The α-chain of murine fourth component of complement (C4) secreted by cells in vitro and in vivo has a M(r) that is larger by ~4,000 than that of the α-chain of the principal form of C4 in plasma. By using in vivo labeling of C4 with [35S]methionine C4 was shown to be first synthesized with the higher M(r) ('secreted') α-chain, which was then quickly processed (t(1/2)~1 hr) extracellularly to the mature ('plasma') C4 possessing the lower M(r) α-chain. Both forms of C4 were functional as assayed by the ability of their α-chains to be cleaved by the protease C1̄, to bind methylamine, and to undergo denaturation-dependent autolysis. When secreted C4 and plasma C4 were activated to C4b, the M(r) difference of 4,000 was maintained in the α'-chains. The M(r) difference was localized to the carboxyl-terminal autolytic fragment of the α-chain and was unaffected by the removal of carbohydrate. C4 from resident peritoneal macrophage cultures could be converted to the plasma form by incubation with heparin/plasma. This conversion could be blocked by EDTA or 1,10-phenanthroline. These data suggest that an enzyme, presumably a neutral proteinase present in mouse plasma, cleaves the carboxyl terminus of newly synthesized C4 α-chains, thereby creating the major form of C4 in plasma.
|Original language||English (US)|
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Issue number||21 I|
|State||Published - 1982|
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