Complement anaphylatoxin

Wetsel, R. A. (1995). Structure, function and cellular expression of complement anaphylatoxin receptors. Curr. Opin. Immunol. 7, 48-53. 

C3bi Inactivated form of C3b fragment of complement C4b Complement fragment 4b (anaphylatoxin)... 

C4BP C4 binding protein plasma protein which acts as co-factor to factor I inactivate C3 convertase C5a Complement fragment 5a (anaphylatoxin)... 

C5aR Receptor for anaphylatoxins C3a, C4a and C5a C5b Complement fiagment 5b (anaphylatoxin)... 

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). 

Serum contains an anaphylatoxin inactivator that is a carboxypeptidase N and cleaves the carboxy-terminal arginine residue to generate C5a des Arg. Thus, following complement activation, C5a des Arg is the predominant... 

C5-derived peptide in serum. This molecule lacks anaphylatoxin activity (i.e. it cannot cause smooth muscle contraction), and its ability to cause che-motaxis in neutrophils is about 10-20 times lower than that of C5a. However, human serum also contains a heat-stable, anionic protein termed co-chemotaxin (relative molecular mass = 60 kDa), which acts in a concentration-dependent manner to permit C5a des Arg to act as a chemoattractant for neutrophils. Thus, C5a des Arg plus cochemotaxin working together probably account for most of the neutrophil chemoattractant activity in vivo following complement activation. The mechanism of action of cochemotaxin is unknown, but it may form a physical complex by attaching to a sialic acid residue on the oligosaccharide chain of C5a des Arg. Deglycosylation of C5a des Arg increases its chemoattractant activity more than 10-fold, and its dependency upon cochemotaxin is decreased. 

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). 

Drugs, particularly organic bases, may release histamine from mast cells by physically displacing the amine from its storage sites. Morphine, codeine, d-tubocu-rarine, guanethidine, and radiocontrast media can release histamine from mast cells. Basic polypeptides, such as bradykinin, neurotensin, substance P, somatostatin, polymyxin B, and the anaphylatoxins resulting from complement activation, also stimulate histamine release. Venoms often contain basic polypeptides as well as the histamine-releasing enzyme phospholipase A. 

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. 

Moghimi, S. M., Hamad, I., Andresen, T. L., Jorgensen, K., and Szebeni, J. (2006), Methylation of the phosphate oxygen moiety of phospholipid-methoxy(polyethylene glycol) conjugate prevents PEGylated liposome-mediated complement activation and anaphylatoxin production, FASEB /., 20, 2591-2593. 

In addition to the examples discussed above, these various reversed-phase HPLC mapping procedures have subsequently found numerous other advocates. Selected recent achievements include application to human hemoglobin variants 9a, 182, 185), the a- and j8-chains of rat hemoglobin 186), polypeptide hormones 9a, 99, 163), porcine C5a anaphylatoxin 187), Aplysia neuroactive polypeptide 188), ACTH/jS-lipotropin precursors 97, 99, 189, 190), oncoproteins 157), chick liver dihydrofolate reductase 191), limulin 192), ATP-citratelyase 193), spore-specific proteins 194), cAMP-dependent protein kinases (/95, 1%), interferons 197), complement components 9a, 198), aj-macroglobulin 198a), lectins 199), phycobiliproteins 200), bovine mitochondrial-F, ATPase 201), collagens, tubulins, and other structural proteins 9a, 202). 

Anaphylatoxin(s) Fragment(s) of complement proteins released during complement activation. 

The complement-derived anaphylatoxin C5a has many prominent immune stimulatory properties and, consequently, is a good candidate for use as a molecular adjuvant. However, its use as such would be severely lunited. Describe the major limitation(s) for the use of natural C5a as a molecular adjuvant. 

C5a the 74-residue anaphylatoxin derived from C5 during complement activation that possesses inflammatory and immune stimulatory properties causing the accumulation of white blood cells at the site of complement activation. 

Gasque P, Chan P, Fontaine M, Ischenko A, Lamacz M, Gotze O, Morgan BP (1995) Identification and characterization of the complement C5a anaphylatoxin receptor on human astrocytes. J Immunol 155 4882-1889. 

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