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PubMed1998

Soluble complement receptor type I limits damage during revascularization of ischemic myocardium.

BACKGROUND: This study was undertaken to determine whether suppression of complement activation with soluble human complement receptor type I reduces myocardial damage during the revascularization of ischemic myocardium. METHODS: In 20 pigs, the second and third diagonal coronary arteries were occluded for 90 minutes, followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. In 10 pigs, soluble human complement receptor type I (10 mg/kg) was infused over 30 minutes before the period of coronary occlusion; 10 other pigs received no soluble human complement receptor type I. Complement activation was measured by total hemolytic complement activity (expressed as a percentage of preischemic values). Ischemic damage was assessed by changes in myocardial tissue pH, wall motion scores (range, 4=normal to -1=dyskinesia), and infarct size (area of necrosis versus area at risk). RESULTS: After 180 minutes of reperfusion, hearts treated with soluble human complement receptor type I had significantly less complement activation than nontreated hearts (1.1%+/-0.09% versus 7.8%+/-0.04%, respectively; p < 0.002), less myocardial acidosis (-0.41+/-0.03 versus -0.72+/-0.03, respectively; p < 0.0001), higher wall motion scores (3.1+/-0.09 versus 1.67+/-0.16, respectively; p < 0.0001), and smaller infarct size (24.6%+/-2.0% versus 41%+/-1.3%, respectively; p < 0.0001). CONCLUSIONS: Complement inhibition with soluble human complement receptor type I significantly limits ischemic damage during the revascularization of acutely ischemic myocardium.

Acidosis↗
PubMed1997

Effect of whole and fractionated intravenous immunoglobulin on complement in vitro.

Intravenous immunoglobulins (IVIG) are increasingly used for treatment of inflammatory diseases, and the modulation of complement may contribute to some of its beneficial effects. IVIG may bind C1q and activated C3 and C4, and enhance inactivation of C3b. We have previously shown that IVIG inhibited complement-mediated lysis solely via its Fc part through interaction with the classical pathway. In the present study we have investigated whole IVIG (Octagam, and Sandoglobulin) and the monomer, dimer and multimer fractions of Octagam with respect to complement activation in serum and inhibition of complement lysis of red cells. The isolated fractions were found to be stable, homogeneous (monomer, dimer or multimer) and pure (virtually only IgG). Both whole IVIG and its fractions significantly activated complement in serum and inhibited hemolysis compared with human albumin. These effects were most pronounced in the monomer, less in the multimer and least in the dimer fraction. The complement activation was shown to be mediated through the classical pathway since formation of C1rs-C1inh complexes and C4bc were increased, in contrast to Bb. Surprisingly, heat aggregation of Octagam was not followed by a corresponding increase in complement activation, as would be expected, unless it was dialysed before heating, suggesting that it is stabilized to avoid excess activation. In conclusion, the results support the hypothesis that IVIG causes a mild activation of complement in vitro. We suggest that this effect may contribute to the complement inhibitory properties of IVIG by diverting complement deposition from the target to the fluid phase.

Animals↗
PubMed1997

Characterization of neuronal cell death induced by complement activation.

The complement system plays an important role in human immune defense mechanism. Its activation via either the classical or the alternative pathway can lead to the formation of membrane attack complex (MAC) and subsequently kills target cells. Activation of the classical pathway can be initiated with binding of C1q which is first factor of complement cascade to the Fc (fragment crystalline) region of immunoglobulin. This triggers a cascade of proteolytic events resulting in the activation of C5 convertase which cleaves C5 into C5b and C5a. The C5b then binds C6, C7, C8 to form a C5b-8 complex. Binding of C9 molecules to C5b-8 forms C5b-9, the MAC, which pore size increases as the number of C9 in the complex increases. If this membrane lesion persists and results in uncontrolled ion fluxes, the cells swell and eventually lyse. To restrict the activity of the complement system, endogenous complement inhibitors are available to regulate complement-mediated cytolysis. This enables the complement system to distinguish "self" from "foreign" and protect the host from inadvertent complement attack. Activation of the classical complement cascade has been reported in Alzheimer's disease and other neurodegenerative disorders. Recently, we demonstrated that complement activation causes neuronal cell death in vitro, and this neurodegenerative process is regulated by homologous restriction. In this article, we describe the use of two cell lines as in vitro models to evaluate cell injury/cell death induced by complement activation.

Animals↗
PubMed2000

Impaired human ovarian follicular fluid complement function in hereditary angioedema.

We sought and detected functionally active complement in human ovarian follicular fluid obtained during the peri-ovulatory period. All the functional complement activities tested, including total haemolytic complement, classical pathway activity, alternative pathway activity and C1 inhibitor function were present with values within the normal serum range. Active complement in follicular fluid is relevant for the function of the enzymatic multifactorial mechanism of ovulation. The presence in hereditary angioedema patients of both complement (C1 inhibitor deficiency and chronically consumed complement) and ovarian abnormalities (cystic ovaries), led us to study complement function in the follicular fluid of women of reproductive age affected with hereditary angioedema. In contrast to healthy women, hereditary angioedema patients showed dramatically reduced classical pathway activity and undetectable functional and antigenic C1 inhibitor. C4 was very low, while C3 and B were slightly reduced or within the normal serum range. This complement profile was also detected in patients' sera. Since hereditary angioedema patients often show cystic ovaries (polycystic or multifollicular), the presence of multifollicular ovaries in the two patients studied, along with complement dysfunction, may be relevant. These findings, as well as the normalisation of the ovaries found by us in hereditary angioedema patients and in the patients reported here who were undergoing danazol treatment, and the increase in C1 inhibitor and the improvement of clinical symptoms, suggest a further link between complement and ovarian function.

Adult↗
PubMed2006

Functional characterization of the complement control protein homolog of herpesvirus saimiri: ARG-118 is critical for factor I cofactor activities.

Herpesvirus saimiri (HVS) is a lymphotropic virus that causes T-cell lymphomas in New World primates. It encodes a structural homolog of complement control proteins named complement control protein homolog (CCPH). Previously, CCPH has been shown to inhibit C3d deposition on target cells exposed to complement. Here we have studied the mechanism by which it inactivates complement. We have expressed the soluble form of CCPH in Escherichia coli, purified to homogeneity and compared its activity to vaccinia virus complement control protein (VCP) and human complement regulators factor H and soluble complement receptor 1. The expressed soluble form of CCPH bound to C3b (KD = 19.2 microm) as well as to C4b (KD = 0.8 microm) and accelerated the decay of the classical/lectin as well as alternative pathway C3-convertases. In addition, it also served as factor I cofactor and supported factor I-mediated inactivation of both C3b and C4b. Time course analysis indicated that although its rate of inactivation of C4b is comparable with VCP, it is 14-fold more potent than VCP in inactivating C3b. Site-directed mutagenesis revealed that Arg-118, which corresponds to Lys-120 of variola virus complement regulator SPICE (a residue critical for its enhanced C3b cofactor activity), contributes significantly in enhancing this activity. Thus, our data indicate that HVS encodes a potent complement inhibitor that allows HVS to evade the host complement attack.

Arginine↗
PubMed1979

Complement-enhanced immunity to infection with Neisseria gonorrhoeae in mice.

Subcutaneous chambers were implanted in mice, injected with Neisseria gonorrhoeae, and supplemented with complement as a model for studying the immunogenicity and strain diversity of N. gonorrhoeae. Immunotypic resistance to N. gonorrhoeae in immunized mice was significantly (P less than 0.01) increased by injection of exogenous guinea pig complement into the host before challenge with gonococci. By using this model to test gonococcal isolates from various geographical areas, two highly immunogenic but immunotypically different gonococcal strains were identified. The piliated cells of these strains induced both complement-enhanced immunity and a degree of exogenous complement-independent immunity. The immunity in mice not treated with complement developed more slowly, was less effective, and waned earlier than that which was complement-dependent. Pretreatment with complement, although highly effective in preventing infection in immunized mice, was much less beneficial in terminating already established infections, even though bactericidal antibodies were present at the time of complement treatment. The mouse chamber model in which both complement-mediated and complement-independent mechanisms of protection can be evaluated may provide an additional tool for elucidating the immunology of gonococcal or other microbial infections.

Animals↗
PubMed2003

Inhibition of complement factor C5 protects against renal ischemia-reperfusion injury: inhibition of late apoptosis and inflammation.

BACKGROUND: Complement has been implicated in the pathophysiology of renal ischemia-reperfusion (I/R) injury. However, the mechanism underlying complement-mediated renal I/R injury is thus far unknown. To investigate the involvement of complement in I/R injury, we studied the activation and deposition of complement in a murine model of renal I/R injury. Furthermore, we examined the effect of inhibition of complement-factor C5 on renal I/R injury. METHODS: Mice were subjected to 45 min of unilateral ischemia and subsequent contralateral nephrectomy and reperfusion for 2, 12, or 24 hr. Mice were control treated or treated with BB5.1, a monoclonal antibody that prevents cleavage of complement factor C5, thereby preventing C5a generation and formation of the membrane attack complex (MAC). RESULTS: Renal I/R induced extensive deposition of C3 early after reperfusion, whereas C6 and C9 deposition (MAC formation) occurred relatively late. I/R-induced complement deposition was mainly localized to tubular epithelium. Treatment with BB5.1 totally prevented MAC formation but also reduced C3 deposition. Inhibition of C5 strongly inhibited late inflammation, as measured by neutrophil influx and induction of the murine CXC chemokines macrophage inflammatory protein-2, KC, and lipopolysaccharide-induced CXC chemokine. Anti-C5 treatment furthermore abrogated late I/R-induced apoptosis, whereas early apoptosis was not affected. Moreover, BB5.1 treatment significantly protected against I/R-induced renal dysfunction. CONCLUSIONS: Renal I/R is followed by activation of the complement system and intrarenal deposition of C3 and MAC. Complement activation plays a crucial role in the regulation of inflammation and late apoptosis. Complement inhibition, by preventing C5 activation, abrogates late apoptosis and inflammation, being strongly protective against renal function loss.

Animals↗
PubMed1994

The role of complement in the pathogenesis of postpartum thyroiditis.

Postpartum thyroiditis (PPT) affects half of the 10% of women who have elevated circulating thyroid autoantibodies during the postpartum year. Because of the similarities between PPT and Hashimoto's thyroiditis, the pathogenic role of complement in PPT has been investigated. Complement fixation by thyroid peroxidase antibodies (TPO Abs) (expressed as log reciprocal titer) in serum from euthyroid TPO Ab-positive women (n = 29) was 0.91 at 1 month postpartum and increased to 1.45 by 12 months postpartum; complement C3 activation, measured by enzyme-linked immunosorbent assay, in a similar group of women (n = 75) was 0.05 at delivery and increased to 0.33 by 6 months postpartum. In women with PPT, there was greater TPO Ab-related complement activation during the postpartum year; complement fixation increased from 1.00 at 1 month postpartum to 1.48 at 4 months postpartum (P < 0.005) (n = 25), and C3 activation increased from 0.11 at delivery to 0.63 at 6 months postpartum (P < 0.005) (n = 73). Bioactive TPO Ab (TPO Ab x C3 index) was significantly higher in PPT women (55 kilo international units of activity (kIU)/L at 6 months postpartum) (Hashimoto range, 30-108 kIU/L) compared with euthyroid TPO Ab-positive women (< 9 kIU/L at all time points; P < 0.005). Serum samples from TPO Ab-negative control women showed no interaction with complement in either assay at any time during the postpartum year (complement fixation < 0.7; complement C3 activation index < 0.01). This detailed examination of the role of complement in the pathogenesis of PPT shows that TPO Ab-driven complement fixation is a marker for thyroid dysfunction in TPO Ab-positive women. The levels of bioactive TPO Ab in PPT fall within the range seen in Hashimoto's thyroiditis, suggesting similarities in their pathology.

Autoantibodies↗
PubMed2005

Intrinsic resistance of hepatocytes to complement-mediated injury.

When activated on or in the vicinity of cells, complement usually causes loss of function and sometimes cell death. Yet the liver, which produces large amounts of complement proteins, clears activators of complement and activated complexes from portal blood without obvious injury or impaired function. We asked whether and to what extent hepatocytes resist injury and loss of function mediated by exposure to complement. Using cells isolated from porcine livers as a model system, we found that, in contrast to endothelial cells, hepatocytes profoundly resist complement-mediated lysis and exhibit normal synthetic and conjugative functions when complement is activated on their surface. The resistance of hepatocytes to complement-mediated injury was not a function of cell surface control of the complement cascade but rather an intrinsic resistance of the cells dependent on the PI3K/Akt pathway. The resistance of hepatocytes to complement might be exploited in developing approaches to the treatment of hepatic failure or more broadly to the treatment of complement-mediated disease.

Animals↗
PubMed2006

Retrovirus-mediated over-expression of decay-accelerating factor rescues Crry-deficient erythrocytes from acute alternative pathway complement attack.

Decay-accelerating factor (DAF) and complement receptor 1-related gene/protein y (Crry) are two membrane-bound complement regulators on murine erythrocytes that inhibit C3/C5 convertases. Previously, we found that Crry- but not DAF-deficient erythrocytes were susceptible to alternative pathway complement-mediated elimination in vivo. To determine whether it is a unique activity or a higher level expression of Crry makes it indispensable on murine erythrocytes, we over-expressed DAF on Crry-deficient (Crry(-/-)) erythrocytes by retroviral vector-mediated DAF gene transduction of bone marrow stem cells. DAF retrovirus-transduced erythrocytes expressed 846 +/- 127 DAF molecules/cell (DAF(high)) compared with 249 +/- 94 DAF molecules/cell (DAF(low)) and 774 +/- 135 Crry molecules/cell on control mouse erythrocytes. DAF(high)-Crry(-/-) erythrocytes were significantly more resistant than either DAF(low)-Crry(-/-), DAF(-/-) -Crry(+/+) or wild-type erythrocytes to classical pathway complement-mediated C3 deposition in vitro. Furthermore, increased DAF expression rescued Crry(-/-) erythrocytes from acute alternative pathway complement attack in vivo. Notably, long term monitoring revealed that DAF(high)-Crry(-/-) erythrocytes were still more susceptible than wild-type erythrocytes to complement-mediated elimination as they had a shorter half-life in complement-sufficient mice but survived equally well in complement-deficient mice. These results suggest that both a high level expression and a more potent anti-alternative pathway complement activity of Crry contributed to its indispensable role on murine erythrocytes. Additionally, they demonstrate the feasibility of using stem cell gene therapy to correct membrane complement regulator deficiency on blood cells in vivo.

Animals↗
PubMed1991

Characterization of a Trypanosoma cruzi C3 binding protein with functional and genetic similarities to the human complement regulatory protein, decay-accelerating factor.

Evasion of the complement system by microorganisms is an essential event in the establishment of infection. In the case of Trypanosoma cruzi, the causative agent of Chagas disease, resistance to complement-mediated lysis is a developmentally regulated characteristic. Infectious trypomastigotes are resistant to complement-mediated lysis in the absence of immune antibodies, whereas the insect forms (epimastigotes) are sensitive to lysis via the alternative complement pathway. We have purified a developmentally regulated, trypomastigote glycoprotein, gp160, and shown that it has complement regulatory activity. The T. cruzi gp160 restricts complement activation by binding the complement component C3b and inhibiting C3 convertase formation. The protein is anchored in the parasite membrane via a glycosyl phosphatidylinositol linkage, similar to the human complement regulatory protein, decay-accelerating factor. Using anti-gp160 antibodies we have isolated a bacteriophage lgt11 clone expressing a portion of the gp160 gene that shares significant DNA sequence homology with the human DAF gene. These results provide functional, biochemical, and genetic evidence that the T. cruzi gp160 is a member of the C3/C4 binding family of complement regulatory proteins, and that gp160 may provide the infectious trypomastigotes with a means of evading the destructive effects of complement.

Animals↗
PubMed1991

In vitro activation of human complement by nitrogen bubbles.

Complement activation may be responsible for some of the symptoms of decompression sickness. In the present study, complement activation was studied by exposing human sera with or without red blood cells to nitrogen bubbles. Nitrogen bubbles activated human complement as measured by generation of the fluid-phase, complement-split product C5a des Arg. In addition, we found that complement activation continued after exposure to bubbles was stopped. This continued complement activation may explain the failure of recompression treatment in some patients. Complement activation induced by nitrogen bubbles in human sera was enhanced when red cells were present. Red cells may be able to provide a stable membrane surface on which complement activation by bubbles can occur more efficiently. Complement activation by nitrogen bubbles in serum also led to the binding of activated C3 to red cells. Quantitation of bystander red-cell-bound C3d may allow the assessment of complement activation occurring by nitrogen bubbles in individuals undergoing decompression.

Complement Activation↗
PubMed1989

Relative contributions of chemo-attractant and terminal components of complement to anti-glomerular basement membrane (GBM) glomerulonephritis.

The relative contributions of chemo-attractant and terminal components of complement to heterologous phase glomerular injury was studied in anti-GBM glomerulonephritis in rabbits. Normal rabbits (complement intact) were given anti-GBM antibody at a dose which resulted in 140 micrograms specific kidney-fixed antibody per gram of renal cortex, and developed significant proteinuria (1910 +/- 327 mg/24 h; control 18.2 +/- 6.1 mg/24 h; P less than 0.01). Leucocyte depletion significantly reduced but did not abolish proteinuria (574 +/- 186 mg/24 h, P less than 0.05). Complement depletion of neutrophil-depleted rabbits resulted in a further significant reduction in proteinuria 50.1 +/- 12.2 mg/24 h, P less than 0.05; versus neutrophil-depleted, complement-intact rabbits), indicating that both neutrophil accumulation and complement activation independent of neutrophils contribute to injury in this model. Rabbits congenitally deficient in the sixth component of complement (C6D) developed similar levels of proteinuria (2099 +/- 796 mg/24 h) to normal rabbits given an identical dose of antibody. However, after leucocyte depletion, C6D rabbits developed significantly less proteinuria (135 +/- 56 mg/24 h) than did leucocyte-depleted, complement-intact rabbits (P less than 0.05). These studies show that terminal complement components are not necessary for the full expression of acute anti-GBM antibody-initiated injury in leucocyte-intact rabbits. However, in the absence of leucocytes, C6 and the terminal complement components are apparently responsible for the majority of the complement-dependent glomerular injury.

Animals↗
PubMedDate not supplied

The role of complement in urticaria and angioedema.

Complement may play a primary or exacerbating factor in the production of urticaria and/or angioedema. As we have seen, the absence of inhibitor proteins, such as ClINH, C3bINA, or Carboxypeptidase N Anaphylatoxin Inactivator) can permit small amounts of active complement fragments, liberated "normally" through the action of nonspecific effector pathways, to produce generalized urticaria or angioedema. Abnormal degrees of complement activation, produced by circulating immune complexes, cryoglobulins, paraproteins, may also cause angioedema and/or urticaria. Autoimmune diseases, lymphoreticular malignancy, infections, drug reactions, and syndromes currently termed idioipathic may be associated with urticaria and angioedema due to pathologic complement activation. Direct effects of complement on blood vessels, either by anaphylatoxins or by the deposition of complement fixing immune complexes, may produce the vascular permeability requisite to these syndromes. Secondary effects, produced by the recruitment of inflammatory cells and/or the liberation of other vasoactive mediators from these cells may also occur. Finally, complement may act in a potent synergistic fashion with mediators such as prostaglandins to produce vascular permeability. Current studies, using antigenic, hemolytic, and immunofluorescent techniques for detecting complement involvement have identified a relatively limited number of syndromes in which complement is involved. It is anticipated that the use of more sensitive assays for anaphylatoxins, such as radioimmunoassay, neutrophil aggregation, and others, coupled with an understanding of the potential synergism between these and other mediators, will lead to the recognition of a wider role for complement in urticaria and angioedema.

Angioedema↗
PubMed1988

Detection of the terminal complement complex in patient plasma following acute myocardial infarction.

The mechanisms of inflammation responsible for the myocardial tissue damage seen after an acute myocardial infarction (AMI) have not been clearly identified. Recent lines of evidence, demonstrating depressed sera levels of individual complement components in patients after myocardial infarction, have suggested involvement of the complement (C) system in micro- and macrovascular injury subsequent to AMI. The present study assessed the role of complement as a mediator of myocardial inflammation by quantifying products of complement activation including, the terminal complement complex (TCC) the cytolytic component of the complement system, C1rC1s-C1 inhibitor complex and C3bBbP complex, formed following activation of the classical and alternative pathway, respectively, and anaphylatoxins C3a and C5a in 41 patients following AMI. Plasma TCC and C1rC1s-C1 inhibitor complex concentrations increased up to 32-fold (P less than 0.001) and 8-fold (P less than 0.001), respectively, while the C3bBbP complex, C3a des-Arg and C5a des-Arg each increased over 2-fold (P less than 0.001) 16 h after AMI, and were only minimally detectable during non-inflammatory myocardial conditions. Furthermore, TCC concentrations increased over 150% (P less than 0.001) one day after patients reinfarcted, subsequent to hospitalization for a primary AMI. These results demonstrate activation of complement after AMI and suggest that inflammatory mediators of the complement system may contribute to myocardial tissue damage during the infarction process.

Adult↗
PubMed1995

Regulation of the function of the first component of complement by human C1q receptor.

A membrane-associated receptor for the C1q subcomponent of complement is widely distributed among different cell types. While a number of possible physiological functions of the C1q receptor (C1qR) on different cell types have been described, the way in which C1qR regulates complement activity remains unclear. This report describes the mechanism by which C1qR regulates activation of the first component of complement, C1. Using purified components of complement, we were able to show that membrane-associated C1qR as well as detergent-solubilized C1qR, purified from polymorphonuclear leukocytes, human umbilical vein endothelial cells or an endothelial cell line, EA.hy 926, are able to inhibit complement-mediated lysis of C1q-sensitized erythrocytes. Using hemolytic assays, we were able to demonstrate that C1qR prevents the association of C1q with C1r and C1s to form macromolecular C1. In addition, incubation of C1qR with the collagen-like stalks, but not with the globular heads of C1q, inhibits the effect of C1qR. This demonstrates that C1qR exerts its complement inhibitory effect by binding to the collagen-like stalk of C1q. No complement regulatory effect of C1qR was observed on preformed macromolecular C1. These data suggest that besides such-well-known complement regulatory molecules as CD55 (DAF), CD46 (MCP), CD35 (CR1) and CD59 (HRF), C1qR too is able to regulate complement activity.

Carrier Proteins↗
PubMed1995

Evidence for activation of the terminal pathway of complement and upregulation of sulfated glycoprotein (SGP)-2 in the hypoglossal nucleus following peripheral nerve injury.

In a previous study, we found immunoreactivity for complement factors C3, C3d, and C4d, as well as endogenous IgG in the hypoglossal nucleus following hypoglossal nerve transection, suggesting that activation of the complement cascade had taken place in the vicinity of the axotomized motorneurons. In the present study, we found increased immunoreactivity for complement factor C1 and C1q in reactive microglia, indicating an increased potential for initiation of the classical pathway by binding of IgG to C1q. Furthermore, we found immunoreactivity for C9, which contributes to the formation of C5b-9, the final lytic product of the complement cascade close to the axotomized neurons and perineuronal glia. In addition, immunoreactivity and mRNA labeling of sulfated glycoprotein (SGP-2), a putative complement inhibitor, was increased in a subpopulation of the axotomized motorneurons. SGP-2 immunoreactivity was also increased in astroglial cells ipsilateral to the nerve injury. The results lend further support to the hypothesis that the complement cascade is activated in the vicinity of axotomized neurons, which in turn may be protected by complement inhibitors. The balance between activation of complement and complement inhibitors might have an impact on the degenerative components of the axon reaction and, in particular, the events leading to nerve cell death.

Animals↗
PubMed2000

Oligodendroglia are protected from antibody-mediated complement injury by normal immunoglobulins ("IVIg").

High-dose intravenous immunoglobulin (IVIg) treatment has become a promising immune therapy that can modulate the immune system at several levels, including the complement cascade. In relation to inflammatory demyelinating disease, there is some clinical evidence for the suppression of disease activity by IVIg, while a role in promoting remyelination after experimental myelin damage has been described. Antibody and complement deposition have been implicated in the immune attack in some cases of multiple sclerosis (MS), and to investigate the mechanisms of action of IVIg, we studied the effect of IVIg using the model of complement-mediated cell injury on oligodendroglia in vitro. There was no effect on direct complement lysis of the oligodendroglial cell line CG4, but antibody-dependent complement damage was inhibited in a dose-dependent manner by IVIg. These results were confirmed with primary cultures of oligodendrocyte precursor cells (OPC) and oligodendrocytes. The addition of excess C1, C3, and C4 did not influence the inhibitory effect of IVIg, implying that binding of these complement components does not play a role, in contrast to other experimental models of complement damage. F(ab')2 immunoglobulin fragments were at least partially responsible for the effect. We conclude that IVIg may be protective in antibody-mediated complement injury of oligodendrocytes and their progenitors, and that this effect is likely to be mediated via antibody binding, rather than interference with complement activation. Inhibition of inflammatory mechanisms, as opposed to a direct effect on remyelinating cells, may underlie the role of IVIg in promoting myelin repair in experimental models.

Animals↗