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PubMed1978

'In vitro' study of a reaction between the complement system and cellular DNA.

A direct reaction between the complement system and DNA in nuclei was demonstrated in vitro by an indirect immunofluorescence technique using cryostat-cut sections of rat liver as a substrate. This reaction occurred at physiological conditions of pH and molarity and was abolished by pre-treatment of the tissue sections by DNase. It begins by the fixation of C1q and involves the fixation and probably the activation of apparently all the components of the classical pathway of the complement system. The pattern of fluorescence given by this reaction was similar to the pattern given by anti-DNA antibodies present in sera from systemic lupus erythematosus (SLE) patients.

Animals↗
PubMed1985

Ganglioside modulation of lipopolysaccharide-initiated complement activation.

Highly purified preparations of mouse gangliosides have been demonstrated to bind to purified preparations of lipopolysaccharide (LPS). In some instances, the binding has been demonstrated to be dependent upon the presence of sialic acid in the ganglioside preparation. The binding of gangliosides to LPS from the deep rough Salmonella minnesota Re mutant has suggested that the interaction involves the lipid A-2-keto-3-deoxyoctulosanate region of the LPS macromolecule. The interaction between gangliosides and LPS has been demonstrated to result in an abrogation of lipid A dependent activation of the classical pathway of serum complement by Re LPS. Surprisingly, however, the presence of sialic acid containing glycolipids has been shown to enhance significantly the capacity of LPS to initiate activation of the alternative pathway of complement. These data suggest that sialic acid can enhance as well as inhibit the formation of a stable alternative-pathway C3 convertase.

Animals↗
PubMed1987

Activation of human serum complement by bacterial lipopolysaccharides: structural requirements for antibody independent activation of the classical and alternative pathways.

A variety of bacterial lipopolysaccharide (LPS) preparations with highly defined primary polysaccharide chemical structure and/or aggregate macromolecular composition have been employed to examine the molecular requirements for activation of the classical and alternative pathways of human serum complement. Evidence is presented for two independent modes of polysaccharide dependent activation of the APC by LPS. One mechanism is dependent upon specific O-antigen polysaccharides and the second is defined by a specific L-glycero-D-mannoheptose/glucose region of the core oligosaccharide. LPS O-antigen polysaccharide but not core oligosaccharide determinants can convert sheep erythrocytes to cells capable of initiating the APC. The data presented provide convincing evidence that the tertiary assembly of individual LPS subunits into an aggregate macromolecule is a critical determinant in the expression of APC activity by LPS. The results of these studies provide strong evidence that CPC activation by LPS is restricted to the Re-chemotype and isolated lipid A. LPS isolated from other R-chemotypes as well as native wild type LPS preparations do not activate the CPC, in spite of the fact that the former LPS preparations contain more lipid A than polysaccharide on a percentage by wt basis. The presence of core polysaccharide L-glycero-D-mannoheptose, which provides a critical recognition role for activation of the APC, appears to negatively regulate CPC activation in a similar inverse relationship. In addition, the presence of polysaccharide containing LPS subunits in synthetic mixed LPS micellar aggregates can also restrict CPC activation by Re LPS subunits, most probably by steric hindrance at the LPS macromolecular surface. Our data are consistent with the hypothesis that activation of either pathway of human serum complement by a given LPS preparation is a mutually exclusive event dictated by the presence or absence of L-glycero-D-mannoheptose.

Complement Activation↗
PubMed1989

[Major complement inhibiting factors from the venom of the Central Asian cobra Naja naja oxiana].

The properties of two anticomplementic factors isolated by CM-Sepharose chromatography from the basic non-adsorbed on DEAE-Sepharose fraction of the Central Asian cobra Naja naja oxiana venom, were studied. Of these three factors (CFB-I, CFB-II and CFB-III) the latter had been characterized earlier. CFB-I was shown to be a protein with an N-terminal Asp and a molecular mass of about 39 kDa (data from gel chromatography); its content in the venom is 3.6 mg/g of dry venom. The protein inhibits mainly the classical pathway of the complement activation, being bound to component C4 (Ki = 9 nM). CFB-I seems to be analogous to the CI inhibitor from the venom of the Naja haje cobra. An analysis of the N-terminal sequence of CFB-II showed it to be identical to the earlier characterized cytotoxin I. CFB-I inhibits the formation of C3 convertase with Ki = 2.2-2.8 microM by way of binding to C4b and thus interfering with the component C2 sorption.

Animals↗
PubMed1987

[Formation of classical C3 convertase during the alternative pathway of human complement activation].

The fluid phase C3 convertase of the alternative pathway of human complement activation has been constructed from the isolated C3 component and from purified factors B and D. The enzyme was able to activate the isolated components C4 and C2 in the presence of C4 but had no effect on C2 in the absence of C4. The C4 and C2 activation was monitored by the loss of their hemolytic activity during the incubation with the alternative fluid phase C3 convertase. The activation of C4 and C2 components by the membrane-bound alternative C3 convertase formed on red cells (EC3bBb) was followed by the formation of C3 convertase of the classic pathway--EC4b2a. This resulted in the enhancement of hemolysis.

Animals↗
PubMed1984

[Binding and activation of the first component of human complement on artificial matrices].

Artificial sorbents that comprise macroporous glass covered by the copolymer of N-vinylpyrrolidone and N-substituted acrylamide have been synthesized. Aminoethanol is bound to acrylic acid residue in one sorbent (AE-glass), whereas the other sorbent involves immunoglobulin G with the hexamethylenediamine spacer (IgG-glass). C1q binds specifically to IgG-glass with Ka 4,07(+/- 0,32) X 10(7) M-1. Free energy of the C1q binding to IgG-glass is twice higher than that of its binding to monomeric IgG. This evidences that one C1q molecule associates with two IgG molecules of the sorbent. A weak nonspecific sorption of C1q to AE-glass was found. Both specific (on IgG-glass) and nonspecific (on AE-glass) sorption of the first component of complement activate the classical pathway in human serum as manifested in the consumption of the C4, C2, C3 and C5 components. IgG-glass was employed for C1q isolation from human serum by affinity chromatography, whereas unbound part of serum may be used as a reagent R1q. The yield of highly purified C1q after IgG-glass affinity chromatography and gel filtration on Sephacryl S-300 is 63,6%.

Chemical Phenomena↗
PubMed1994

Immune complexes and nephropathies associated with Plasmodium inui infection in the rhesus monkey.

The pathogenesis of renal diseases associated with Plasmodium malariae infections is still not fully understood. The present work is concerned with the infection caused by P. inui in the rhesus monkey Macaca mulatta as a potential model for human quartan malaria, which the monkey parasite resembles in morphology and schizogonic behavior. Various aspects of the disease were studied. Changes in the levels of serum complement components C3 and C4 indicate activation of complement through the classical pathway. A few days after infection, IgG antibody titers increased, coinciding with low levels of parasitemia, which suggests that some of these antibodies are protective. Immunofluorescence testing of kidney tissue showed a predominance of IgM antibodies over IgG, C3, C4, albumin, and fibrinogen, which was detected in a number of the infected monkeys. These findings were consistent with those seen in humans with P. malariae infection and indicate that the P. inui/rhesus monkey model is likely to be appropriate for the study of different aspects of quartan malaria.

Albumins↗
PubMed1993

Interaction of C1 with HIV-1.

In contrast to animal retroviruses such as murine leukemia virus, HIV-1 is not lysed by human complement. Nevertheless, HIV-1 activates complement via the classical pathway independently of antibody. Evidence is provided for activation of the reconstituted C1 complex by the virus, resulting from direct interaction between C1q and the external part of the viral transmembrane envelope protein (sgp41). Using C1q fragments and synthetic peptides covering the putative interaction regions in C1q and sgp41, we obtain evidence that the C1q/HIV-1 interaction involves: A site on C1q that appears to be located in the intermediary region between the collagen-like and the globular regions of C1q, and which may be conformational, involving two or more C1q chains. A site on gp41 located between residues 601 and 613 (gp160 nomenclature), i.e. within the immunodominant domain of HIV-1. This site shares homology with the corresponding region of HIV-2.

Amino Acid Sequence↗
PubMed1991

Direct binding of complement component C1q to human immunodeficiency virus (HIV) and human T lymphotrophic virus-I (HTLV-I) coinfected cells.

Previous studies have shown that coinfection of the human T lymphotrophic virus type I (HTLV-I) chronically infected cell line MT4 with human immunodeficiency virus type 1 (HIV-1) results in cells which spontaneously activate complement via the classical pathway. This complement activation was antibody independent, yet required C2, suggesting either direct C1, C4, or C2 activation. Because some animal retroviruses have been shown to bind human C1q directly, the present study investigated the possible direct binding of C1q by HIV coinfected MT4 cells. Coinfected cells bound both C1q present in serum and highly purified C1q. Binding of C1q resulted in formation of active C1 on the cell surface, which could in turn activate complement as shown by C4 consumption. The C1q binding was not HIV-isolate specific since infection of MT4 cells with any of three diverse isolates all induced C1q binding. Purified collagen-like region (CLR) and globular region (GR) fragments of C1q both bound to coinfected cells, suggesting a mechanism of binding by C1q similar to that of fibronectin-C1q binding. However, culture of coinfected cells in serum-free (fibronectin-free) medium did not reduce C1q binding. A second HTLV-I chronically infected line, SLB-1, also displayed increased binding of C1q after HIV infection. The H9 cell line, which is not HTLV-I infected, did not bind C1q after HIV infection. These results suggest that a retrovirus protein expressed by coinfected cells directly binds C1q resulting in classical complement activation. This type of activation may have profound biological effects in persons coinfected with HIV-1 and HTLV-I.

Cell Line↗
PubMed2000

Secretory IgA and complement levels in patients with hookworm infection in Zaria.

As a continuing investigation into the immunological reactions involved in hookworm infection the levels of secretory IgA (sIgA). IgM, IgA, complement C3 and C4 were studied in 57 Nigerians with hookworm infection and compared with those of 28 healthy, normal controls. The hookworm patients were divided into three groups based on the degree of anaemia (Hb1-7 and hypochromia +++). Group II had moderate anaemia (Hb8-11, hypochromia ++ and Group III had no signs of anaemia despite the underlying hookworm infection. The patients also comprised those in whom hookworm was the sole infection and those with hookworm associated with other parasites. Significant differences in the results between each patient subgroup and the controls were analysed using the student t-test. IgA was significantly elevated in patients with anaemia of mild to moderate severity and in patients with hookworm only (P < 0.05) while sIgA was significantly elevated in all subgroups compared to controls (P < 0.05). IgM was significantly elevated in-patients with marked anaemia, in-patients without anaemia and in those with hookworm infection associated with other parasites (P < 0.05). The difference in IgG levels between patients and controls was not significant (P 0.1). C4 was significantly elevated in patients with marked moderate anaemia and those with hookworm only (P < 0.05) while C3 levels were not significantly different in the subgroups compared with controls. These results suggest the possibility of polyclonal B-cell activation by T-independent antigens such as the polysaccharide cuticular antigens of the hookworms and the stimulation of the classical pathway of the complement system.

Adolescent↗
PubMed2005

Flavonoids from the leaves of Litsea japonica and their anti-complement activity.

Four flavonoids, epicatechin (1), afzelin (2), quercitrin (3), and tiliroside (4), were isolated from the leaves of Litsea japonica (Thunb.) Jussieu (Lauraceae). The structures of compounds were identified by comparing their chemical and spectral data with those previously reported. The flavonoids (1-4) were tested for their anti-complement activity against classical pathway of complement system. Compounds 2-4 showed inhibitory activity against complement system with IC50 values of 258, 440, and 101 microm, respectively, whereas 1 was inactive. For the evaluation of the structure-activity relationship of 5,7-dihydroxyflavones, myricitrin (5) from Juglans mandshurica also tested for it's anti-complement activity and is inactive in this assay system. Furthermore, compounds 2, 3, and 5 were hydrolyzed with naringinase to give kaempferol (2a), quercetin (3a), and myricetin (5a), and these were also tested for their activity. Of the three aglycones, 2a exhibited anti-complement activity with an IC50 value of 730 microM, while 3a and 5a were inactive. The inhibitory potencies of 2, 2a, 3, 3a, 5, and 5a against complement activity increased in inverse proportion to number of free hydroxyls on B-ring of 5,7-dihydroxyflavone. Of the compounds tested, 4 showed the most potent inhibitory activity against the complement system.

Complement Inactivator Proteins↗
PubMed2006

Anticomplement activity of cycloartane glycosides from the rhizome of Cimicifuga foetida.

A tetranor-cycloartane glycoside and two 9,19-cycloartane glycosides were isolated from the EtOAc-soluble fraction of the rhizome of Cimicifuga foetida. The structures of the compounds were determined to be cimilactone A (1), 25-O-acetylcimigenol 3-O-beta-d-xylopyranoside (2) and cimigenol 3-O-alpha-l-arabinopyranoside (3), respectively, using spectroscopic analysis. The three compounds were examined for their anticomplement activity against the classical pathway of the complement system. Compound 1 showed significant anticomplement activity with an IC(50) value of 28.6 microm, whereas compounds 2 and 3 were inactive.

Animals↗
PubMed2006

Adjuvant and immunostimulatory effects of beta-glucan administration in combination with lipopolysaccharide enhances survival and some immune parameters in carp challenged with Aeromonas hydrophila.

Combined effects of beta-glucan and lipopolysaccharide (LPS) on survival and immune response were studied in Cyprinus carpio that were challenged with the pathogen Aeromonas hydrophila. beta-Glucan from Saccharomyces cervisiae and LPS from a virulent strain of A. hydrophila were used in this study. Different concentrations of beta-glucan+LPS mixture were administered on days 1, 7, and 14 through different routes (intraperitoneal injection, bathing, and oral administration). Control and test fish were challenged by intraperitoneal injection of LD50 concentration of A. hydrophila on day 16 and subsequently, mortality and relative percent survival (RPS) were recorded. Intraperitoneal injection elicited 100% RPS even at the lowest concentration (100 microg beta-glucan+10 microg LPS); whereas, oral administration improved RPS rate of carps at higher concentration (1% beta-glucan+0.25% LPS). Bathing did not improve the RPS. Test animals injected with even the minimum dose of the immunomodulators (100 microg beta-glucan+10 microg LPS/fish) had a significant increase in total blood leukocyte counts and an increase in the proportion of neutrophils and monocytes. Superoxide anion production by macrophages was also elevated, which presumably aided the efficient killing of bacterial pathogen. Lower concentration of beta-glucan+LPS had an adjuvant effect on antibody production as pretreatment by injection of 100 microg beta-glucan+10 microg LPS/fish resulted in higher antibody titer against A. hydrophila following vaccination. RT-PCR analyses showed that the expression of interleukin-1beta mRNA did not increase in test fish when compared with the control. Classical and alternative complement pathways were not affected by either the dose or the route of administration of the compounds. It may be concluded that intraperitoneal injection and oral administration, and not the bathing, of beta-glucan+LPS mixture in carp could enhance resistance to challenge by A. hydrophila through changes in several non-specific and specific immune responses.

Adjuvants, Immunologic↗
PubMed2000

Immunomodulatory and anti-inflammatory activity of Picrorhiza scrophulariiflora.

Extracts of the rhizomes of Picrorhiza scrophulariiflora Pennell (Scrophulariaceae) were investigated for their in vitro and in vivo immunomodulatory properties. Diethyl ether extracts showed potent inhibitory activity towards the classical pathway of the complement system, the respiratory burst of activated polymorphonuclear leukocytes, and mitogen-induced proliferation of T-lymphocytes. Furthermore, such extracts showed anti-inflammatory activity towards carrageenan-induced paw edema. No effects were observed in experimentally induced arthritis in mice.

Adjuvants, Immunologic↗