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PubMed1978

Primary structural analysis of the polypeptide portion of human C5a anaphylatoxin. Polypeptide sequence determination and assignment of the oligosaccharide attachment site in C5a.

The C5a molecule is one of two spasmogenic fragments (i.e. C3a and C5a) released from serum components C3 and C5 during complement activation. These fragments are called anaphylatoxins because their ability to stimulate mast cell histamine release, smooth muscle contraction, and increased vascular permeability may lead to a fatal reaction resembling anaphylactic shock in experimental animals. In addition, the C5a molecule, which is a glycoprotein, is perhaps the most potent of all humoral chemoattractants for polymorphonuclear leukocytes. Most of the structural analyses in this study were performed on the desArg 74 form of human C5a (C5adesArg). C5adesArg represents a natural form of C5a that is recovered from activated serum when no inhibitors are added to block the action of serum carboxypeptidase. The complete primary structure of the human C5a polypeptide portion is reported here. A partial characterization of intact human C5a has been previously reported (Fernandez, H. N., and Hugli, T. E. (1976) J. Immunol. 117, 1688--1694). The polypeptide portion of C5a contains 74 amino acids, accounting for a molecular weight of 8,200 while the carbohydrate portion accounts for approximately 3,000. The carbohydrate portion of C5a exists as a single complex oligosaccharide unit attached to an asparagine at position 64. An unusual feature of the C5a molecule is its large content of half-cystine, which accounts for more than 9% of its total residues. Two repeating Cys sequences occur in the linear structure and 6 of the 7 half-cystines in C5a are located at nearly identical positions to those in the human C3a molecule. In fact, sequence similarities between C3a and C5a indicate their common genetic ancestry. The role of C5a and C5adesArg as chemotactic factors prompted comparisons of their structural features with those of the chemotactically active formyl-Met peptides (Schiffman E., Corcoran, B. A., and Wahl, S. M. (1975) Proc. Natl. Acad. Sci. U.S.A. 72, 1059--1062). Removal of the COOH-terminal arginyl residue from C5a reduces chemotactic activity; therefore, the terminal portion of this molecule appears to play an active role in stimulating leukocyte migration. Hence the COOH-terminal sequence of C5a was examined for structural similarities to that of the formyl-Met peptides. Since methionine assumes a special functional importance in the formyl-Met peptides, attention is focused on the single methionyl residue in C5a. This methionyl residue, located near the COOH terminus of the molecule, may play an active role in the functional expression of C5a as a chemotactic factor. Although human and pig C3a show a close structural and functional relationship to C5a they lack the ability to excite leukotaxis, and this difference may correlate with the absence of a methionyl residue near the COOH terminus of C3a.

Amino Acid Sequence↗

PubMed1974

Elastase of Pseudomonas aeruginosa: inactivation of complement components and complement-derived chemotactic and phagocytic factors.

A purified elastase from Pseudomonas aeruginosa was highly destructive for fluid-phase and cell-bound C1 and C3 and fluid-phase C5, C8, and C9. Inactivation of C4, C2, C6, and C7 by the enzyme varied from 0 to 67%. Low concentrations of elastase generated, then inactivated, a chemotactic factor from human C5 but not from C3. Higher enzyme concentrations inactivated the C5 chemotactic activity at a faster rate. Elastase treatment of sensitized pseudomonads containing cell-bound C3 reduced the phagocytic indexes of polymorphonuclear leukocytes. The data support the proposed chemopathogenic role of the elastase in generation of the characteristic non-inflammatory Pseudomonas vasculitis.

Animals↗

PubMed1989

Vitronectin colocalizes with Ig deposits and C9 neoantigen in discoid lupus erythematosus and dermatitis herpetiformis, but not in bullous pemphigoid.

C9 neoantigen immunoreactivity has been found to colocalize with C3 immunoreactivity at the dermal-epidermal junction zone (DEZ) in skin specimens from patients with bullous pemphigoid, lupus erythematosus and dermatitis herpetiformis. The present study was designed to elucidate whether the C9 neoantigen immunoreactivity represents deposition of membrane attack complexes or non-lytic SC5b-9 complexes. Skin specimens from 11 patients with pemphigoid, five patients with discoid lupus erythematosus and from nine patients with dermatitis herpetiformis were studied with immunofluorescence using both monoclonal and polyclonal antibodies against C9 neoantigen and against vitronectin (S-protein), an inhibitor to the membrane attack complex of complement. Specimens from the pemphigoid patients demonstrated C9 neoantigen reactivity along the DEZ without detectable colocalized vitronectin. This suggests deposition of membrane attack complexes in the pemphigoid lesions. Immunoreactivity of both C9 neoantigen and vitronectin was detected in the DEZ in specimens of discoid lupus erythematosus and in the tips of dermal papillae in specimens of dermatitis herpetiformis. The combined presence of C9 neoantigen- and vitronectin immunoreactivity may indicate deposition of C9 as part of the non-lytic SC5b-9 complex. The finding reported here of differential deposition of vitronectin and C9 in different diseases indicates that the presence of C9 neoantigen immunoreactivity in tissue per se does not represent the deposition of membrane attack complexes, but that it may also be C9 deposited as part of the nonlytic SC5b-9 complex.

Autoantigens↗

PubMed1982

The chemical mediation of delayed hypersensitivity skin reactions: III. Purification and characterization of a precursor protein for macrophage-chemotactic factor in normal guinea pig plasma.

A putative precursor protein for macrophage-chemotactic factor, which was extracted fro inflammatory skin sites (MCFS-1) (Kambara et al, Am J Pathol 1977, 87:359-374), was found in normal guinea pig plasma and was purified to an apparent homogeneity upon SDS-polyacrylamide gel electrophoresis with a molecular weight of 160,000. This plasma protein was different from complement components of C3 and C5 in terms of molecular weight, functional activity as complements detected by hemolytic assay, and immunologic properties. Although it exhibited the common antigenicity with MCFS-1, it did not show any chemotactic activity for macrophages, However, incubation of this plasma protein at either 4 C for 5 days or 37 C for 1-2 days could generate a chemotactic factor with a molecular weight of approximately 150,000 which was similar to that of MCFS-1. This generation of chemotactic activity was completely prevented by the presence of the serine-type protease inhibitor, phenylmethylsulfonyl fluoride. These data could be well accounted for if we assume that this plasma protein might be a precursor for the macrophage-chemotactic factor found in delayed hypersensitivity skin sites, and that a proteolytic process might be involved in the activation of this precursor.

Animals↗

PubMed1997

Complement activation in Henoch-Schönlein purpura.

The pathogenetic mechanism underlying Henoch-Schönlein purpura (HSP) is poorly understood. Complement activation has been thought to have a role, but despite the demonstration of complement components in skin and renal biopsy material, serological evidence of complement activation is not convincing. We have assessed complement activation in 64 children with acute HSP. We used an enzyme-linked immunosorbent assay to measure plasma levels of three multimolecular complement activation protein (CAP) complexes: C1r:C1s:C1-inhibitor, C3bP and C5b-9. We found no significant difference between the levels of CAPs in children with acute HSP and a control group of children. This study does not support a role for complement activation in the pathogenesis of HSP.

Adolescent↗

PubMed1983

Inhibitory activity of heated ewe serum for ewe and ram serum complement.

In the presence of an indicator antigen-antibody complex, the complement (C) activity in ewe and ram serum was reduced or abolished by addition of ewe serum that had been heated at 56 degrees C for 10 minutes. Pre-incubation of heated ewe serum at 39 degrees C for 30 minutes with the C source prior to addition of the indicator system or addition at the same time caused similar reductions in C activity. Results from the haemolytic, conglutinating and haemagglutinating activities studied indicate that the ewe serum inhibitor(s) reacts with activated classical or alternative activating pathway components and/or the third component of C (C3). The presence of a potent C inhibitor(s) in ewe serum probably accounts for the low sheep C titres with some assay systems. As the heated ewe serum did not appear to activate ewe or ram C per se, it is more appropriate to regard it as 'inhibitory' rather than 'anticomplementary'.

Journal Article↗

PubMed2006

Therapeutic activity of C5a receptor antagonists in a rat model of neurodegeneration.

The complement system is thought to be involved in the pathogenesis of numerous neurological diseases, although its precise role remains controversial. In this study we used orally active C5a receptor antagonists (PMX53 and PMX205) developed in our laboratories in a rat model of 3-nitropropionic acid (3-NP) -induced Huntington's disease. Administration of the C5a antagonists (10 mg/kg/day, oral) either 48 h pre- or 48 h post-toxin significantly reduced body weight loss, anorexia, and behavioral and motor deficits associated with 3-NP intoxication. Striatal lesion size, apoptosis, neutrophil infiltration, and hemorrhage were also significantly reduced in C5a antagonist-treated rats. Immunohistochemical analysis demonstrated marked deposition of C3 and C9, and up-regulation of C5a receptors on neuronal cells at the time of lesion formation. Inhibition of prostaglandins or TNF-alpha with ibuprofen or infliximab had no effect in this model. The C5a antagonists did not affect 3-NP-induced cell death when added directly to rat striatal neuronal cultures, indicating a secondary mechanism of action in vivo. Our findings demonstrate for the first time that complement activation in the brain, particularly C5a, is a key event in the pathogenesis of this disease model, and suggest a future role for inhibitors of C5a in the treatment of neurodegenerative diseases.

Animals↗

PubMed2006

Structure and regulatory profile of the monkeypox inhibitor of complement: comparison to homologs in vaccinia and variola and evidence for dimer formation.

The outbreak of monkeypox in the Unites States in the summer of 2003 was the first occurrence of this smallpox-like disease outside of Africa. This limited human epidemic resulted from cross-infection of prairie dogs by imported African rodents. Although there were no human fatalities, this outbreak illustrates that monkeypox is an emerging natural infection and a potential biological weapon. We characterized a virulence factor expressed by monkeypox (monkeypox inhibitor of complement enzymes or MOPICE). We also compared its structure and regulatory function to homologous complement regulatory proteins of variola (SPICE) and vaccinia (VCP). In multiple expression systems, 5-30% of MOPICE, SPICE, and VCP consisted of function-enhancing disulfide-linked homodimers. Mammalian cells infected with vaccinia virus also expressed VCP dimers. MOPICE bound human C3b/C4b intermediate to that of SPICE and VCP. Cofactor activity of MOPICE was similar to VCP, but both were approximately 100-fold less efficient than SPICE. SPICE and VCP, but not MOPICE, possessed decay-accelerating activity for the C3 and C5 convertases of the classical pathway. Additionally, all three regulators possessed heparin-binding capability. These studies demonstrate that MOPICE regulates human complement and suggest that dimerization is a prominent feature of these virulence factors. Thus, our data add novel information relative to the functional repertoire of these poxviral virulence factors. Furthermore, targeting and neutralizing these complement regulatory active sites via mAbs is a therapeutic approach that may enhance protection against smallpox.

Amino Acid Sequence↗

PubMed1987

Desensitization of macrophage oxygen metabolism on immobilized ligands: different effect of immunoglobulin G and complement.

During adhesion and spreading to immobilized immune complexes, casein-elicited mouse peritoneal macrophages produced superoxide anion. This production was time-dependent, ceased after a couple of hours, and was due to interaction with immunoglobulins G (IgG) because neither immobilized antigen alone nor immunoglobulins M with or without complement-derived fragments were efficient stimuli. Cultivation of macrophages on immobilized IgG for 24 hr caused desensitization of the response to an unrelated stimulus like zymosan. Desensitization was due neither to inhibition of binding and uptake of zymosan nor to alterations of NADPH oxidase. In fact, macrophages cultivated on immobilized IgG bound and internalized zymosan and responded to PMA with production of superoxide anion normally. Desensitization was not specific for casein-elicited macrophages because both resident peritoneal and Corynebacterium parvum-activated macrophages underwent desensitization if cultivated for 24 hr on immobilized immune complexes. Desensitization on immobilized IgG was maximal after 24 hr, lasted up to 3 days in culture, and was reversed by detaching macrophages from the IgG surface and further cultivating them in normal tissue culture plastic. Scavengers of products of the oxygen metabolism such as superoxide dismutase and catalase and inhibitors of arachidonic acid metabolism such as indomethacin and nordihydroguaiaretic acid did not prevent desensitization. In addition, the zymosan-stimulated release of arachidonic acid was suppressed after cultivation on immobilized IgG for 24 hr; also in this case, the response to PMA was conserved. Contrary to cultivation on immobilized IgG, cultivation of macrophages on fragments derived from C3 was not accompanied by desensitization of the response to zymosan. These results indicate that although the interaction of Fc receptors with their ligands does not impair binding and uptake of zymosan, alterations in the sequence of signals which leads to the activation of the oxygen metabolism can occur, causing a complete dissociation between phagocytosis and stimulation of the oxygen metabolism.

Animals↗

PubMed1994

Kinetic characterization of phosphoenolpyruvate carboxylase extracted from whole-leaf and from guard-cell protoplasts of Vicia faba L. (C3 plant) with respect to tissue pre-illumination.

Whole leaves and guard-cell protoplasts of the C3 plant Vicia faba L. (broad bean) were separately extracted following a period of illumination or following a period of darkness. Kinetic parameters of phosphoenolpyruvate carboxylase (PEPC, EC 4.1.1.31), Vmax and Km(PEP.Mg), were determined as a function of assay pH (7.0 or 8.1), the presence of 5 mM glucose-6-Pfree (Glc-6-P, an activator), and the presence of 5 mM malatefree (an inhibitor). On the basis of these parameters, guard-cell PEPC was distinguished from that of whole leaf, indicating either that guard cells contain a unique isoenzyme of PEPC or a different complement of isoenzymes or--and less likely--that the obligatorily different methodologies for the leaf (intact organ) and the guard-cell (protoplast) enzymes altered them specifically. The values of Vmax were relatively unchanged, regardless of assay conditions or tissue pretreatment. The values obtained for whole-leaf PEPC Vmax were restricted to a small range (52.4 +/- 5.9 (SD) to 64.4 +/- 4.8 (SD) mumol.g fresh mass-1.h-1; the high value coincided with the presence of Glc-6-P, and the low value was obtained in the presence of malate. Guard-cell PEPC Vmax was also restricted to a small range: 7.48 +/- 0.89 (SD) pmol.guard-cell pair-1.h-1 (pH 8.1, light, +Glc-6-P) to 5.79 +/- 0.60 (SD) pmol.guard-cell pair-1.h-1 (pH 7.0, dark, +malate). Depending on effectors, and particularly pH, large changes in Km(PEP.Mg) were calculated (whole-leaf PEPC: 0.03 to 3.84 mM; guard-cell PEPC: 0.06 to 3.43 mM).(ABSTRACT TRUNCATED AT 250 WORDS)

Fabaceae↗

PubMed2000

Antidepressant treatment during social challenge prior to 1 year of age affects immune and endocrine responses in adult macaques.

Antidepressants are widely used in treating depression and other behavioral problems in children and adolescents. Little is known about the long-term effects of these agents, particularly on physiological systems. The effects of previous antidepressant treatment during a social challenge in 9-month-old rhesus monkeys (Macaca mulatta) on their adult immune and endocrine responses were studied. Prior to the social challenge, the monkeys were reared either by their mother or in a peer group. Monkeys were treated with either a serotonergic agonist (fluoxetine), a noradrenergic agonist (desipramine), or saline during social separation. Non-separated, saline-treated monkeys served as control monkeys. In order to evaluate immune effects of early antidepressant treatment, adult monkeys were immunized with a novel antigen, tetanus toxoid. Blood samples were collected prior to and at 4-5-day intervals for 28 days after immunization. Plasma total immunoglobulins (IgG and IgM), complement levels (C3 and C4), tetanus antibody titers, and cortisol were assessed. Antibody levels were lowest in monkeys treated with antidepressants regardless of specific drug treatment or early rearing condition. Drug-treated subjects had elevated plasma immunoglobulins and complement protein levels. Cortisol was also highest in drug-treated subjects. These results should be considered when prescribing commonly used antidepressants for treatment of childhood disorders.

Adolescent↗

PubMed1998

Unexpected sarcolemmal complement membrane attack complex deposits on nonnecrotic muscle fibers in muscular dystrophies.

Antibody-dependent complement-mediated muscle fiber injury is a hypothetical immune effector response in inflammatory muscle diseases. Moreover, a sarcolemmal alteration in muscular dystrophies might trigger antibody-independent activation of the alternative complement pathway. We therefore searched for C5b9 complement membrane attack complex (MAC), immunoglobulin (Ig)G, and IgM deposits on nonnecrotic muscle fibers in muscle specimens from 81 patients with inflammatory myopathies, 45 patients with muscular dystrophies, and 19 patients with necrotizing myopathies. Sarcolemmal MAC deposits were present on nonnecrotic fibers (C+ fibers) in only two unusual types of inflammatory myopathy. By contrast, seven of 17 facioscapulohumeral dystrophy, four of nine limb-girdle dystrophy, and three of six merosin (laminin-alpha-2)-positive congenital muscular dystrophy but none of the Becker or Duchenne dystrophy specimens harbored C+ fibers. None of the C+ fibers immunostained for IgG or IgM, and none failed to immunostain for CD59 or CD46-inhibitors of the complement cascade. Our findings do not support a role for antibody-dependent complement-mediated muscle fiber injury in the major inflammatory muscle diseases. The cause and pathogenetic significance of the C+ fibers in the different types of muscular dystrophies remains to be elucidated.

Adolescent↗

PubMed1981

Isolation of three separate anaphylatoxins from complement-activated human serum.

Recent methodologies used in preparing anaphylatoxins from complement-activated serum are described. Activation of the alternative pathway generates C3a and C5a; however, activation of the classical pathway is required to generate the anaphylatoxin from C4. This article describes an activation scheme that simultaneously generates all three of the anaphylatoxins (e.g., C3a, C4a and C5a) in human serum and outlines a procedure for isolating each as homogeneous products. Purification of intact anaphylatoxins directly from complement-activated serum takes place only if an exopeptidase in serum, known as carboxypeptidase N (SCPN), is properly inhibited. A new series of mercapto derivatives of arginine analogs are introduced as potent and effective inhibitors of SCPN. These inhibitors permit normal complement activation but prevent degradation of the released activation fragments C3a, C4a or C5a. The SCPN inhibitor previously used was 6-aminohexanoic acid (EACA), but it required a 1 M concentration for effective inhibition, the substituted mercapto-guanido compounds prove to be effective in the mM range.

Aminocaproic Acid↗

PubMed1997

Resistance of ovarian teratocarcinoma cell spheroids to complement-mediated lysis.

We have shown previously that it is possible to target complement-mediated killing against cultured ovarian tumour cells in vitro. As malignant ovarian cells usually grow in solid nodules in vivo, we have in the present study examined the effectiveness of complement killing against ovarian teratocarcinoma cells (PA-1) growing in three-dimensional tumour microspheroids (TMSs). Our study shows that PA-1 cells growing in TMSs are less susceptible to complement-mediated killing than cells growing in monolayer cultures, even after neutralization of protectin (CD59), the main inhibitor of complement lysis. Cells in suspension and cells growing in TMSs showed a similar expression of membrane co-factor protein (MCP, CD46) and CD59. Decay-accelerating factor (DAF, CD55) was not detected on the surface of cells in suspension, but appeared focally on the outermost cell layers of the TMSs. Complement-activating antibodies bound to all PA-1 cells in suspension but only to the most peripherally located cells in TMSs, even though the target antigens were similarly expressed in the two systems. Antibody-induced complement activation on PA-1 cells in suspension led to C3 and C5b-9 deposition on most cells, while C3 and C5b-9 were only found on the outermost layers of the TMSs. The increased complement resistance of tumour cells growing in three-dimensional spheroids is partly because of an insufficient penetration of antibodies and complement into the TMSs. TMSs are a useful model for the development of more efficient ways to kill malignant cells in micrometastases with monoclonal antibodies and complement.

Antibodies, Monoclonal↗

PubMed1989

Platelet-activating factor enhances complement-dependent phagocytosis of diamide-treated erythrocytes by human monocytes through activation of protein kinase C and phosphorylation of complement receptor type one (CR1).

Oligomerization of band 3 protein has been recently indicated as an early event in senescent or damaged red cell membrane followed by specific deposition of anti-band 3 antibodies and binding of complement C3 fragments. The band 3-anti-band 3-C3b complex is recognized by homologous monocytes, and phagocytosis ensues. This study shows that recognition of the anti-band 3-C3b complex by the monocyte C3b receptor type one (CR1) plays a crucial role in the process of removal of damaged red cells. Indeed, blocking of monocyte CR1 with an anti-CR1 monoclonal antibody abrogated phagocytosis of diamide-treated red cells. Platelet-activating factor (PAF) is a phospholipid mediator involved in inflammatory processes. Nanomolar (R)-PAF enhanced the CR1-dependent phagocytosis of diamide-treated human red cell and of sheep red cells coated with C3b, induced the fast translocation of protein kinase C to monocyte membrane compartment, and stimulated the phosphorylation of monocyte CR1. The biologically inert lyso-PAF and the enantiomer (S)-PAF were inactive. PAF receptor antagonists and inhibitors of protein kinase C blocked the enhancement of phagocytosis induced by PAF. Protein kinase C translocation, phosphorylation of CR1, and stimulation of this receptor to an active state capable of mediating phagocytosis represent a novel pathway by which PAF interferes with red cell homeostasis and possibly modulates inflammatory reactions and host mechanisms against infections.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1986

Inhibition of complement dependent experimental inflammation in human skin by different heparin fractions.

The anticoagulant activity of heparin is dependent on its affinity for antithrombin III (AT III) and on its molecular weight. In contrast, heparin fractions differing in these respects are equally effective inhibitors of the human complement system in vitro. In this study we designed and evaluated a model to investigate the effects of different heparin fractions on a complement dependent inflammation. Locally administered heparin, in a dose-dependent manner, inhibited the flare, itch and wheal responses induced by intradermal injection of heat-aggregated human IgG (HAGG). These reactions were also inhibited by the antihistamine mepyramine, favouring the view that HAGG activates complement and that the observed inflammatory response is mediated by anaphylatoxin liberation of histamine. Similar cutaneous reactions induced by trypsin, which can generate C3a and C5a by proteolysis of C3 and C5, the histamine liberator compound 48/80 or histamine were inhibited by mepyramine but not by heparin. Thus it is strongly suggested that heparin inhibits the HAGG induced reactions by modulating the early pre-C3 steps of complement activation. On a weight basis heparin fractions differing in AT III-affinity or in average molecular weight (5,000 and 16,000 D) were equally potent modulators of the HAGG-induced inflammation. We conclude that heparin can inhibit an apparently complement-dependent inflammation irrespective of its AT III-affinity or of its size, and suggest that a heparin with low anticoagulant activity could be of value as a modulator of inflammation and should be useful in investigating the consequences of complement inhibition in inflammation.

Animals↗

PubMed2004

A novel RNA splice site mutation in the C1 inhibitor gene of a patient with type I hereditary angioedema.

We describe a patient with type I hereditary angioedema presenting recurrent episodes of skin swelling and abdominal pain. Laboratory examination showed reduced levels of CH50 and C4 with a normal C3 level. The C1 inhibitor was decreased to 7.0 mg/dl (normal, 10-25 mg/dl) with a remarkably reduced activity (<25%; normal, 80-125%). DNA analysis of the C1 inhibitor gene revealed a novel point mutation at the 3' acceptor mRNA splice site of the intron 5 (G-->A at nucleotide 8722). This mutation may abolish the correct splicing of the intron 5 and create unstable mRNA.

Angioedema↗

PubMed2001

Complement evasion by Borrelia burgdorferi: serum-resistant strains promote C3b inactivation.

The most characteristic features of the Lyme disease pathogens, the Borrelia burgdorferi sensu lato (s.l.) group, are their ability to invade tissues and to circumvent the immune defenses of the host for extended periods of time, despite elevated levels of borrelia-specific antibodies in serum and other body fluids. Our aim in the present study was to determine whether B. burgdorferi is able to interfere with complement (C) at the level of C3 by accelerating C3b inactivation and thus to inhibit the amplification of the C cascade. Strains belonging to different genospecies (Borrelia garinii, B. burgdorferi sensu stricto, and Borrelia afzelii) were compared for their sensitivities to normal human serum and abilities to promote factor I-mediated C3b degradation. B. burgdorferi sensu stricto and B. afzelii strains were found to be serum resistant. When the spirochetes were incubated with radiolabeled C3b, factor I-mediated degradation of C3b was observed in the presence of C-resistant B. afzelii (n = 3) and B. burgdorferi sensu stricto (n = 1) strains but not in the presence of C-sensitive B. garinii (n = 7) strains or control bacteria (Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis). Immunoblotting and radioligand binding analyses showed that the C-resistant strains had the capacity to acquire the C inhibitors factor H and factor H-like protein 1 (FHL-1) from growth medium and human serum. A novel surface protein with an apparent molecular mass of 35 kDa was found to preferentially bind to the N terminus region of factor H. Thus, the serum-resistant B. burgdorferi s.l. strains can circumvent C attack by binding the C inhibitors factor H and FHL-1 to their surfaces and promoting factor I-mediated C3b degradation.

Animals↗