THE DERIVATION OF TWO DISTINCT ANAPHYLATOXIN ACTIVITIES FROM THE THIRD AND FIFTH COMPONENTS OF HUMAN COMPLEMENT

TLDR

Anaphylatoxin activity was produced by treating C'5 with trypsin or EAC'4, (oxy)2a, 3, and by incubating C'3 with a cobra‑venom protein–beta‑globulin complex that cleaves C'3. Both C'5 and C'3 generate distinct anaphylatoxins: a 9–11 kDa C'5 fragment that contracts smooth muscle, increases vascular permeability, and is antihistamine‑sensitive, and a 6–15 kDa C'3 fragment that elicits similar responses but does not cross‑desensitize with guinea pig anaphylatoxin.

Abstract

Anaphylatoxin activity was derived from both human C'5 and C'3 molecules. This was achieved in the case of C'5 by interaction with trypsin or with EAC'4, (oxy)2a, 3. The smooth muscle-contracting material obtained from the treated C'5 was found to be a fragment of approximately 9,000-11,000 molecular weight. Its action was inhibited with antihistamine. The trypsinized C'5 also increased vascular permeability in guinea pig skin. When human C'3 was incubated with C'3 inactivator complex, which consists of a cobra venom protein and a beta-globulin of human serum, anaphylatoxin activity was observed. The activity was associated with a fragment cleaved from the C'3 molecule, having a molecular weight of between 6,000 and 15,000 as determined by gel filtration techniques. Similar activity was derived from C'3 by the C'3-converting enzyme in free or in cell-bound form. The C'5 anaphylatoxin failed to cross-desensitize guinea pig ileum to the contracting capacities of C'3 and guinea pig anaphylatoxin and vice versa. Anaphylatoxin prepared from C'3 by all methods mentioned above caused cross-desensitization to the other C'3 derivatives, but failed to desensitize to guinea pig anaphylatoxin.