Anaphylatoxin inactivator

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... 

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. 

This enzyme [EC 3.4.17.3] (also referred to as lysine carboxypeptidase, arginine carboxypeptidase, kininase I, or anaphylatoxin inactivator) is a zinc-dependent member of peptidase family M14. The enzyme hydrolyzes the peptide bond at the C-terminus provided that the C-terminal amino acid is either arginine or lysine. The enzyme inactivates bradykinin and anaphylatoxins in blood plasma. 

Anaphylatoxin inactivator (carboxypeptidase N) 310,000 Protease, Inactivates C3a and C5a anaphylatoxins by cleavage of X-Arg peptide bond... 

The human plasma metallo-protease carboxypeptidase N (CPN, arginine carboxypeptidase, anaphylatoxin inactivator, kininase I, EC 3.4.17.3) catalyzes the release of the basic amino acids lysine and arginine from the C-termini of peptides and proteins such as bradykinin and kallidin [95], the anaphylatoxins C3a, C4a, and C5a [96,97], fibrinopeptides 6A and 6D [98], hexapeptide enkephalins [99], protamine [100], and the creatine kinase MM-isoenzyme [101,102]. Its most likely physiological function is to protect the organism from the actions of potent peptides, which may escape from tissues or be released in the circulation. 

V. A. Bokish and H. J. Miiller-Eberhard. Anaphylatoxin inactivator of human plasma its isolation and characterization as a caiboxypeptidase. J. Clin. Invest. 49 2427-2436 (1970). 

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)... 

P (properdin) can also bind to the C3 convertase. Its role is to stabilize the complex and hence it is considered a cofactor-activator in the alternative pathway. These components plus additional C3b molecules form the C5 convertase, an enzyme complex that peoteolytically converts C5 to C5a and CSb. Properdin stabilizes C3b and Bb in the complex and protects these proteins from proteolytic inactivation by factor I. Factor H competes for Bb in the C5 convertases, the same as it does in the C3 convertase. The alternative pathway has also been called the properdin pathway because of properdin s participation in alternative pathway C3 and C5 convertases. C5b is a component in the terminal complex of the complement activation process, the MAC. The MAC is composed of a self-assembled, noncovalent complex of C5b, C6, C7, C8, and C9. Together these components produce a pore-like structure that makes the membrane of the cell to which it is attached permeable and causes cell death. Under the electron microscope the MAC appears like an impact crater similar to those observed on the surface of the moon. C5a is also an anaphylatoxin like C3a, but it is more potent. C5a is also a chemokine and attracts phagocytic cells to the site of complement activation. 

Another possible function of C2 is in relation to the liberation of a kinin mediator (C-kinin) in the serum of patients with HANE (Donaldson et aL, 1969, 1970). It was found that HANE results from a severe deficiency of the Cl-INH protein or from structurally abnormal and functionally inactive Cl-INH (Donaldson et aL, 1963 Harpel et al, 1975). Thus activated Cl is increased in the serum of these patients, and on incubation a dialyzable and heat-stable mediator is released which increases vascular permeability and contracts smooth muscle without causing tachyphylaxis. The activity was inactivated by carboxypeptidase B and, unlike bradykinin, by trypsin, suggesting that the active principle is a polypeptide distinct from bradykinin, C3a and C5a anaphylatoxins (Donaldson et al, 1969). The liberation of this activity required Ci, C4, and C2 and was inhibited by added Cl-INH or antiserum to C4 or C2 but not by anti-C3 (Donaldson et al, 1969, 1970). In addition, the active principle was detected in the incubation mixture of refined ( s, C4, and C2 (Klemperer et al, 1969). Intradermal injection of active Cls increased vascular permeability in normal but not in C2-deficient patients (Klem-... 

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