Biochemistry and Biology of a Leucotactic Binary Serum Peptide System Related to Anaphylatoxin

Abstract
The purification and crystallization of the peptide components of a newly detected binary peptide system in mammalian serum (hog, rat and guinea pig) is described. The peptide system consists of two components, classical anaphylatoxin and cocytotaxin. Cocytotaxin represents a hitherto unknown basic peptide of mammalian serum which has been modified by a contact reaction with immune complexes or other hydrophilic, insoluble substances of high molecular weight. The molecular homogeneity of both crystallized peptides has been established. Classical anaphylatoxin has a molecular weight of 9,500, and cocytotaxin, which is highly similar in its physicochemical behaviour to anaphylatoxin, has a molecular weight of 8,500. Products of an enzymatic reaction with anaphylatoxin and cocytotaxin as substrates have been isolated and characterized as three proteins with molecular weights of 28,000, 56,000 and 112,000. The biological activities of both low molecular peptides were investigated. Anaphylatoxin is a well-known histamine liberator in guinea pigs and elicits anaphylactic reactions. Cocytotaxin, although physicochemically similar to anaphylatoxin, produces none of the actions of anaphylatoxin and has no known separate biological activity. Neither anaphylatoxin nor cocytotaxin display significant chemotactic activity for neutrophils. On recombination and depending on their molar ratio and the absolute concentration of each of the peptides, cell-specific chemotactic activity for neutrophil and eosinophil leucocytes is observed. Cell-specific leucotactic and anaphylatoxin activities could be demonstrated to be different activity phases of the binary peptide system with only a partial overlap. The mechanism of action of this peptide system on cells was evaluated. It was found that cocytotaxin can be replaced by nucleotides such as ATP, cyclic AMP etc., suggesting that cocytotaxin acts as regulatory peptide and that the energy metabolism is activated by anaphylatoxin as catalytic peptide. Considering the pharmacological activities of the three metabolites of the peptides, a relationship between chronic inflammation and circulatory disease may be assumed.