Complement fragment

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. 

C5a is inactivated by the myeloperoxidase-H202 system, which oxidises a methionine residue (Met 70) on the molecule group A streptococcal endo-proteinases also abolish chemotactic activity of C5a and related compounds. Neutrophil lysosomal enzymes (e.g. elastase and cathepsin G) also destroy C5a chemotactic activity, but as these proteases are inhibited by the serum antiproteinases, a -antiproteinase and a2-macroglobulin, the physiological role of neutrophilic proteases in the inactivation of C5a is questionable. Two chemotactic factor inactivators have been found in human serum an a-globulin that specifically and irreversibly inactivates C5-derived chemotactic factors, and a / -globulin that inactivates bacterial chemotactic factors. These activities are heat labile (destroyed by treatment at 56 °C for 30 min) and are distinct from those attributable to anaphylatoxin inactivator. An apparently specific inhibitor of C5-derived chemotactic activity has also been described in human synovial fluid and peritoneal fluid. This factor (molecular mass of 40 kDa) is heat stable and acts directly on C5a. 

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Host-derived (e.g., antigen-antibody complexes, activated complement fragments, inflammatory bile acids, urate crystals, certain androgenic steroid metabolites [e.g., etiocholanolone], certain lymphocyte products)... 

NADPH oxidase is inactive in resting phagocytic cells and is activated upon contact with various ligands (complement fragment C5a, chemotactic peptides, etc)... 

Cl, C2...C9 The 9 main components of complement Cl inhibitor A serine protease inhibitor which inactivates Clr/Cls Clq Complement fragment Iq ClqR Receptor for Clw facilitates attachment of immune complexes to mononuclear leucocytes and endothelium... 

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)... 

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). 

H19. Henson, P. M Larsen, G. L., Webster, R. O., Mitchell, B. C., Goins, A. J., and Henson, J., Pulmonary microvascular alterations and injury induced by complement fragments Synergistic ef-... 

Figure 1.4. Recognition of bacteria by neutrophils. Invading bacteria are opsonised by serum proteins, such as complement fragments (e.g. C3b) and immunoglobulins. The plasma membranes of neutrophils possess receptors for these opsonins (e.g. Fc receptors and complement receptors). Thus, occupancy of these opsonin receptors triggers phagocytosis and activates events such as the respiratory burst and degranulation. Note that the receptors and opsonins are not drawn to scale.

Our data showing normal serum complement levels in cotton mill workers (normal and byssinotic) does not support a complement activation mechanism for the pathogenesis of byssinosis, but the data does not eliminate the possiblity of complement activation in the etiology of byssinosis (Table V). As complement activation is a local reaction, small amounts of complement fragments sufficient... 

Some agents are bifunctional, causing the release of histamine and recruiting leukocytes. Bifunctional mediators include bacterial peptides, endotoxins, DNA, C3a, C5a and bradykinin. Each of these substances can exert dual effects. This may either occur directly, as in the case of bacterial peptides and bradykinin causing chemotaxis and bronchial smooth muscle contraction, or indirectly, as endotoxin and DNA conversion of complement. C3a and C5a act indirectly as complement fragments to effect histamine release, which in turn contracts bronchial smooth muscle. However, both appear to act directly to effect chemotaxis with C5a, the more potent fragment. 

Similar conclusions may be reached from the study of the ligand-induced resistance to proteolysis (47, 53), a phenomenon that has been employed in the production of large complementing fragments of nuclease (see below). 

Complement fragment Csa, which arises from the antibody-antigen reaction. 

Phagocyte surface receptor recogniznig an activated complement fragment fr om C3 Iiidaininatory cytokine released by activated T cells potent activator of inicrogha and leukocytes... 

Hugli TE, Marceau F, Lundberg C (1987) Effects of complement fragments on pulmonary and vascular smooth muscle. Am Rev RespirDis 135 S9-S13. 

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