Alternative pathway of complement

Prevalence of byssinosis correlates better with airborne endotoxin concentration than with total dust (65). Also, gramnegative bacteria levels in the mill correlate well with disease (66). It has been hypothesized that endotoxins elicit symptoms of byssinosis by activation of both the classical and the alternative pathway of complement with subsequent release of anaphylatoxins, which lead to airway narrowing, and chemotaxins, which cause the influx of PMNs followed by release of lysosomal enzymes and, ultimately, tissue damage. In experiments with guinea pigs using bract, cotton, and gin mill trash extracts, there is a strong correlation between number of PMNs recruited to airways and level of endotoxin (67). 

Recently, other reports have appeared (31). as well as our own studies (32). showing that cotton dust activates the alternate pathway of complement. Previous studies in this laboratory (33.34). showed that antibodies to water extracts of cotton dust, cotton bract, and a highly purified fraction of dust elicited positive immunological responses in rabbits. 

It is also a well established fact that dextran sulfate modulates the immune response with effects on macrophages [119], proliferation of B-lymphocytes [120], and helper T-lymphocytes [121], It has been implicated as an activator of C3 via the alternative pathway of complement [122]. Numerous reports claim that dextran sulfate is a potent inhibitor of human immunodeficiency virus (HIV), Herpes simplex virus (HSV) and other pathogens [123-125]. 

Chonn, A., Cullis, PR., and Devine, D.V. (1991) The role of surface charge in the activation of the classical and alternative pathways of complement by liposomes. Journal of Immunology 146 4234-4241. 

Henry SP, Giclas PC, Leeds J, Pangburn M, Auletta C, Levin AA, Kornbrust DJ. Activation of the alternative pathway of complement by a phosphorothioate oligonucleotide potential mechanism of action. J Pharmacol Exp Therapeut 1997 281(2) 810-6. 

Ling M, Piddlesden SJ, et al. A component of the medicinal herb ephedra blocks activation in the classical and alternative pathways of complement. Clin Exp Immunol 1995 102 582-8. 

Grotendorst, C. A., Carter, R., Rosenberg, R., and Koontz, L. C. (1986). Complement effects on the infectivity of Plasmodium gallinaceum to Aedes aegypti mosquitoes. I. Resistance of zygotes to the alternative pathway of complement. J. Immunol. 136, 4270M274. 

Both subclasses of serum IgA in aggregated form weakly activate the alternate pathway of complement but the structural basis for this function is not understood at the present time. Cell surface Fc receptors for IgA have been reported [83,84],... 

The total ethanolic extract of the stem bark and its main constituent esculin (1) were found practically non-toxic. They inhibited the classical pathway and alternative pathway of complement activation. The total extract and 1 displayed antiinflammatory activity in both zymosan- and carrageenan-induced paw edema in mice. The extract exhibited a pronounced antioxidative activity and caused intense wound epithelization. The antimicrobial and photodynamic damage prevention properties of the extract and its fractions were dependable on their... 

In a number of cases, the drug may also trigger the inflammatory cells also responsible for true allergic reactions by different mechanisms than those involving antibodies or sensitized cells. This is the case, for example, of the direct nonim-munological activation of mast cells (Stanworth 1980) or of the activation of the alternate pathway of complement (Haensch et al. 1980 Voigtlaender et al. 

Caswell CC, Han R, Hovis KM et al. The Sell protein of M6-type group A Streptococcus binds the human complement regulatory protein, factor H and inhibits the alternative pathway of complement. Mol Microbiol 2008 67(3) 584-596. 

Figure 5. Alternative pathway of complement activation amplification loop. Schematic outline of the alternative pathway and the positive feedback loop initiated by C3b. Because of the uncertainty over whether all activating substances utilize the same initial steps, these steps have not been included.

The plot of CL intensity versus time presented in figure 6 shows the effect of varying the quantity of fresh autologous serum used as the source of complement. Zymosan, a boiled, proteolytically digested preparation of yeast cells, was used as the particle to be phagocytosed. Zymosan is well established as an activator of the alternative pathway of complement. Each vial contained an equivalent quantity of zymosan. The differences in the curves of CL therefore reflect the quantity of serum used for opsonification. 

Table 2 - Inhibition of the alternative pathway of complement by phenolic acids and derivatives (1, 7, 8, 9) reduction of haemolysis (%) [14].

Table 3 - IC q values (juM) for flavonoids (10-18) on the classical and the alternative pathway of complement [16].

Hamuro J, Hadding U, Bitter-Suermann (1978) Solid phase activation of alternative pathway of complement by p-l,3-glucans and its possible role for tumor regressing activity. Immunol 34 695-705... 

Gotze O, Miiller-Eberhard HJ (1971) The C3-activation system An alternate pathway of complement activation. J Exp Med 134 905-1085... 

Wilson ME, Morrison DC (1982) Evidence for different requirements in physical state for the interaction of lipopolysaccharides with the classical and alternative pathway of complement. Eur J Biochem 128 137-141... 

Honda S, Sugino H, Asano T, Kakinuma A (1986) Activation of the alternative pathway of complement by an anti-tumor (l->3)-P-D-glucan from Alcaligenes faecalis var. myx-ogenes IFO 13140 and its lower molecular weight and carboxymethylated derivatives. Immunopharmacol 11 29-37... 

Figure 5.4 The Alternative Pathway of Complement Activation. C3 is spontaneously hydrolysed without cleavage of C3a, to become C3b (like). This has the ability to cleave factor B. Combination of C3b (like) with Bb forms a C3 convertase capable of cleaving further C3 into C3b and the anaphylotoxin C3a. Fluid phase C3b is unstable and rapidly inactivated by control proteins, but the availability of a suitable protective surface serves to bind and stabilise the C3b. Stabilisation results in activation of the alternative pathway and constitutes recognition of the protective surface as foreign. C3b can then cleave more factor B to form the true C3 convertase C3bBbP, itself stabilised by the enhancing control protein Properdin (P).

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