Characterization of the Mr difference between secreted murine fourth component of complement and the major plasma form: evidence for carboxyl-terminal cleavage of the alpha chain.

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Abstract
The .alpha.-chain of murine fourth component of complement (C4) secreted by cells in vitro and in vivo has a MW that is larger by .apprxeq. 4000 than that of the .alpha.-chain of the principal form of C4 is plasma. Using in vivo labeling of C4 with [35S] methionine, C4 was first synthesized with the higher MW (secreted) .alpha.-chain, which was then quickly processed (t1/2 .apprxeq. 1 h) extracellularly to the mature (plasma) C4 possessing the lower MW .alpha.-chain. Both forms of C4 were functional as assayed by the ability of their .alpha.-chains to be cleaved by the protease C1 [activated C1], to bind methylamine and to undergo denaturation-dependent autolysis. When secreted C4 and plasma C4 were activated to C4b, the MW difference of 4000 was maintained in the .alpha.''-chains. The MW difference was localized to the carboxyl-terminal autolytic fragment of the .alpha.-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. An enzyme, presumably a neutral proteinase present in mouse plasma, probably cleaves the carboxyl terminus of newly synthesized C4 .alpha.-chains, creating the major form of C4 in plasma.