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PubMed1995

Down-regulation of CD59 (protectin) expression on human colorectal adenocarcinoma cell lines by levamisole.

The vulnerability of tumour cells to complement-mediated immune attack is regulated by membrane associated molecules. Recently, we have shown that the expression of the membrane attack complex inhibitor CD59 is enhanced on colonic adenocarcinoma cells compared to normal colonic epithelial cells. CD59 was shown, in the same study, to protect the tumour cells from complement-mediated lysis. Levamisole (LMS), used in conjunction with 5-fluorouracil as adjuvant therapy, reduces the incidence of colon cancer relapse following surgical resection. This led to our investigation of the effect of LMS on CD59 expression and function on the human colorectal cell lines HT29 and Caco-2. When cultured in the presence of 10 microM LMS, the cells reduced their expression of CD59 in a time-dependent manner. LMS treated HT29 cells were more sensitive to lysis by complement than control cells, and the reduction in CD59 expression was shown to be partly responsible for this. A reduction in CD59 expression will augment complement-mediated immune surveillance and may contribute to LMSs anti-tumour activity in vivo.

Adenocarcinoma↗
PubMed1991

Human serum induced opsonization of immunoglobulin G-coated polystyrene microspheres with complement components C3 and C4 as measured by flow cytometry.

Human IgG-coated polystyrene microspheres (IgG-ms) were incubated with human serum followed by biotinylated monoclonal anti-C3d or anti-C4d antibody, and phycoerythrin-streptavidin. The intensity of fluorescence was measured by flow cytometry and corresponds to the amount of deposited C3 and C4. Binding of C3 and C4 was dependent on the activation of the classical pathway of complement and on the amount of IgG adsorbed to the particles. No deposition was observed on control particles coated with bovine serum albumin or ovalbumin. Incubation of constant amounts of IgG-ms with increasing amounts of normal human serum (NHS) resulted in a dose-dependent increase in C3 deposition. The same result was found for C4 deposition at moderate NHS dilutions, but less C4 was detectable using a higher input of NHS. Half-maximum C3 and C4 deposition was observed at a mean serum dilution of 1/114 and 1/520, respectively (n = 26). No correlation was found between C4 or C3 deposition and either total C4 and C3 serum concentrations as measured by nephelometry or complement-mediated lysis of antibody-coated sheep red blood cells. Reduced or absent C4 or C3 deposition was found in the sera of patients with low amounts or deficiencies of components involved early in classical complement pathway activation whereas essentially normal C4 or C3 deposition was obtained with the sera of patients with deficiencies in components of the membrane attack complex. With this simple and specific functional assay using stable reagents an altered function of early components of the classical pathway of complement may be quickly and reliably detected in routine diagnostic laboratories. Moreover, such opsonized and well characterized particles may be useful in assays of phagocytic cell function.

Complement C3↗
PubMed1996

Characterization of transgenic pigs expressing functionally active human CD59 on cardiac endothelium.

The critical shortage of human donor organs has generated interest in the potential for porcine to human xenotransplantation. The initial immunological barrier to xenotransplantation is hyperacute rejection, which is mediated by xenoreactive antibodies and complement, and results in rapid and irreversible tissue destruction. While endogenous complement regulatory proteins (CRPs) protect cells from injury caused by autologous complement, they are relatively species specific and most likely ineffectual in this setting. This has led to the hypothesis that expression of human CRPs in transgenic pigs may affect susceptibility to complement-mediated tissue injury in a porcine-to-human xenograft. Using specific lines of transgenic pigs that express low levels of human CD59, a CRP that acts at the terminal stage of the complement cascade, we present evidence that shows that the human CD59 protein inhibits membrane attack complex assembly and reduces tissue damage when the heart is transplanted to a baboon. Examination by immunohistochemistry of transgenic porcine hearts after transplantation revealed markedly reduced deposition of C5b and MAC, but a similar level of C3 deposition as compared with transplanted control hearts. This finding supports the concept that the species specific function of CRPs contributes to the humoral barrier to xenotransplantation and, given the low level of human CD59 protein expression in the porcine heart, argues that the human protein contributes a unique rather than an additive function in regulation of complement in a xenogeneic setting.

Animals↗
PubMed1988

Activation of complement in IgA nephropathy.

Considerable evidence supports a role for the complement system in the pathogenesis of IgA nephropathy (IgAN). The alternative pathway components C3 and properdin (P) and the membrane attack complex (C5b-9) are generally found in the mesangial deposits in IgAN, while the classical pathway components C1q and C4 are usually absent. This pattern of immunofluorescence staining for complement components suggests activation of the alternative and terminal pathways in most patients. Despite normal serum concentrations of C3 and other complement proteins, fragments generated by activation of C3, including iC3b, C3d, and iC3b-C3d neoantigen, and sometimes C4, are often detected in plasma. We found that the severity of the histologic changes in the renal biopsy specimens correlated with plasma iC3b-C3d neoantigen concentrations as measured by an enzyme-linked immunosorbent assay. However, no other clinical feature correlated with the plasma concentrations of this neoantigen.

Complement Activation↗
PubMed2000

Chronic low level complement activation within the eye is controlled by intraocular complement regulatory proteins.

PURPOSE: To explore the role of the complement system and complement regulatory proteins in an immune-privileged organ, the eye. METHODS: Eyes of normal Lewis rats were analyzed for the expression of complement regulatory proteins, membrane cofactor protein (MCP), decay-acceleration factor (DAF), membrane inhibitor of reactive lysis (MIRL, CD59), and cell surface regulator of complement (Crry), using immunohistochemistry, Western blot analysis, and reverse transcription-polymerase chain reaction (RT-PCR). Zymosan, a known activator of the alternative pathway of complement system was injected into the anterior chamber of the eye of Lewis rats. Animals were also injected intracamerally with 5 microl (25 microg) of neutralizing monoclonal antibody (mAb) against rat Crry (5I2) or CD59 (6D1) in an attempt to develop antibody induced anterior uveitis; control animals received 5 microl of sterile phosphate-buffered saline (PBS), OX-18 (25 microg), G-16-510E3 (25 microg), or MOPC-21 (25 microg). The role of complement system in antibody-induced uveitis was explored by intraperitoneal injection of 35 U cobra venom factor (CVF), 24 hours before antibody injection. Immunohistochemical staining and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with Western blot analysis were used to detect the presence of membrane attack complex (MAC) and C3 activation products, respectively, in normal and antibody-injected rat eyes. RESULTS: Complement activation product MAC was present in the normal rat eye, and intraocular injection of zymosan induced severe anterior uveitis. The complement regulatory proteins, MCP, DAF, CD59, and Crry, were identified in the normal rat eye. Soluble forms of Crry and CD59 were also detected in normal rat aqueous humor. Severe anterior uveitis developed in Lewis rats injected with a neutralizing mAb against Crry, with increased formation of C3 split products. Systemic complement depletion by CVF prevented the induction of anterior uveitis by anti-Crry mAb. Intracameral injection of anti-rat CD59 (6D1), anti-rat MHC class I antigen (OX-18), anti-rat Ig (G-16-510E3), or MOPC-21 caused no inflammatory reaction. CONCLUSIONS: The results suggest that the complement system is continuously active at a low level in the normal eye and is tightly regulated by intraocular complement regulatory proteins.

Animals↗
PubMed1993

Differential expression of the complement regulatory proteins in the human eye.

PURPOSE: The presence of complement activation products in the human eye during infection or inflammation has been well described. During complement activation the host must be protected from attack against self tissue; this is achieved by three membrane-bound complement regulatory proteins: membrane cofactor protein (MCP, CD46), decay accelerating factor (DAF, CD55), and membrane attack complex inhibiting protein (CD59). This study was undertaken to analyze the expression of these proteins in the normal human eye. METHODS: Tissues were sectioned by cryostat and both polyclonal and monoclonal antibodies to MCP, DAF, and CD59 were used. Control stains were performed with nonrelevant antibodies of the same immunoglobulin subclass and normal rabbit serum as well as by omission of the primary and secondary antibodies. RESULTS: All three proteins were found to be differentially expressed in the human eye. With anti-MCP, strong staining of the corneal epithelium and weak staining of the corneal keratocytes in stroma and photoreceptor cells was observed. Staining with anti-DAF was very strong in the corneal epithelium and the ciliary body and moderate in the corneal stroma (keratocytes) and iris. In contrast, anti-CD59 stained very strongly in the corneal epithelium, corneal stroma (keratocytes), iris, choroid, and all layers of the retina, and moderately in the ciliary body. CONCLUSIONS: Identification of MCP, DAF, and CD59 in the human eye provides evidence that a regulatory system exists to protect these cells from destruction by complement-activating events. It remains to be determined if other more specialized functions exist for these proteins, especially in the case of CD59 because of its extensive expression in the retina.

Adult↗
PubMed1988

Studies on the formation of a unique cellular intermediate (EAC14256) from EAC142 and C56.

The binding reaction of C56 to EAC142 was studied. The following was observed: (1) C56 can bind to EAC142, without participation of C3 or C7, to form EAC14256; (2) the efficiency of EAC14256 formation from EAC142 and C56 depends highly on the ionic strength of the buffer; (3) EAC14256, generated from EAC142 and C56, decays spontaneously by elution of C56 into the medium and thus the reaction between C56 and EAC142 is reversible; (4) the receptor on EAC142 for C56 is C2 or C42 on the cell surface, and (5) the binding of C56 to C2 or C42 on cells is independent of the usual (C3-dependent) complement cascade activation. These observations, together with the results of our previous report, indicate that the binding of C56, generated from the activation of C5 by C42 (without C3), to EAC142 may be the initial step of membrane attack complex formation in C3-independent immune hemolysis.

Antibodies↗
PubMed1986

Demonstration of C3b receptor-like activity and of decay-accelerating factor-like activity on rabbit erythrocytes.

C3b receptor activity and decay-accelerating activity for the C3 convertase, C3b,Bb, were demonstrated on rabbit erythrocytes (ERAB). Particles bearing C3b agglutinated ERAB if the C3b was of rabbit origin, but not if it was of human origin. The reactivity of rabbit C3b was abolished by enzymatic conversion of C3b to C3bi. Deposited on ERAB, rabbit C3b, but not human C3b, was cleaved by factor I in the absence of factor H. Similarly, decay acceleration of the C3b,Bb complex on ERAB occurred when the complex was of rabbit origin, but not when it was of human origin. Soluble immune complexes in the presence of rabbit serum were bound to and then released from the ERAB. Binding of the complexes is presumed to be mediated by immune complex-bound C3b and release to be the consequence of degradation of C3b by Factor I. These findings suggest that ERAB, like human erythrocytes, are endowed with membrane-associated complement regulators that protect these cells against homologous complement attack and participate in the clearing mechanism of circulating immune complexes.

Animals↗
PubMed1997

Mutational analysis of the active site and antibody epitopes of the complement-inhibitory glycoprotein, CD59.

The Ly-6 superfamily of cell surface molecules includes CD59, a potent regulator of the complement system that protects host cells from the cytolytic action of the membrane attack complex (MAC). Although its mechanism of action is not well understood, CD59 is thought to prevent assembly of the MAC by binding to the C8 and/or C9 proteins of the nascent complex. Here a systematic, structure-based mutational approach has been used to determine the region(s) of CD59 required for its protective activity. Analysis of 16 CD59 mutants with single, highly nonconservative substitutions suggests that CD59 has a single active site that includes Trp-40, Arg-53, and Glu-56 of the glycosylated, membrane-distal face of the disk-like extra-cellular domain and, possibly, Asp-24 positioned at the edge of the domain. The putative active site includes residues conserved across species, consistent with the lack of strict homologous restriction previously observed in studies of CD59 function. Competition and mutational analyses of the epitopes of eight CD59-blocking and non-blocking monoclonal antibodies confirmed the location of the active site. Additional experiments showed that the expression and function of CD59 are both glycosylation independent.

Amino Acid Sequence↗
PubMed1996

Effector mechanisms in demyelinating neuropathies.

While the cause of the immune-mediated neuropathies (Guillain-Barr-e syndrome, GBS; CIDP; multi-focal motor neuropathy and paraproteinemic neuropathies) remains elusive considerable progress has been made in delineating the effector mechanisms that underlie myelin destruction. In GBS circulating antibodies to glycolipids possibly precipitated by an antecedent Campylobacter jejuni infection can be detected with high frequency. These antibodies may interfere with neuromuscular transmission and eventuate myelin damage by activating the complement system, providing for the generation of chemotactically active split products C3a and C5a, the opsonin C3b, and assembly of the membrane attack complex. Such antibodies may also, via binding to the Fc receptor, target macrophages to the myelin sheath. Corroborative evidence for a crucial pathogenic role of antibody-mediated complement activation is also available for the MAG-associated neuropathies. Macrophages as decisive effector cells of myelin damage may also act by releasing injurious molecules such as oxygen radicals, nitric oxide metabolites, proteases, eicosanoids and cytokines. Demyelinative as well as degenerative actions have been described for the cytokines TNF-alpha and lymphotoxin. Increased understanding of the effector mechanisms underlying demyelination may aid in developing more efficacious treatments for this group of neuropathies.

Autoantibodies↗
PubMed1999

Can we learn from the pathogenetic strategies of group A hemolytic streptococci how tissues are injured and organs fail in post-infectious and inflammatory sequelae?

The purpose of this review-hypothesis is to discuss the literature which had proposed the concept that the mechanisms by which infectious and inflammatory processes induce cell and tissue injury, in vivo, might paradoxically involve a deleterious synergistic 'cross-talk', among microbial- and host-derived pro-inflammatory agonists. This argument is based on studies of the mechanisms of tissue damage caused by catalase-negative group A hemolytic streptococci and also on a large body of evidence describing synergistic interactions among a multiplicity of agonists leading to cell and tissue damage in inflammatory and infectious processes. A very rapid cell damage (necrosis), accompanied by the release of large amounts of arachidonic acid and metabolites, could be induced when subtoxic amounts of oxidants (superoxide, oxidants generated by xanthine-xanthine oxidase, HOCl, NO), synergized with subtoxic amounts of a large series of membrane-perforating agents (streptococcal and other bacterial-derived hemolysins, phospholipases A2 and C, lysophosphatides, cationic proteins, fatty acids, xenobiotics, the attack complex of complement and certain cytokines). Subtoxic amounts of proteinases (elastase, cathepsin G, plasmin, trypsin) very dramatically further enhanced cell damage induced by combinations between oxidants and the membrane perforators. Thus, irrespective of the source of agonists, whether derived from microorganisms or from the hosts, a triad comprised of an oxidant, a membrane perforator, and a proteinase constitutes a potent cytolytic cocktail the activity of which may be further enhanced by certain cytokines. The role played by non-biodegradable microbial cell wall components (lipopolysaccharide, lipoteichoic acid, peptidoglycan) released following polycation- and antibiotic-induced bacteriolysis in the activation of macrophages to release oxidants, cytolytic cytokines and NO is also discussed in relation to the pathophysiology of granulomatous inflammation and sepsis. The recent failures to prevent septic shock by the administration of only single antagonists is disconcerting. It suggests, however, that since tissue damage in post-infectious syndromes is caused by synergistic interactions among a multiplicity of agents, only cocktails of appropriate antagonists, if administered at the early phase of infection and to patients at high risk, might prevent the development of post-infectious syndromes.

Animals↗
PubMed1996

The multidrug resistance phenotype confers immunological resistance.

Multidrug resistance (MDR), which is due, in part, to the overexpression of P-glycoprotein, confers resistance to a variety of natural product chemotherapeutic agents such as daunorubicin, vincristine, and colchicine. RV+ cells are a P-glycoprotein overexpressing variant of the HL60 myeloid leukemia cell line. In addition to classic MDR, RV+ cells displayed relative resistance to complement-mediated cytotoxicity with both immunoglobulin G and M antibodies against different cell surface antigens, but not to antibody-dependent cellular cytotoxicity and lymphokine-activated killing. Complement resistance was reversed both by treatment with verapamil and with specific monoclonal antibodies (mAbs) capable of binding to P-glycoprotein and blocking its function. To further confirm that the resistance of RV+ cells was not a consequence of the selection of the cells on vincristine, a second system involving P-glycoprotein infectants was also investigated. K562 cells infected with the MDR1 gene, which were never selected on chemotherapeutic drugs, also displayed relative resistance to complement-mediated cytotoxicity. This MDR1 infection-induced resistance was also reversed by mAbs that bind to P-glycoprotein. Therefore, the MDR phenotype as mediated by P-glycoprotein provides resistance to complement-mediated cytotoxicity. The increased intracellular pH and the decreased membrane potential due to the MDR phenotype may result in abnormal membrane attack complex function. This observation may have implications for the possible mechanisms of action of P-glycoprotein and for a possible physiologic role for P-glycoprotein in protection against complement-mediated autolysis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Mechanisms of cell death in Alzheimer disease--immunopathology.

Lesions in such chronic neurodegenerative disorders as Alzheimer disease, Parkinson disease, the parkinsonism dementia complex of Guam and amyotrophic lateral sclerosis have associated with them a variety of proteins known to be involved in inflammatory processes. This is particularly true of Alzheimer disease where inflammatory reactions are thought to be important contributors to the neuronal loss. They include complement proteins, complement inhibitors, acute phase reactants, inflammatory cytokines, proteases and protease inhibitors. Studies of cultured human astrocytes and microglia, obtained from postmortem brain, have established that nearly all of these proteins are produced by one or another of these cell types. Human neurons also produce many inflammatory proteins and their inhibitors, creating complex interactions. Accumulations of amyloid and extracellular tangles apparently act as irritants, causing the activation of complement, the initiation of reactive changes in microglia, and the release of potentially neurotoxic products. Such products include the membrane attack complex, oxygen free radicals and excess glutamate. Twenty epidemiological studies that have been published to data indicate that populations taking antiinflammatory drugs have a significantly reduced prevalence of Alzheimer disease or a slower mental decline. One small clinical trial with indomethacin showed arrest of the disease over a 6 month period. Therapeutic intervention in key inflammatory processes holds great promise for the amelioration of Alzheimer disease and possibly other neurodegenerative disorders.

Alzheimer Disease↗
PubMed1998

The importance of inflammatory mechanisms in Alzheimer disease.

Lesions in such chronic neurodegenerative disorders as Alzheimer disease (AD), Parkinson disease, the parkinsonism dementia complex of Guam, and amyotrophic lateral sclerosis have associated with them a variety of proteins known to be involved in inflammatory processes. This is particularly true of AD, where inflammatory reactions are thought to be important contributors to the neuronal loss. Proteins present include complement proteins, complement inhibitors, acute phase reactants, inflammatory cytokines, proteases, and protease inhibitors. Studies of cultured human astrocytes and microglia, obtained from postmortem brain, have established that nearly all of these proteins are produced by one or another of these cell types. Human neurons also produce many inflammatory proteins and their inhibitors, creating complex interactions. Accumulations of amyloid and extracellular tangles apparently act as irritants, causing the activation of complement, the initiation of reactive changes in microglia, and the release of potentially neurotoxic products. Such products include the membrane attack complex, oxygen free radicals, and excess glutamate. Twenty epidemiological studies that have been published to date indicate that populations taking antiinflammatory drugs have a significantly reduced prevalence of AD or a slower mental decline. One small clinical trial with indomethacin showed arrest of the disease over a six-month period. Therapeutic intervention in key inflammatory processes holds great promise for the amelioration of AD and possibly other neurodegenerative disorders.

Alzheimer Disease↗
PubMed2005

The extracellular matrix and inflammation: fibromodulin activates the classical pathway of complement by directly binding C1q.

Components that propagate inflammation in joint disease may be derived from cartilage since the inflammation resolves after joint replacement. We found that the cartilage component fibromodulin has the ability to activate an inflammatory cascade, i.e. complement. Fibromodulin and immunoglobulins cause comparable deposition of C1q, C4b, and C3b from human serum. Using C1q and factor B-deficient sera in combination with varying contents of metal ions, we established that fibromodulin activates both the classical and the alternative pathways of complement. Further studies revealed that fibromodulin binds directly to the globular heads of C1q, leading to activation of C1. However, deposition of the membrane attack complex and C5a release were lower in the presence of fibromodulin as compared with IgG. This can be explained by the fact that fibromodulin also binds complement inhibitor factor H. Factor H and C1q bind to non-overlapping sites on fibromodulin, but none of the interactions is mediated by the negatively charged keratan sulfate substituents of fibromodulin. C1q but not factor H binds to an N-terminal fragment of fibromodulin previously implicated to be affected in cartilage stimulated with the inflammatory cytokine interleukin 1. Taken together our observations indicate fibromodulin as one factor involved in the sustained inflammation of the joint.

Complement Activation↗
PubMed1998

Structure, distribution, and functional role of protectin (CD59) in complement-susceptibility and in immunotherapy of human malignancies (Review).

Protectin (CD59) is a glycosyl-phosphatidylinositol-anchored cell membrane glycoprotein, ubiquitously expressed, though to a different extent, on benign and malignant cells. CD59 inhibits complement (C)-mediated lysis of target cells by preventing the formation of the membrane attack complex, in the terminal step of C-activation. Recent experimental evidence demonstrates that CD59 is the main restriction factor of C-mediated lysis of malignant cells of different histotype. Additionally, a soluble form of CD59, that retains its anchoring ability and functional properties, has been most recently identified in body fluids and in culture supernatants of different malignant cells. In view of its functional role, CD59 may protect neoplastic cells from C-mediated lysis, contributing to their escape from innate C-control and to tumor progression; additionally, the expression of CD59 by neoplastic cells may contribute to impair the therapeutic efficacy of C-activating monoclonal antibodies (mAb) directed to tumor-associated antigens. In the light of the functional role of CD59, this review focuses on the structural features, tissue distribution and regulation of the expression of CD59 in malignant tissues, and on the foreseeable application(s) of CD59 to improve the therapeutic efficacy of clinical approaches of humoral immunotherapy with C-activating mAb in human malignancies.

CD59 Antigens↗
PubMed2005

F(ab')2 antibody fragments against Trypanosoma cruzi calreticulin inhibit its interaction with the first component of human complement.

Trypanosoma cruzi calreticulin (TcCRT), described in our laboratory, retains several important functional features from its vertebrate homologues. We have shown that recombinant TcCRT inhibits the human complement system when it binds to the collagenous portion of C1q. The generation of classical pathway convertases and membrane attack complexes is thus strongly inhibited. In most T. cruzi-infected individuals, TcCRT is immunogenic and mediates the generation of specific antibodies. By reverting the C1q / TcCRT interaction, a parasite immune evasion strategy, these antibodies contribute to the host/parasite equilibrium. In an in vitro correlate of this situation, we show that the Clq/TcCRT interaction is inhibited by F(ab')2 polyclonal anti-TcCRT IgG fragments. It is therefore feasible that in infected humans anti-TcCRT antibodies participate in reverting an important parasite strategy aimed at inhibiting the classical complement pathway. Thus, membrane-bound TcCRT interacts with the collagenous portion Clq, and this Clq is recognized by the CD91-bound host cell CRT, thus facilitating parasite internalization. Based on our in vitro results, it could be proposed that the in vivo interaction between TcCRT and vertebrate Clq could be inhibited by F(ab')2 fragments anti-rTcCRT or against its S functional domain, thus interfering with the internalization process.

Animals↗
PubMed2006

Protection by meningococcal outer membrane protein PorA-specific antibodies and a serogroup B capsular polysaccharide-specific antibody in complement-sufficient and C6-deficient infant rats.

The relative contributions of antibody-induced complement-mediated bacterial lysis and antibody/complement-mediated phagocytosis to host immunity against meningococcal infections are currently unclear. Further, the in vivo effector functions of antibodies may vary depending on their specificity and Fc heavy-chain isotype. In this study, a mouse immunoglobulin G2a (mIgG2a) monoclonal antibody (MN12H2) to meningococcal outer membrane protein PorA (P1.16), its human IgG subclass derivatives (hIgG1 to hIgG4), and an mIgG2a monoclonal antibody (Nmb735) to serogroup B capsular polysaccharide (B-PS) were evaluated for passive protection against meningococcal serogroup B strain 44/76-SL (B:15:P1.7,16) in an infant rat infection model. Complement component C6-deficient (PVG/c-) rats were used to assess the importance of complement-mediated bacterial lysis for protection. The PorA-specific parental mIgG2a and the hIgG1 to hIgG3 derivatives all induced efficient bactericidal activity in vitro in the presence of human or infant rat complement and augmented bacterial clearance in complement-sufficient HsdBrlHan:WIST rats, while the hIgG4 was unable to do so. In C6-deficient PVG/c- rats, lacking complement-mediated bacterial lysis, the augmentation of bacterial clearance by PorA-specific mIgG2a and hIgG1 antibodies was impaired compared to that in the syngeneic complement-sufficient PVG/c+ rat strain. This was in contrast to the case for B-PS-specific mIgG2a, which conferred similar protective activity in both rat strains. These data suggest that while anti-B-PS antibody can provide protection in the infant rats without membrane attack complex formation, the protection afforded by anti-PorA antibody is more dependent on the activation of the whole complement pathway and subsequent bacterial lysis.

Animals↗