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PubMedDate not supplied

Immunomodulatory activity of three Sri-Lankan medicinal plants used in hepatic disorders.

The effects of aqueous extracts of Osbeckia octandra whole plant, Melothria maderaspatana whole plant and Phyllanthus debelis leaves on the human immune system were investigated. The extracts showed strong anticomplement effects on both the classical and alternate pathways of the human complement system in vitro. The effects were dose-dependent and most pronounced in the classical complement pathway assay. The extracts also exhibited a direct dose-dependent inhibition of luminol-induced chemiluminescence of human polymorphonuclear leukocytes upon stimulation with zymosan.

Adjuvants, Immunologic↗
PubMedDate not supplied

Complement pathway activity in serum from patients with classical dengue fever.

Complement activity in 125 cases of classical dengue fever was examined through the measurement of haemolytic activity. During the first 3 d of fever, the classical complement pathway activity (CCPA) was not altered in 109 cases. After 4 d of fever, 9 of 16 patients in the viraemic period had CCPA decreased by 45% (995 +/- 119 units/ml) and serum complement component C4 decreased by 40% (10.4 +/- 0.9 mg/dl). The alternative complement pathway activity was not affected in any case tested throughout both viraemic and convalescent stages. Both CCPA and C4 persistently decreased in 3 of these 9 patients at the convalescent stage. A decrease in serum C3 was also observed in these 3 patients only, and circulating immune complexes (CIC) levels were particularly high in these 3 patients. These results indicate that there is little evidence of complement activation on days 1-3 of viraemia but that complement activation may occur subsequently. It is concluded that both CIC and other unknown factors not related to CIC may contribute to complement activation in some cases (9/125) of classical dengue fever.

Adult↗
PubMed1979

Classical and alternate complement pathway activities in paired dairy cow--newborn calf sera.

Hemolytic assays were used to compare alternate and classical C pathway activities in sera obtained from clinically normal newborn dairy calves and their mothers at the time of delivery. Mean alternate and classical CH50 concentrations in sera from newborn calves were both significantly lower than in their dams (P less than 0.001). The titer of alternate C pathway activity, expressed as CH50 units/ml, in sera from 17 calves was 12.9 +/- 5.5, whereas for the cows it was 25.8 +/- 6.2. The ratio of cow: calf serum alternate CH50 titers averaged 2.25 +/- 0.80 and ranged from 0.88 to 4.14. Classical CH50 titers were 78.0 +/- 42.7 units/ml in calf sera and 246.0 +/- 44.5 in cow sera. The ratio of cow: calf serum classical CH50 titers averaged 3.71 +/- 1.49 and ranged from 1.19 to 6.87. The wide range of values, noted for both the alternate and classical C pathways, within maternal and neonatal groups was assumed to reflect the biologic variability of complement levels in bovine serum. The possible relationships between deficient levels of alternate and classical CH50 activity in newborn calves and their susceptibility to infections is discussed.

Animals↗
PubMed1978

Possible mechanisms of the first step of the classical complement activation pathway: binding and activation of C1.

Different immunoglobulin preparations of human monoclonal IgM, normal human and rat IgG, as well as purified rabbit antibodies were treated by various methods, fragmentation, aggregation and complexing with antigen. The ability of the treated and untreated preparations to fix isolated human C1, to activate the classical complement pathway (to consume C4 in normal human serum) were compared. It was found that the different methods affected the conformation of the immunoglobulin molecules in different ways and induced changes to a greater or lesser extent in the two capacities of the preparations tested. In the case of the monoclonal IgM preparation a strong C1-fixation was observed without measurable complement activation. Other preparations, interfacially aggregated human IgG, BSA-anti-BSA and OA-anti-OA immune complexes had a very weak C1-fixing but a marked complement activating capacity. Some preparations, e.g. heat-aggregated IgG, both fixed and activated C1 effectively, aggregates with a complement-activating capacity without C1-fixing effect were separated by gel-filtration. It was demonstrated further, that at a given time only a part of the activated C1 molecules could be found fixed to the immunoglobulins, the other part was released into the fluid phase after activation. On the basis of the results of this and previous studies a hypothesis is proposed suggesting three possible results of the interaction between C1 and the different preparations: (1) firm fixation and activation; (2) binding not followed by activation and (3) a transient binding leading to activation. The possible application of this hypothesis for the interpretation of the results of the different methods for detecting immune complexes is discussed.

Angioedema↗
PubMed1979

Deficient alternative complement pathway activity in newborn sera.

Neonatal susceptibility to overwhelming bacterial infection is commonly attributed to a relative deficiency in serum opsonic activity. However, few studies have compared the functional capacity of the classical complement pathway with that of the alternative complement pathway in the neonate. The opsonic activity of nine maternal infant serum pairs were studied by determining percent uptake of radiolabeled Escherichia coli. Seven mother-infant paired sera were studied using E. coli strains known to be opsonized via the alternative complement pathway: the mean percent uptake of E. coli opsonized in neonatal sera was 16.8%; of those opsonized in maternal sera, 54%; and of those opsonized in control sera, 45% (P less than 0.005). Two E. coli strains requiring the classical complement pathway for opsonization were phagocytized equally well in maternal and infant sera of seven mother-infant pairs. Determination of anti-O hemagglutination inhibition (HI) antibody titers in six maternal sera for one classical complement pathway activating and one alternative complement pathway strain showed no correlation between percent phagocytosis and HI antibody titer. These data would suggest that serum levels of classical pathway components are probably adequate for opsonization of E. coli via the classical pathway, but that low alternative complement pathway activity in neonatal sera may contribute to the newborn's increased susceptibility to bacterial sepsis.

Complement Activation↗
PubMed1975

Activation of the classical and alternate pathways of complement by Corynebacterium parvum.

The immunological adjuvant Corynebacterium parvum has been to activate the alternate pathway of complement in human and guinea-pig serum. Human serum in addition contains anti-C. parvum antibodies leading to activation of the classical complement pathway. The possible role of a C. parvum derived polysaccharide in this activation is considered in relation to the biological effects of the micro-organism.

Agglutination Tests↗
PubMed1992

Inhibition of equine complement activity by polysulfated glycosaminoglycans.

The ability of polysulfated glycosaminoglycans (PSGAG) to inhibit the complement cascade was evaluated. The role of complement in inflammation and infection has been well documented. Inhibition of the complement cascade by PSGAG could explain why intra-articularly administered PSGAG diminish diarthrodial joint inflammation and potentiate septic arthritis in horses. Hemolytic complement testing was performed to evaluate the effect of PSGAG on the equine classical and alternate pathways of complement, using rabbit erythrocytes as the target cells. Concentration of PSGAG between 0.2 mg/ml and 0.6 mg/ml significantly (P less than 0.05) inhibited equine complement in dose-related fashion. Further increase in complement inhibition was not observed at PSGAG concentration greater than 0.6 mg/ml. Difference was not apparent in the extent of inhibition of complement from each of the 4 horses tested. Polysulfated glycosaminoglycans appeared to inhibit the classical and alternate complement pathways equally, indicating possible effect on complement components common to both pathways. Heat inactivation of complement function completely inhibited (P less than 0.01) the hemolytic activity of the serum from all horses.

Animals↗
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↗
PubMed1979

Staphylococcus aureus opsonization mediated via the classical and alternative complement pathways. A kinetic study using MgEGTA chelated serum and human sera deficient in IgG and complement factors C1s and C2.

Staphylococcus aureus opsonization was studied kinetically by: (1) determination of the uptake of [3H]-thymidine labelled bacteria by human PMN's; (2) fluorescent anti-C3 and anti-IgG staining of opsonized bacteria; and (3) measuring bacterial complement consumption. Maximum opsonization in normal serum occurred within 5 min of incubation. About 80% of staphylococci were then taken up by PMN's, and IgG and C3b could be detected on the bacterial surface. In the absence of a functional classical complement pathway, as in sera deficient in C1s and C2 and in MgEGTA chelated serum, maximal opsonization was only achieved after 30--60 min incubation. Opsonization in IgG deficient serum occurred at a rate similar to that found in C2 deficient or MgEGTA chelated serum. Opsonization was greatly enhanced when sera were reconstituted. It was concluded that in IgG deficient serum Staphylococcus aureus opsonization is mediated via the alternative complement pathway. Dilution of normal serum primarily affected the classical complement pathway, resulting in a decreased rate of opsonization. In normal serum IgG did not appear to be a rate-limiting factor. S. Aureus opsonization was best studied by the phagocytosis assay and the fluorescent-antibody technique. Measuring haemolytic complement consumption was found to be an insensitive indicator of bacterial complement activation and opsonization.

Complement Activation↗
PubMed1992

Mechanisms of oligodendrocyte interaction with normal human serum--defining the role of complement.

The interaction of human serum with oligodendroglia was investigated in vitro using purified cultured neonatal rat oligodendrocytes. Previous evidence for antibody independent classical pathway complement activation was confirmed; the results also showed a deficit in the protection of rat oligodendrocytes from complement attack suggesting a deficiency in the expression of terminal regulatory proteins of the complement cascade. Thus, rat oligodendrocytes are selectively sensitive to normal serum due both to complement activation and impaired protection from terminal complement attack.

Animals↗
PubMed1979

Capsular K1 polysaccharide of Escherichia coli: relationship to virulence in newborn rats and resistance to phagocytosis.

The virulence of Escherichia coli strains for newborn rats was related to opsonic requirements of the strains, sensitivity to the bactericidal activity of serum, and K1 capsular polysaccharide content. K1 E. coli strains were more virulent than non-K1 strains after intraperitoneal injection in newborn rats (P less than 0.05) and were more resistant to phagocytosis than non-K1 strains when the classical complement pathway was blocked with Mg-ethyleneglycoltetraacetic acid (P less than 0.0005). Sensitivity to the bactericidal activity of serum was similar among K1 and non-K1 E. coli strains. Two groups of K1 E. coli strains were defined on the basis of opsonic requirements. Group I strains were efficiently opsonized by the alternative complement pathway, while group II strains required the classical complement pathway for opsonization. Group I strains had less detectable K1 polysaccharide in the washed whole cell fraction than group II strains (10.3 versus 18.9 microgram of K1 polysaccharide per 10(10) colony-forming units) and were less virulent than group II strains (mortality, 44 versus 77%, P less than 0.05). The K1 capsular polysaccharide appears to play an important role in determining virulence in newborn rats and opsonic requirements of these strains, but does not contribute to the sensitivity of strains to the bactericidal activity of serum.

Animals↗
PubMed1979

[Consumption hypocomplementemia: comparative value of haemolytic and protein estimations of the components of the classical pathway (author's transl)].

Titrations of total complement (CH50) and of the different components of the classical pathway of the complement system in patients with supposed consumption hypocomplementemia, show that the complement depression involves in an order of decreasing severity hemolytic C4, hemolytic C2, total complement, hemolytic C1, protein C4 and protein C3. These results as well as correlative studies between these different parameters suggest that C4 is the most specific target of activited C1 esterase (C1s). They stress the interest of hemolytic titrations as well as the strong limitations of protein titrations.

Adolescent↗
PubMed1979

Chemotaxigenesis by cell surface components of Staphylococcus aureus.

In an attempt to delineate the staphylococcal cell surface components of importance in chemotaxigenesis, we incubated intact Staphylococcus aureus H, crude cell walls, purified cell walls, peptidoglycan, teichoic acid, and cell membranes with human sera. The results reported indicate that both crude cell walls and purified cell walls, as well as peptidoglycan, were potent chemotaxigens. These particles led to the generation in normal human serum of a factor that was chemotactic for human polymorphonuclear leukocytes. Cell wall peptidoglycan and teichoic acid both appeared to play a role in chemotaxigenesis. Kinetic studies employing C2-deficient serum and immunoglobulin-deficient serum revealed that optimal chemotaxigenesis required the presence of an intact classical complement pathway, as well as antibody. Granulocyte aggregometry studies showed that significant levels of C5a were generated in normal serum and that this activated complement component appears to be a major chemotactic factor produced in serum upon interaction with staphylococcal cell wall components.

Cell Membrane↗
PubMed1992

Classical complement activation induced by pregnancy: implications for management of connective tissue diseases.

AIMS: To determine the effect of pregnancy on C4d concentrations and to assess whether C4d remains a useful disease activity marker in the management of connective tissue diseases during pregnancy. METHODS: Plasma C3, C4, and C4d concentrations were measured in 83 women at various stages of normal pregnancy and compared with those in 80 non-pregnant controls. RESULTS: C3 concentrations in the pregnant women were significantly raised (p = 0.0001) and the C4 concentrations were reduced (p = 0.0007), and accompanied by a significant increase in C4d (p = 0.0001). The C4d:C4 ratio was higher in the pregnant women (p = 0.0001). CONCLUSIONS: Pregnancy induces activation of the classical complement pathway. C4d concentrations cannot be used to monitor disease activity in patients with connective tissue diseases during pregnancy.

Adolescent↗
PubMed1992

Induction of contact sensitivity by cell-associated immunocomplexes requires activation of the early complement components.

Lymph node cells collected from CBA/J mice 4 days after painting the skin with picryl chloride behave like antigen presenting cells and induce contact sensitivity when injected into naive recipient mice. The immunizing capacity of these '4-day' cells is due to T cells which carry on their membrane hapten-IgM immunocomplexes. Incubation of the cells with complement from mouse strains that express high C4 serum levels (C4H), abolishes their immunizing capacity. This effect is related to the activation of the early components of the classical complement pathway, as supported by experiments using C3 and C4-depleted or C5 and C6-genetically deficient mouse sera. The detection of different amounts of C3b and C4b on the surface of 4-day T cells after incubation with C4L and C4H sera supports the possibility that membrane bound activated complement components could modify the immunizing capacity of these cells. Results herein reported suggest that membrane-bound C3b and C4b are not per se inhibitory but interfere with the residual complement activating capacity of 4-day T cells. The role of complement activation by 4-day T cells is pivotal as complement depletion of recipient mice by cobra venom factor (CVF) inhibits the immunizing capacity of untreated 4-day T cells, while 4-day T cells treated with complement in vitro and injected together with C4a anaphylatoxin are able to immunize recipient mice.

Animals↗
PubMed1979

Neonatal cellular and humoral immunity to group B streptococci.

The mechanisms of host resistance to group B streptococci have not been defined precisely. In the studies reported here we have assessed the contributions of both humoral and cellular factors in protection against strains of this group. With assays of specific opsonic activity based upon the production of polymorphonuclear leukocyte chemiluminescence and radiolabeled bacterial uptake, we have demonstrated that specific heat-stable antibody and the classic complement pathway are major factors in opsonization of these organisms. In the absence of specific antibody, fresh serum resulted in markedly reduced bacterial uptake indicating, at best, a minor role for the alternative complement pathway. Additional studies have indicated that strain-specific antiphagocytic factors as well as type-specific ones may play a role in the virulence of these organisms. Neonates who developed group B streptococcal sepsis usually lacked opsonic activity in their infecting strain. In addition, polymorphonuclear leukocytes from normal term and stressed neonates showed impaired metabolic activation as measured in the chemiluminescence assay following exposure to opsonized group B streptococci. These results suggest that neonates who develop group B streptococcal disease may have defects in both the humoral and cellular aspects of their acute inflammatory response which may contribute to the high mortality observed in this most fulminant of bacterial infections.

Antibody Formation↗
PubMed1979

Requirements of immunoglobulin and the classical and alternative complement pathways for phagocytosis and intracellular killing of multiple strains of Gram-negative aerobic bacilli.

The requirements for immunoglobulin and the alternative and classical complement pathways for phagocytosis and intracellular killing of clinical isolates of Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, and Serratia marcescens by normal human polymorphonuclear leukocytes were determined. Human sera deficient in immunoglobulin or classical pathway activity, or both, were compared for their ability to promote phagocytosis os and killing of 13 bacterial strains by the polymorphonuclear leukocytes. Seven of the thirteen microorganisms required immunoglobulin for phagocytosis and killing and utilized only the classical complement pathway. Three required immunoglobulin and utilized both the classical and alternative pathways. The other three microorganisms required minimal immunoglobulin and utilized the alternative or classical pathway, or both. None of the microorganisms utilized the alternative pathway in immunoglobulin-deficient sera or could be forced to utilize this pathway in sera deficient in both immunoglobulin and classical pathway activity. These results demonstrated a heterogeneity in the requirements for immunoglobulin and the alternative and classical complement pathways for phagocytosis and intracellular killing by polymorphonuclear leukocytes among various genera of gram-negative aerobic bacilli, as well as among strains of the same species. In addition, the results suggested that a mechanism of classical pathway activation dependent upon minimal immunoglobulin participates in phagocytosis and intracellular killing of certain gram-negative aerobic bacilli.

Complement Activation↗