SUMMARYIn liie activated complement system, vitronectin (complement S-protcin) occupies ihe metastabie membrane binding site of the nascent precursor compiex C5b-7, so that the newly formed SC5b-7 is unable to insert into celi membranes. Some evidence also indicates that vitronectin limits on-going membrane-associated pore ibrmation by inhibiting C9 poiynierization. It has been assumed that these two stages of terminal complement complex (TCC) inhibition taice piace through charge interactions between the heparin-binding region of vitronectin and homoiogous cysteine-rich sequences of the late complement proteins C6, C7, C8 and C9. We examined SC5b-7 formation and inhibition of C9 binding in the TCC using separate haemolylie assays. The mode of action of vitronectin in these assays was compared with iwo 15mer peptides which span residues .148-379 of ihe heparin-binding region, and a heparin-atlinity polypeptide. protamine sulphate. The results showed that vitronectin acts predominantly through SC5b-7 production with a lesser effect on the inhibition of C9 lytic pore formation, in contrast, protamine suiphate did not prevent C5b-7 membrane attachment, but was a potent inhiiiitor of C9-mediated lysis. The peptides did not inhibit C5b-7 membrane insertion and only one aiTeeted C9 binding. These data suggest that the two stages of TCC inhibition involve separate binding sites on the vitronectin molecule. The site for association with nascent C5b-7 is unknown, whereas inhibition of C9 binding and pore formation taices place through the heparin-binding region.

The complement system was studied prospectively in 29 patients, predominantly renal (25), with systemic lupus erythematosus (SLE) to examine the value of complement assays in the distinction between active and inactive disease. Disease activity was evaluated primarily by clinical, biochemical and histological parameters which were obtained at the time of assessment. Fourteen patients had active disease, as assessed by clinical and laboratory criteria. C1q, C4, C4a, C2, C3, C3a, C5, total haemolytic activity (CH50) and complement inhibitors were measured in each patient. The ratios of C4a:C4 and C3a:C3 were also calculated. Values for all components except C5 were different between control subjects and active patients while only CH50 was different between inactive patients and controls. All parameters except C4a:C4 and C5 were different between active and inactive patients. There was a highly significant difference in the number of active patients with reduced levels of C2, C3 and C3a:C3 compared to inactive patients (i.e. p less than 0.001) whereas lesser or no difference was observed for other parameters. The concentration of complement inhibitors was elevated in both groups. We conclude that, among readily available complement parameters, C2 and C3 provide the best assessment of disease activity in patients with SLE.