MOLECULAR PROPERTIES OF C3 CONVERTING FACTOR (C3 COF)

Abstract

We have recently identified a yet undescribed factor in serum of an 8 year old girl with meningococcal septicemia. This factor caused hypercatabolism of the third component of complement, C3, in vivo and in vitro even in the absence of divalent cations and was termed C3 converting factor C3 CoF. Studies were undertaken to characterize this factor. On gel filtration using HPLC equipment and a TSK SW 4000 blue column two protein-containing fraction of serum were found to be able to induce C3 conversion in vitro: In the IgG-region significant activation of normal C3 occured in the presence of Mg-EGTA but not in EDTA. C3 CoF activity, in contrast, was cofiltrated with IgM. The IgG fraction was isolated from the patient's serum by ammonium sulphate precipitation, anion exchange chromatography and affinity chromatogra phy to apparent homogeneity on immunoelectrophoresis. It had all the properties required to define patient's IgG as C3 nephritic factor C3 NeF and, thus, no longer raised our interest. For the approximately 900 kD protein further biochemical data could be obtained: It is a β2-globulin, precipitable by low ionic strength buffer (=euglobulin), partly heat-resistant at 56°C, requires neither Mg nor Ca and cannot be inhibited by soy bean trypsin inhibitor at 5 mg/ml. This is, to our knowledge, the first case where two different activators of C3 simultaneously occur, one with known properties (C3 NeF) and one yet undescribed (C3 CoF).