines mediate C3 expression in Schwann cells.

Schwann cells (SchC), the myelinating glia of the peripheral nervous system, are immunocompetent cells and secrete a variety of immune and inflammatory mediators. In this report, we show that rat SchC in vitro express both C3 mRNA and protein in response to dibutyryl cyclic AMP (dbcAMP) and the cytokines IFN-gamma, TNF-alpha, and IL-1beta. SchC in culture constitutively expressed low levels of C3 which were significantly upregulated upon stimulation with 1mM dbcAMP by 24 hours, and persisted up to 120 hours. This response was minimally enhanced by costimulation with 100 U/ml IFN-gamma, whereas costimulation with 100 U/ml IFN-gamma together with 150-450 ng/ml TNF-alpha induced a greatly increased C3 response. TNF-alpha alone did not induce C3 expression in SchC. Cycloheximide inhibited this dbcAMP-dependent delayed C3 production, thus implying an intermediary signal in the induction pathway requiring protein synthesis. Treatment with 0.1-10 ng/ml IL-1beta for 0-72 hours induced C3 mRNA and protein in a dose-dependent manner. C3 mRNA was detectable at 1 hour and mRNA and protein peaked by 6-12 hours on stimulation with 10 ng/ml IL-1beta, or at 48 hours with 1.0 ng/ml IL-1beta. Furthermore, IL-1beta mRNA was detected at 6 hours in dbcAMP-treated SchC, preceding the dbcAMP-induced C3 expression by 18 hours. Induction of C3 mRNA and protein by dbcAMP at 24 hours was inhibited >85% by a neutralizing anti-IL-1beta antibody and 76% with an IL-1 receptor antagonist. This suggests that dbcAMP-induced synthesis of IL-1beta mediates the C3 production by SchC in an autocrine/paracrine fashion by binding to a functional IL-1 receptor expressed on the surface of SchC. Endoneurial IL-1 and C3 production by SchC may therefore contribute to the inflammatory events associated with peripheral nerve demyelination.

Animals↗

PubMed1996

Interferon-inducible protein-10 identified as a mediator of tumor necrosis in vivo.

Human Burkitt lymphoma cell lines give rise to progressively growing subcutaneous tumors in athymic mice. These tumors are induced to regress by inoculation of Epstein-Barr virus-immortalized normal human lymphocytes. In the present study, analysis of profiles of murine cytokine/chemokine gene expression in Burkitt tumor tissues excised from the nude mice showed that expression of the murine alpha-chemokine interferon-inducible protein-10 (IP-10) was higher in the regressing than in the progressive Burkitt tumors. We tested the effects of IP-10 on Burkitt tumor growth in nude mice. Inoculation of established Burkitt tumors either with crude preparations of murine IP-10 or with purified human IP-10 caused visible tumor necrosis in a proportion of the animals, although no complete tumor regressions were observed. Constitutive expression of murine IP-10 in Burkitt cells reduced their ability to grow as subcutaneous tumors, and caused visible tumor necrosis in a proportion of the animals. Histologically, IP-10-treated and IP-10-expressing Burkitt tumors had widespread evidence of tumor tissue necrosis and of capillary damage, including intimal thickening and vascular thrombosis. Thus, IP-10 is an antitumor agent that promotes damage in established tumor vasculature and causes tissue necrosis in human Burkitt lymphomas established subcutaneously in athymic mice.

Animals↗

PubMed1996

Role of muIP-10 in interferon-gamma induction of Ia in rat astrocytes.

Interferon-gamma, (IFNgamma) is a potent inducer of class II MHC (Ia) in rat astrocytes and microglia which are immunocompetent cells of the central nervous system (CNS). muIP-10, a member of the alpha-chemokine family, is also induced by IFNgamma in these cells. The induction of muIP-10 mRNA occurred in an immediate early manner, while Ia mRNA-induction was delayed and required new protein synthesis. We studied the possible role of muIP-10 in IFNgamma-mediated induction of Ia in astrocytes. Antibodies to muIP-10 protein significantly inhibited the expression of surface Ia molecules by astrocytes. Incubation of astrocytes with antisense-oligonucleotides against muIP-10 mRNA also reduced the number of Ia positive cells inducible by IFNgamma. Neither the number of IFNgamma-inducible class I MHC positive cells nor the number of class I molecules expressed per cell were affected by antisense-oligonucleotides against muIP-10, indicating the specificity of the oligonucleotide and the selective requirement of muIP-10 for Ia induction by IFNgamma. Transient transfection of astrocytes with plasmids expressing muIP-10 in the antisense orientation also reduced the number of Ia positive astrocytes. These studies suggest a role for muIP-10 protein as an autocrine factor that enhances the expression of IFNgamma-inducible Ia on astrocytes. This could create focal areas rich in Ia expressing cells which could more efficiently present antigens to T cells, leading to immune-mediated inflammation such as in multiple sclerosis.

Animals↗

PubMed1996

Chronic intrathecal infusion of phosphorothioate or phosphodiester antisense oligonucleotides against cytokine responsive gene-2/IP-10 in experimental allergic encephalomyelitis of lewis rat.

The role of CRG-2 protein (murine IP-10) in experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis, was tested by blocking crg-2 mRNA synthesis using chronic infusion of antisense oligonucleotides into lumbar subarachnoid space by osmotic minipumps. After injection with myelin basic protein, rats developed hind limb paralysis and their spinal cords showed crg-2 mRNA expression and the presence of inflammation. When antisense phosphorothioate oligonucleotides to crg-2 (AS-PScrg2) or nonspecific oligonucleotides (AS-PSscram) were infused at rates from 0.18 to 5.4 nmol/hr, they caused hind limb paralysis that was clinically different from EAE and tissue necrosis of the spinal cord. Natural phosphodiester (AS-PO) oligonucleotides that were infused at rates from 1.8 to 5.4 nmol/hr had no toxic effects. AS-POcrg2 reduced the initial appearance of crg-2 mRNA and this may be responsible for the significant reduction in the EAE scores at the height of clinical disease. The antisense treatment did not alter inflammation of the spinal cord. While AS-PS oligonucleotides were unsuitable for intrathecal administration, AS-POcrg2 were not toxic and reduced paralysis due to EAE.

Animals↗

PubMed1995

Human Mig chemokine: biochemical and functional characterization.

Mig is a chemokine of the CXC subfamily that was discovered by differential screening of a cDNA library prepared from lymphokine-activated macrophages. The mig gene is inducible in macrophages and in other cells in response to interferon (IFN)-gamma. We have transfected Chinese hamster ovary (CHO) cells with cDNA encoding human Mig and we have derived CHO cell lines from which we have purified recombinant human Mig (rHuMig). rHuMig induced the transient elevation of [Ca2+]i in human tumor-infiltrating T lymphocytes (TIL) and in cultured, activated human peripheral blood-derived lymphocytes. No responses were seen in human neutrophils, monocytes, or Epstein-Barr virus-transformed B lymphoblastoid cell lines. rHuMig was chemotactic for TIL by a modified Boyden chamber assay but rHuMig was not chemotactic for neutrophils or monocytes. The CHO cell lines, IFN-gamma-treated human peripheral-blood monocytes, and IFN-gamma-treated cells of the human monocytic cell line THP-1 all secreted multiple and identical HuMig species as revealed by SDS-PAGE. Using the CHO-derived rHuMig, we have shown that the species' heterogeneity is due to proteolytic cleavage at basic carboxy-terminal residues, and that the proteolysis occurs before and not after rHuMig secretion by the CHO cells. The major species of secreted rHuMig ranged from 78 to 103 amino acids in length, the latter corresponding to the full-length secreted protein predicted from the HuMig cDNA. Carboxy-terminal-truncated forms of rHuMig were of lower specific activity compared to full-length rHuMig in the calcium flux assay, and the truncated species did not block the activity of the full-length species. It is likely that HuMig plays a role in T cell trafficking and perhaps in other aspects of the physiology of activated T cells.

Amino Acid Sequence↗

PubMed1995

Regulatory mechanisms of MuRantes and CRG-2 chemokine gene induction in central nervous system glial cells by virus.

In this report we characterize the induction mechanisms of two chemokine genes, MuRantes and crg-2, the murine homologs of human RANTES and IP-10, respectively, in primary rat astrocytes and microglia by the neurotropic paramyxovirus, Newcastle Disease Virus (NDV). The time course for NDV induction of both MuRantes and crg-2 genes in astrocytes and microglia was similar, with peak mRNA expression at 10-12 h. Unlike crg-2, MuRantes mRNA was not induced by IFN-gamma. MuRantes and crg-2 are transcriptionally induced by noninfectious, UV-irradiated NDV in astrocytes and microglia, unlike TNFalpha gene transcription, which is induced only by live NDV. These data indicate that signals generated through virus-receptor interaction on the target cell surface suffice to initiate MuRantes and crg-2 gene transcription in the absence of viral replication. In astrocytes, MuRantes mRNA accumulation in response to NDV was completely blocked by tyrosine kinase inhibitors, and partially by PKC and PKA inhibitors, whereas crg-2 mRNA accumulation was significantly inhibited by PKC inhibitors, but minimally or not affected by inhibitors of tyrosine kinase or PKA activity. These kinase inhibitors also affected MuRantes and crg-2 gene transcription in similar patterns to those observed for mRNA levels, but did not reduce the mRNA stability. Therefore, the signals required for mRNA accumulation appear to operate at the level of transcription. Efficient transcription of MuRantes and crg-2 genes may require different sets of transcriptional proteins and enhancers that are regulated by different signaling pathways activated by NDV.

Amino Acid Sequence↗

PubMed1995

Interferon-gamma-inducible genes in primary glial cells of the central nervous system: comparisons of astrocytes with microglia and Lewis with brown Norway rats.

We compared the expression of various interferon-gamma (IFN-gamma)-inducible mRNAs in primary rat astrocytes and microglia. Of 11 different mRNAs inducible by IFN-gamma in a macrophage cell line, RAW 264.7, only eight were induced in both types of glia, which included mRNAs encoding the transcriptional factors, IRF-1, LRF-1 and ZIF-268; members of the chemokine family, crg-2/IP-10 and MIG; beta 2-microglobulin and metallothionein-II. The patterns of induction of the mRNAs were more similar between astrocytes and microglia than with RAW 264.7 cells. Comparison of astrocytes from Lewis and Brown Norway rats showed no major differences in the levels of the crg mRNAs or in the amount of Crg-2 protein induced by IFN-gamma.

Activating Transcription Factor 3↗

PubMed1994

IFN and virus-inducible expression of an immediate early gene, crg-2/IP-10, and a delayed gene, I-A alpha in astrocytes and microglia.

IFN-gamma is a potent macrophage activator and induces a number of early and delayed genes. crg-2, the presumed murine homologue of human IP-10, belongs to a family of proinflammatory chemokines and is induced as an immediate early gene in response to IFN-gamma in macrophages. In contrast, class II MHC or Ia genes which are essential for Ag presentation are induced as a delayed response to IFN-gamma. We studied the expression of crg-2 and compared it with Ia in astrocytes and microglia of the central nervous system since, like macrophages, these cells can also produce a number of cytokines, express Ia molecules, and present Ag. We showed that crg-2 mRNA was induced in astrocytes and microglia by IFN-gamma as well as a paramyxovirus, Newcastle disease virus (NDV). Crg-2 protein was detected in the cytoplasm and in the supernatants of IFN-gamma-treated astrocytes and microglia. IFN-gamma and NDV or UV irradiated-NDV (UV-NDV) also induced Ia mRNA in these cells. The kinetics of expression of crg-2 and Ia mRNA were compared in the same systems. While crg-2 mRNA appeared within 2 h and reached a maximum in 6 to 8 h, Ia mRNA was not detected before 8 h. Cycloheximide superinduced crg-2 mRNA induced by IFN-gamma or UV-NDV but it abolished Ia mRNA induction by the same stimuli. The induction of crg-2 in astrocytes and microglia likely contributes to the development of immune-mediated inflammation in response to viruses or in autoimmune diseases of the central nervous system.

Animals↗

PubMed1993

Hydrolysis of myelin basic protein in myelin membranes by granzymes of large granular lymphocytes.

Immune-mediated demyelination initially manifests as a separation of myelin lamellae followed by loss of myelin proteins and eventual loss of myelin membranes. Myelin basic protein, one of the major structural proteins of myelin, is highly vulnerable to various proteases derived from diverse cell types. Killer lymphocytes such as CTL, in addition to other immune effectors, have been implicated in inflammatory demyelination. In addition to a pore forming peptide, the granules of CTL and large granular lymphocytes (LGL) contain a number of serine esterases collectively called as granzymes. We studied the effect of these granule enzymes on myelin and found that LGL granule-extracts (LGL-g) hydrolyzed MBP in myelin membranes. LGL-g also cleaved purified MBP at neutral pH in a Ca2+ independent manner and this hydrolysis was inhibited by serine esterase inhibitors. In addition, absorption of LGL-g with antigranzyme A significantly reduced MBP hydrolysis. These findings implicated the granzymes in LGL-g, especially granzyme A, as the agent causing MBP degradation. Inasmuch as activation of CTL in the vicinity of myelinated axons can lead to granule exocytosis, hydrolysis of MBP by granzymes may be a significant event in myelin destruction.

Cell Membrane↗

PubMed1992

Glutamate differentially inhibits the expression of class II MHC antigens on astrocytes and microglia.

MHC molecules are required for Ag recognition by T cells. Inasmuch as cells in the central nervous system do not express MHC constitutively, appearance of MHC, in inflammatory and degenerative diseases of the brain, may indicate local Ag presentation and subsequent immune response. Although both astrocytes and microglia are capable of class II MHC expression in vitro, in vivo studies failed to show the presence of significant amounts of class II on astrocytes compared to microglia. Our study is designed to clarify possible regulatory mechanisms that can explain the differences in inducibility of class II MHC between astrocytes and microglia in vivo. Using dissociated rat brain cell cultures, we have found that glutamate, an excitatory neurotransmitter, exerted a profound inhibitory effect on IFN-gamma-induced expression of class II on astrocytes, but not on microglia. Both glutamate and norepinephrine, a neurotransmitter previously reported to down-regulate class II on astrocytes, inhibited the induction of class II on astrocytes by eliminating accumulation of class II MHC mRNA. The kinetics of class II mRNA induction by IFN-gamma in the presence of glutamate suggested that glutamate may act as a transcriptional inhibitor. It is likely that class II induction on astrocytes in vivo may be selectively down-regulated by neurotransmitters such as glutamate and norepinephrine.

Animals↗

PubMed1990

Identification of CRG-2. An interferon-inducible mRNA predicted to encode a murine monokine.

In order to identify novel proteins produced by activated macrophages, a cDNA library was made from cultures of the mouse macrophage-like cell line RAW 264.7 that had been treated with conditioned medium from mitogen-stimulated spleen cells, and the library was screened by differential plaque hybridization. A cDNA clone was isolated that detected a 1.4-kilobase mRNA that accumulated dramatically in response to the spleen cell conditioned medium. The 1.4-kilobase mRNA encodes a predicted protein of 98 amino acids, designated CRG-2, molecular weight (Mr) 10,781, with a 21-residue signal peptide. The amino acid sequence indicates that CRG-2 is a member of the platelet factor 4 family (PF4) of cytokines. The CRG-2 mRNA was induced by alpha-, beta-, and gamma-interferons (IFNs) and by lipopolysaccharide. In response to IFN-gamma, the CRG-2 mRNA level reached a peak between 3 and 6 h. The accumulation of CRG-2 mRNA was not blocked by cycloheximide. Among the known members of the PF4 family, CRG-2 is most closely related to the interferon-inducible human protein IP-10. The 5'-flanking region of the crg-2 gene was isolated, and comparisons between crg-2 and IP-10 genes, mRNAs, and proteins reveal conserved features of possible functional importance. CRG-2 may play a role in host defense, particularly in the response to viral infection.

Amino Acid Sequence↗

PubMed1988

Hydrolysis of myelin basic protein in human myelin by terminal complement complexes.

The participation of terminal complement complexes (TCC) in demyelination has been shown in rodent cerebellar cultures. Since TCC modulates activities of various membrane-associated enzymes and increases the level of cellular Ca2+ we investigated whether TCC could activate Ca2+-dependent neutral proteases in myelin that would lead to hydrolysis of myelin basic protein (BP). Addition of antibody and C7-deficient serum plus C7 to sealed myelin vesicles of two to six bilayers caused significant BP hydrolysis compared to the hydrolysis caused by antibody and C7-deficient serum. Significant hydrolysis occurred at the stage of C5b6,7 assembly, which increased in magnitude at the C5b6-8 stage. C5b6-9 formation did not enhance the effect of C5b6-8. BP hydrolysis by C5b6,7 did not require Ca2+ whereas the effect of C5b6-8/C5b6-9 was, in part, Ca2+-dependent. We postulated that TCC formation in myelin membranes causes activation of myelin-associated neutral proteases with subsequent hydrolysis of BP as a consequence of complement peptide insertion and channel formation. Such processes may alter the structure of myelin and augment the action of other inflammatory cells and their products in demyelinating diseases that could ultimately lead to the loss of myelin.

Complement Membrane Attack Complex↗