Activation complement

In general, systemic treatment with ASON is well-tolerated and side effects are dose-dependent. Among those, thrombocytopenia, hypotension, fever, increasing liver enzymes, and complement activation were most frequently seen. 

The serine proteases are the most extensively studied class of enzymes. These enzymes are characterized by the presence of a unique serine amino acid. Two major evolutionary families are presented in this class. The bacterial protease subtilisin and the trypsin family, which includes the enzymes trypsin, chymotrypsin, elastase as well as thrombin, plasmin, and others involved in a diverse range of cellular functions including digestion, blood clotting, hormone production, and complement activation. The trypsin family catalyzes the reaction ... 

Arabinofuranosides were removed from PVa, which resulted in an increase in the activity this was in contrast to the findings of Kiyohara et al. [35] who foimd no change in activity after removal of similar units from A. acutiloba pectin. For this polymer it was suggested that the minimum requirement for complement activation via the classical pathway was j6-l,6-linked galactan attached to the rhamnogalacturonan backbone, which also appears to be an important part of the backbone for PVa. 

Other potential adverse effects resulting from liposome administration which need to be studied are undesired complement activation (Cunningham et al., 1979), blood clotting, and pharmacological effects of the lipid components as well as physical obstruction of small capillaries by large particles. 

Hachfeld del Balzo U, Levi R, Polley MJ Cardiac dysfunction caused by purified hiunan C3a anaphy-latoxin. Proc Natl Acad Sci USA 1985 82 886. del Balzo U, Polley MJ, Levi R Cardiac anaphylaxis. Complement activation as an amphfication system. Circ Res 1989 65 847. 

Historical aspects of immunology 4.5.3 Regulation of complement activity... 

Complement activity was first recognized by Bordet, who showed that the lytic activity of rabbit anti-sheep erythrocyte serum was lost on heating to 56°C but was restored by the addition of fiesh serum from an unimmunized rabbit. Thus, two faetors were necessary, a heat-stable factor, antibody, plus a heat-labile factor, complement, whieh is present in all sera. 

Figure 7. Complement activating potency of the ramified region and its neutral oligosaccharides from the pectins of Angelica acutiloba...

Lactoferrin resembles transferrin in terms of molecular weight, amino-acid sequence homology and number of Fe(lII) binding sites. Lactoferrin is released from activated PMNs upon degranulation and may play a role in myelopoiesis, primary antibody response, lymphocyte proliferation, cytokine production and complement activation. 

Abramson, S., Hofistein, S.T. and Weissmann, G. (1982). Superoxide anion generation by human neutrophils exposed to monosodium urate. Effect of protein adsorption and complement activation. Arth. Rheum. 25, 174-180. 

Lue, L.-F. and Rr rs, J. (1992). Full complement activation fails in difiuse plaques of the Alzheimer s disease cerebellum. Dementia 3, 308-313. 

Infections in hemodialysis patients may be related to the choice of membranes, the complement-activating membranes being more deleterious. 

Type II reactions are produced by IgG (or IgM) antibody. The drug or hapten that elicited the antibody response binds to target cells. When antibody binds the drug, complement activation destroys the cell. Blood dyscrasias such as thrombocytopenia and hemolytic anemia are the most common examples of type II reactions. 

TNF (17.5) Monocyte/macrophage, lymphocyte, neutrophil, endothelium, fibroblast, keratinocyte Activation of T and B cells, natural killer cells, neutrophils, and osteoblasts. Stimulation of endothelial cells to release chemotactic proteins, NO and PGI2. Tumoricidal activity. Induces fever, sleep, hepatic acute phase protein synthesis, catabolism, ACTH release. Lead to myocardial depression, hypotension/shock, hypercoagulability, and death. Stimulates production of IL-1, IL-6, IL-8, IFN-y, and H202. Suppression of cytochrome P-450, thyroglobulin, and lipoprotein lipase. Induces complement activation, release of eicosanoids, including PAF. Procoagulant activity. 

The alternative pathway may become activated by lipopolysaccharides, endotoxin (sepsis), virus, fungi, immunoglobulin A-antigen (IgA-Ag) immunocom-plexes, and foreign material. These activate C3, after which the common pathway of complement activation takes place (Fig. 4). There are also a number of inhibitors that regulate and control complement activation. The most important are the Cl-esterase inhibitor (Cl-Inh) and the membrane attack complex inhibitor factor (MACIF CD59). In sepsis a relative deficiency of Cl-Inh has been reported. Administration of Cl-Inh to patients with septic shock attenuates complement acti-... 

Fig. 4. The classical and alternative pathway cascade of complement activation. activation Cl-inh., Cl-esterase inhibitor MACIF, membrane attack complex inhibiting factor (—CD59).

Vascular Effects of Complement Activation. During complement activation a number of complement fragments (anaphylatoxins), which are polypeptides with inflammatory properties, are released. The anaphylatoxins C3a and C5a induce smooth muscle contraction and enhance vascular permeability (H31). The most pronounced activation of complement with the formation of anaphylatoxins and terminal C5-9 complexes has been observed in septic shock (B29, B30, P2). Studies indicate that there is a relation between high concentrations of anaphylatoxins and C5-9 complexes and the development of ARDS or MODS in patients with sepsis (H10). 

Cellular Effects of Complement Activation. C5a is chemotactic for neutrophils, activates their oxidative metabolism, and induces secretion of lysosomal enzymes from the granulocytes and macrophages. C5a may also induce the production of cytokines and prostaglandins (H19, S14). 

The procoagulant factors produced by endothelial cells are the coagulation factors von Willebrand factor (WF), F-V, F-VIII, tissue factor (TF), and plasminogen activator inhibitor (PAI), which blocks the activators u-PA and t-PA and counteracts fibrinolysis (G21, FI6). It has been shown that under the influence of complement activation (C9), in response to endotoxin in vitro (C24), in experimental E. coli sepsis in baboons (D30), and after stimulation with TNF (Al, N6), endothelial cells up-regulate the expression of TF, down-regulate TM and inhibit the production of t-PA and PAF. Thus, the balance may shift in the procoagulant direction with a large excess of PAI-1. 

---