Activation of the Complement System

Significant protection of mice by several polysaccharides other than glucan isolated from S. cerevisiae has been described (209). A 2.16-fold protection in the LD q q is observed for one modifier, MNZ, when given 15 min prior to irradiation. Glucan protects 2.25-fold in this same protocol. Many of these polysaccharides may act through activation of the complement system, rather than directiy on ceHs. 

The mechanisms of the allergy-like reactions to RCM are still a matter of speculation (table 2). Anaphylaxis to RCM has been discussed to be due to a direct membrane effect possibly related to the osmolality of the RCM solution or the chemical structure of the RCM molecule (pseudo-allergy) [2], an activation of the complement system [27], a direct bradykinin formation [28], or an IgE-mediated mechanism [3]. 

Plank C, Mechtler K, Szoka FC Jr, Wagner E (1996) Activation of the complement system by synthetic DNA complexes a potential barrier for intravenous gene delivery. Hum Gene Ther 7 1437-1446... 

CH50 determinations can be used to analyze the total serum complement and are useful for monitoring immune complex diseases (Sullivan, 1989) activation of complement (Table 15.13) in the presence of autoantibodies is indicative of immune complex diseases and autoimmunity. The various components of the complement system (C3, C4) can also be measured to assess the integrity of the system. For instance, low serum concentrations of C3 and C4, with a concomitant decrease in CH50 may indicate activation of complement, while a low C4 alone is a sensitive indicator of reduced activation of the complement system. Since C3 is used as an alternate complement pathway, it usually measures high. Therefore, a low C3 with a normal C4 may indicate an alternate pathway of activation. 

Activation of the Complement System by Antibody-Antigen Complexes The Classical Pathway R. R. Porter and K. B. M. Reid... 

Among the several experimental models available to evaluate the involvement of the complement system [31], the measurement of hemoglobin released from antibody-coated sheep erythrocytes (CH50 test) is frequently selected because of its simplicity. Briefly, the lower the CH50, the higher the activation of the complement system. The CH50 test has been extensively used to compare NS-CA [32]. 

Cascade systems also provide for response to more than one allosteric stimulus in a single pathway. Thus, as shown in Fig. 11-4, glycogen catabolism can be initiated in more than one way. Two pathways are known for initiation of both blood clotting and activation of the complement system. Many pathways activate the MAP kinase pathway shown in Fig. 11-13. 

Figure 31-8 Pathways for activation of the complement system. Active proteases are designated by abbreviations in boldface.

Within the last ten years or so there has been considerable interest in the activation of the Complement system by surface-induced processes. Immunoglobulin of the IgG or IgM class, adsorbed at a surface with the right orientation and spatial ordering... 

About 20 different proteins are included in the complement system Proteins C1-C9, factors B and D, and a series of regulatory proteins. All these proteins are made in the liver, and they circulate freely in the blood and extracellular fluid. Activation of the complement system involves a cascade of proteolytic reactions. In addition to forming membrane attack complexes, the proteolytic fragments released during the activation process promote dilation of blood vessels and the accumulation of phagocytes at the site of infection. 

Nonspecific humoral immunity is mediated via the complement system. After activation of the complement system a cascade is initiated in which more than 15 individual glycoprotein compounds in the plasma react with each other in a... 

Another effector function/mode of action of mAbs is the so-called complement-dependent cytotoxicity or complement-mediated cell death . Activation of the complement system can lead to lysis of the antigen-presenting cell, or can induce inflammation reactions aimed at eliminating these cells efficiently. The successive steps of the complement activation can be summarized in a simplified way [9] ... 

Once deposited, there are multiple mechanisms by which an immune complex initiates an inflammatory reaction (Fig. 2). Foremost among these is activation of the complement system. Immune complexes can activate the classical complement pathway as well as, indirectly or directly, the alternative complement pathway. The biologic activities of complement activation which are relevant to tissue inflammation include the generation of anaphylatoxins C5a and C3a (H29) and chemotactic peptide C5a (H29, T6), direct and indirect membrane lysis by the terminal complement components C56789 (T17), leukocytosis by C3e (G8), macrophage activation by Bb (G12), immune complex solubilization by C3b (C21), and immune adherence, the binding and activation of cells bearing complement receptors. 

Nephritis is an autoimmune disease caused by activation of the complement system. Cinnamon cortex and cinnamon oil inhibited complement formation in vitro. Cinncassiol C, and its glucoside, the cinncassiols C2 and C3 and cinncassiol D, and its glucoside were reported to possess anticomplementary activity. A water-soluble polysaccharide isolated from the cinnamon extract showed complement system activity (Tang and Eisenbrand, 1992). 2-Hydroxycinnamaldehyde and 2-benzyloxy cinnamaldehyde isolated from the stem bark of cinnamon possessed immunomodulatory effects (Koh et al., 1999). 

Humoral immunity Indicators of the existence of humoral immunity are hypergammaglobulinaemia with a predominance of IgM antibodies (321, 436) evidence of circulating immunocomplexes (>80% of cases), also in the bile activation of the complement system. (420) Antibodies were found with the following prevalence SMA (< 1 80) (60%), anticolon antibodies (60%) and ANA (<1 80) (35%). (386, 448) The detection of these antibodies did not correlate with disease activity. 

Senaldi, G., Donaldson, P.T., Magrin, S., Farrant, XM., Alexander, G.X, Vergani, D., Williams, R. Activation of the complement system in primary sclerosing cholangitis. Gastroenterology 1989 97 1430-1434... 

Jatrorrhizine was found to possess anti-inflammatory activity as measured in the cobra venom factor-induced (CVF) rat paw edema. CVF edema was used to examine jatrorrhizine and other substances in order to detect novel compounds, since it has been shown that joint cyclooxygenase and lipoxygenase inhibitors, as well as immunoreactive drugs, exhibit more pronounced inhibitory effects on CVF in comparison to carrageenin-induced edema. CVF edema is dependent on activation of the complement system which plays an important role in acute and chronic inflammatory reactions, mediating the activity of immune complexes. This test system represents a functionally new type of acute inflammation via activation of the alternative complement pathway [290]. 

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