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Results for “Complement Pathway, Alternative”

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PubMed1990

Aspergillus fumigatus complement inhibitor: production, characterization, and purification by hydrophobic interaction and thin-layer chromatography.

Aspergillus fumigatus has previously been shown to produce a soluble extracellular inhibitor of the alternative complement pathway, called Aspergillus complement inhibitor, or CI. We now report an efficient method for production of CI which relies on the fact that poorly conidiating cultures yielded CI activity with approximately sevenfold-higher potency than CI produced by conidiating cultures. CI from poorly conidiating cultures provided 50% inhibition of alternative pathway-mediated binding of 125I-labeled complement component C3 to cryptococcal blastoconidia at a mean concentration of 60 micrograms/ml. The ability of crude CI to inhibit the alternative complement pathway seemed to be independent of intact protein or polysaccharide structure, as evidenced by resistance of inhibitory activity to digestion by proteases, including subtilisin, alpha-chymotrypsin, papain, and pepsin as well as endoglycosidases F and H. Separation of the active inhibitory component of CI from contaminating materials contained in crude CI preparations was achieved by using Phenylsuperose hydrophobic interaction chromatography in a fast protein liquid chromatography system. The active material proved to be extremely hydrophobic, desorbing from the column only during elution with ethanol; it contained only 15% protein and 5% polysaccharide. Furthermore, results from preparative thin-layer chromatography indicated that lipids which comigrated with phosphatidylserine/phosphatidylinositol and phosphatidylethanolamine possessed significant complement-inhibitory activity. Taken together, these data suggested that phospholipids from A. fumigatus contributed to the functional activity of CI.

Aspergillus fumigatus↗

PubMed1983

Activation of the alternative pathway of complement by monosodium urate monohydrate crystals and other inflammatory particles.

Activation of serum C3 by monosodium urate monohydrate (MSU) crystals and other particles was determined by immunofixation following electrophoretic separation of C3 and its activation products. Densitometry allowed quantitation of results. MSU, hydroxyapatite, brushite, and calcium pyrophosphate dihydrate crystals split C3 under conditions which demonstrate activation via the alternative pathway (AP). Quantitatively similar results were obtained in immunoglobulin deficient serum. Activation was crystal specific and was reduced by heating, grinding, sonication, and aging of crystals. Other inflammatory particles (e.g., blackthorn) activated C3 via the AP: noninflammatory particles (e.g., diamond) caused insignificant activation. It is suggested that particle-induced activation of the alternative pathway of complement may be important in the initiation of crystal-induced synovitis.

Agammaglobulinemia↗

PubMed1986

Activation of the alternative pathway of complement by an antitumor (1----3)-beta-D-glucan from Alcaligenes faecalis var. myxogenes IFO 13140, and its lower molecular weight and carboxymethylated derivatives.

An antitumor (1----3)-beta-D-glucan with a number-average degree of polymerization (DP) of 540 from Alcaligenes faecalis var. myxogenes IFO 13140, and its lower molecular weight derivatives were found to activate the alternative pathway of complement (APC), as judged by hemolytic and immunoelectrophoretic analyses. Of the native and derivative (1----3)-beta-D-glucans measured, the smallest one that showed APC-activating ability was that with a DP of about 20. The effect of carboxymethylation of the (1----3)-beta-D-glucans with DPs of 49, 131 and 540 on their APC-activating ability was investigated. In any (1----3)-beta-D-glucan the ability was decreased with the increase of carboxymethyl substitution and was completely lost when about one carboxymethyl group per glucose residue was incorporated. In contrast, strong inhibitory ability against C1 hemolytic activity appeared on carboxymethylation.

Alcaligenes↗

PubMed1978

Activation of the alternative pathway of complement by Entamoeba histolytica.

A cytopathogenic effect was observed when Entamoeba histolytica was exposed to human sera from individuals with no clinical history or laboratory evidence of amoebiasis. Absorption studies showed that the effect was not due to natural antibodies. Studies performed using ethylenediamine tetracetic acid (EDTA), cobra venom factor (CoF) and heat-inactivation at 56 degrees C, indicated that the cytopathogenic effect was complement dependent. Furthermore, by using ethylene glycol tetracetic acid (EGTA) and Mg++, zymosan, heat-inactivation at 50 degrees C to destroy the activity of factor B of the alternative pathway, as well as electrophoretic studies with anti-human factor B, it was possible to determine that E. histolytica activated the properdin pathway. Finally, complement determinations indicated that incubation of E. histolytica with normal human serum consumed complement. The diminution in CH50 correlated with a consumption of C3 but not of C1, C4 and C2. It was concluded from these results that trophozoites of E. histolytica activate the alternative pathway of the human complement system.

Animals↗

PubMed1990

[Quantitation of intact form of complement protein B and its fragment Ba in human serum by radioimmunoassay].

A sensitive solid-phase radioimmunoassay for intact complement protein B and its smaller fragment Ba is described which quantitates human B and Ba to 30 ng/ml. The assay was proved to be useful to evaluate the activation of the alternative pathway of the complement system by measuring intact B and Ba in normal human sera activated with zymosan. In sera from patients with systemic lupus erythematosus (SLE), the level of intact B was decreased and that of Ba was increased in the active phase, and the level of Ba was increased though intact B which was within normal limits in the inactive phase. The present result suggests that the activation of the alternative pathway is occurring both in the active and inactive phase in SLE, and the measurement of intact B and Ba concentration in pathological sera would be useful to evaluate the activation of the alternative complement pathway.

Adult↗

PubMed1992

Activation of the alternative pathway of complement is an important component of hyperacute rejection of rabbit hearts by human blood.

Hyperacute discordant xenograft rejection can be simulated by blood perfused working isolated heart. The survival of the heart is dependent on its functional integrity, and the preparation is thus sensitive to early myocardial damage. Perfusion of rabbit hearts with human blood results in immediate graft destruction by a thrombotic process. Prevention of this process results in rapid rejection at about 20 min by the alternative pathway of complement.

ABO Blood-Group System↗

PubMed1986

Purification and characterization of complement activating-acidic polysaccharide from the root of Lithospermum euchromum Royle.

An extraordinary potent anti-complementary substance was isolated from the root of Lithospermum euchromum Royle (Japanese name: Nan-shikon) which activates the complement system in vitro, and the active principle was shown to be acidic polysaccharide (LR-polysaccharide IIa). LR-polysaccharide IIa was purified by chromatographies on DEAE-Sepharose, Sephadex G-100, concanavalin A-Sepharose, Ricinus communis agglutinin conjugated Sepharose, Sepharose CL-6B and Sepharose CL-2B. LR-polysaccharide IIa was found to be composed of rhamnose, fucose, arabinose, xylose, mannose, galactose and glucose in the molar ratios of 2.0:2.5:3.4:2.8:5.6:9.6:14.4. The polysaccharide also contained 15% of galacturonic acid and 3.8% of protein. The methylation analysis of the polysaccharide showed that rhamnose, arabinofuranose, xylose, glucose and galactose are present as a part of the nonreducing terminal residues. The main chain and side chains are composed of ----3Glc1----,----3Gal1----,----6Man1----,----4Gal1, [corrected] and the branching points consist of (formula; see erratum) These results indicated that LR-polysaccharide IIa has a highly complicated structure. A marked consumption of C4 was observed after the incubation of the serum with LR-polysaccharide IIa in the presence of the Ca++ ion. The anti-complementary activity of LR-polysaccharide IIa was reduced partially in the absence of the Ca++ ion. After the incubation of the serum with LR-polysaccharide IIa in the absence of Ca++ ion, a cleavage of C3 in the serum was found to have occurred through immunoelectrophoresis as well as from the consumption of the complement when rabbit erythrocytes were used in the assay system. These results indicate that the mode of complement activation by LR-polysaccharide IIa is via both the alternative and classical pathways. Complement titer also decreased in guinea pigs upon i.p. injection of LR-polysaccharide IIa.

Animals↗

PubMed1979

In vitro fixation of guinea pig complement by renal biopsies.

The in vitro fixation of heterologous complement by cryostat sections of human renal biopsy material was studied to determine the mechanism of complement activation. Various types of guinea pig sera with different parts of the complement system inhibited were used, the fixation of complement being detected by direct immunofluorescence. Cases of idiopathic focal nephritis with mesangial IgA (mesangial IgA disease), Henoch-Schönlein purpura (HSP) and mesangio-capillary glomerulonephritis (MCGN) fixed complement by the alternative pathway alone and in systemic lupus erythematosus (SLE) both the classical and alternative pathways were involved. Only one of the seven cases of membranous glomerulonephritis fixed complement and this was by the classical pathway. After prior treatment with C3b inactivator, the in vitro complement fixation in mesangial IgA disease, HSP and MCGN was greatly reduced. In SLE it was slightly reduced and in membranous glomerulonephritis there was no change. This is a convenient method of studying the biological properties of complexes which is believed to reflect the in vivo behaviour of the tissue deposited complex.

Animals↗

PubMed1981

Defective activation of the alternative pathway of complement in two brothers with ataxia-telangiectasia.

Two brothers with ataxia-telangiectasia and recurrent respiratory tract infections are presented. Immunological investigations showed normal immunoglobulin levels (except for the absence of IgA in one child) with absence of haemagglutination inhibiting antibody response to inactivated influenza virus vaccine, normal total lymphocyte counts with decreased T cell numbers, absence of delayed hypersensitivity skin reaction to PPD, in vitro unresponsiveness of T lymphocytes to PHA with presence of a serum inhibitor able to depress normal lymphocyte transformation, and normal phagocytosis and killing of Staph. aureus by peripheral blood polymorphonuclear leucocytes. Complete complement screening revealed a non-functioning alternative pathway in both brothers. The presence of normal factor B lytic activity after isoelectrofocusing the serum and inhibition of the lytic activity of purified components with the patients' serum raised the possibility of a serum inhibitor. The nature of this was not elucidated but it may be one of the reasons why patients with ataxia-telangiectasia have an increased incidence of infections.

Ataxia Telangiectasia↗

PubMed1983

Activation of the alternative pathway of complement by Acanthamoeba culbertsoni.

Normal human serum (NHS) contained an amoebicidal property for Acanthamoeba culbertsoni. Killing was quantitated by measuring the ability of the amoebae to undergo cell division subsequent to exposure to NHS, and also by microscopical examination. Plasma membrane disruption and extrusion of intracellular components occurred within 5-10 min following exposure to NHS. Adsorption of specific antibody did not remove the amoebicidal activity while heating serum at 56 degrees C/30 min or treatment with zymosan prevented the killing of A. culbertsoni. Haemolytic complement was consumed and C3 conversion occurred during the incubation of NHS with amoebae. Killing required the presence of the late complement components. The findings that (a) amoebae were killed in C2 deficient human serum and ethylene glycol tetra-acetic acid (EGTA), but not ethylenediamine tetra-acetic acid (EDTA) treated NHS; (b) haemolytic complement consumption, which occurred by incubating NHS with the amoebae, could be prevented by addition of EDTA, but not EGTA and (c) conversion of C3 occurred in the presence of EGTA, but not EDTA, indicated that activation of the alternative pathway of complement was involved. This may be of importance as a natural defence mechanism in humans against A. culbertsoni infections.

Amoeba↗

PubMed1989

Analysis of recognition in the alternative pathway of complement. Effect of polysaccharide size.

Covalent attachment of the complement (C) protein C3b to polysaccharides on biologic particles which activate the alternative pathway leads to changes in the affinity of C3b for factor H, a regulatory protein of the C system. In this study the size of the site with which the polysaccharides interact and its special relationship to the thioester site were investigated using a fluorimetric assay and soluble C3b attached to low m.w. polysaccharides. Oligomers of alpha 1-6 and alpha 1-4 polyglucose and beta 1-2 polyfructose were prepared and attached to C3b at the thioester site. C3b bound to monomeric, dimeric, or trimeric sugars exhibited the same interaction with factor H as free C3b, i.e., there was no effect due to attachment alone. Beginning with tetrameric oligosaccharides a linear decrease in factor H binding was observed with increasing oligosaccharide size and the effect reached an apparent maximum with large polysaccharides. Maximum inhibition of factor H function was estimated to occur at a length of 16 saccharide units. The results suggest that this site, which regulates the inactivation rate of surface-bound C3b and thus the activation of the alternative pathway of C, spans a maximum of 13 sugar units (less than 65 A) starting four units (approximately 15 A) from the thioester site in C3b.

Binding Sites↗

PubMed1993

Differences in the activity of the alternative pathway of complement in BALB/c and C57Bl/6 mice.

The deposition of C3b on the surface of zymosan was assessed in inbred strains of mice. Mg(2+)-EGTA plasma from C57Bl/6 and BALB/c mice was incubated with zymosan and deposited C3b was eluted by methylamine. Eluted C3b was detected and quantified by Western blot and an enzyme-linked immunosorbent assay. 3- to 4-fold more C3b was deposited on zymosan incubated with C57Bl/6 plasma than on zymosan incubated with BALB/c plasma (p < 0.01). Data on the kinetics of deposition of C3b suggest a faster and greater activity of the alternative pathway of complement (ACP) in C57Bl/6 than in BALB/c. Higher C3b deposition in C57Bl/6 plasma occurs in the presence of higher plasma factor H concentration (1.3-fold of BALB/c concentration; p < 0.01) and is accompanied by higher factor H deposition on zymosan (3- to 10-fold of BALB/c concentration; p < 0.01). Demonstrable differences in the activity of the proteins of the ACP may provide a biological basis for the genetic variation in innate resistance to infectious organisms observed in inbred strains of mice.

Animals↗

PubMed1987

Primary cultures of murine astrocytes produce C3 and factor B, two components of the alternative pathway of complement activation.

We have investigated the production of C3, C4, and factor B complement components in primary cultures of murine astrocytes and in clonal cell lines belonging to the astrocytic lineage by immunoprecipitation of secreted labeled polypeptides. Although C4 has not been detected, C3 appeared to be constitutively synthesized both by two transformed astroblastic cell lines and by astrocytes in primary cultures. In contrast, factor B was only secreted upon lipopolysaccharide stimulation both in astroglial primary cultures and in an immortalized astrocytic cell line. The eventual physiologic relevance of an endogenous brain production of components of the alternative pathway of complement activation is discussed.

Animals↗

PubMed1984

Mediation of the killing of rough, mucoid isolates of Pseudomonas aeruginosa from patients with cystic fibrosis by the alternative pathway of complement.

The mechanism of killing of 12 serum-sensitive strains of mucoid Pseudomonas aeruginosa isolated from patients with cystic fibrosis was investigated. A quantitative assay indicated that more than 90% of cells were killed in 50% normal human serum (NHS). All strains failed to grow in NHS concentrations of greater than 10%. Killing was unaffected by adsorption of NHS with the mucoid bacteria or chelation with MgCl2-ethyleneglycol bis(beta-aminoethyl ether)N,N1-tetraacetate (MgCl2-EGTA) but was abolished in serum heated to 50 C for 20 min. Incubation of NHS with mucoid P. aeruginosa reduced the hemolytic capability of MgCl2-EGTA-chelated NHS against rabbit red blood cells by 56%-99%. Killing of the serum-sensitive mucoid strains was also seen in hypogammaglobulinemic serum. These data suggest that killing of such strains by NHS can occur via antibody-independent activation of the alternative pathway of complement. The importance of this finding lies in the implication that complement levels in the lungs of patients with cystic fibrosis who are colonized by these organisms are inadequate to deal with this chronic, progressive infection.

Adult↗

PubMed1987

Evidence for activation of complement in patients with AIDS related complex (ARC) and/or lymphoadenopathy syndrome (LAS).

The complement system was examined in 16 patients with AIDS-related complex (ARC) (n = 5) and/or lymphoadenopathy syndrome (LAS) (n = 11). Of these patients 62.5% showed an impairment of classical and/or alternative pathway activity associated with the presence of cleavage fragments of C3 and/or B and a significant reduction of many complement factors. The data indicate pathological complement activation in these patients through the classical and/or alternative pathway. Complement activation was more severe in patients with ARC than in those with LAS, and greater in drug abusers than homosexuals. The lack of efficient complement in the patients can be considered an 'acquired complement deficiency' with possible importance in the failure to combat the HIV attack.

AIDS-Related Complex↗

PubMed1979

The septic burned patient: a model for studying the role of complement and immunoglobulins in opsonization of opportunist micro-organisms.

Studies were performed to determine the effects of septicemia on complement levels and activities and opsonic function in septic and nonseptic burned patients. None of the nonseptic burned patients had consumption of classical pathway activity during their clinical course. Patients who did not survive septicemia had consumption of all of the classical complement components (C1-C5) prior to and during their septic episodes. Patients who survived septicemia had multiple patterns of classical complement pathway consumption. In these patients, classical pathway activity was restored to normal following the last positive blood culture. Alternative complement pathway consumption was demonstrated in only one of the septic burned patients, as evidenced by decreased factor B and C3b INA levels and decreased C3 and C5 conversion in sera treated with 10 mM ethylene glycol tetraacetic acid and 10 mM MgCl(2) (MgEGTA) and in untreated sera. In all of the other septic patients and in the nonseptic patients, reduction in C3 and C5 conversion in MgEGTA sera and untreated sera was not associated with decrease in factor B or C3b INA. Reduction in complement levels and activities did not reduce the ability of the patients' sera to promote phagocytosis and intracellular killing of their infecting micro-organisms by normal human peripheral polymorphonuclear leukocytes. The results indicate that measurement of classical pathway activity in burned patients can be used as a diagnostic tool for predicting the severity of septic episodes and for monitoring recovery. In addition, the observation that complement consumption did not reduce the opsonic capacity of the patients' sera for their infecting micro-organisms suggests that current concepts regarding the role of immunoglobulins and complement in opsonization of opportunist micro-organisms require re-evaluation.

Adolescent↗

PubMed1989

Inhibitory activity of Jatropha multifida latex on classical complement pathway activity in human serum mediated by a calcium-binding proanthocyanidin.

This study isolates and characterizes the anti-complement constituent(s) present in the latex of Jatropha multifida, in an attempt to explain the traditional application of the latex in the treatment of infected wounds. Guided by the inhibition of classical pathway (CP) complement activity in human serum, a polymer was isolated which could be characterized as a proanthocyanidin. The polymer inhibits CP activation of the complement cascade, while alternative pathway (AP) activation is relatively insensitive to the polymer. This is due to the selective depletion of Ca2+, but not Mg2+, from the incubation medium.

Anthocyanins↗

PubMed1985

Activation of the alternative pathway of complement by skin immune deposits.

Skin immune deposits at the basement membrane zone have been demonstrated by functional assays to activate complement. This important biologic function has not yet been explored for immune deposits present in other locations mainly because many cytoplasmic structures in the skin have the capacity to activate the complement cascade by the classical pathway. In this study the capacity of immune deposits to activate directly the alternative pathway was examined using a functional guinea pig C3 binding test. This test was devised so as to avoid complement activation by normal cutaneous structures, thus it did not examine the capacity of immune reactants to activate the classical pathway. The main findings were that alternative pathway activation could be demonstrated only when human C3 deposits were seen by direct immunofluorescence, but not all C3 deposits were found to activate the alternative pathway; such activation was restricted to vascular deposits; the phlogistic potential of the immune deposits correlated with serologic evidence of ongoing immune reactions, i.e., hypocomplementemia and circulating immune complexes. It is suggested that this test provides data on one aspect of the phlogistic potential of skin immune deposits not detectable by direct immunofluorescence.

Animals↗