Vitronectin-mediated inhibition of complement: evidence for different binding sites for C5b-7 and C9.

In the activated complement system, vitronectin (complement S-protein) occupies the metastable membrane binding site of the nascent precursor complex C5b-7, so that the newly formed SC5b-7 is unable to insert into cell membranes. Some evidence also indicates that vitronectin limits on-going membrane-associated pore formation by inhibiting C9 polymerization. It has been assumed that these two stages of terminal complement complex (TCC) inhibition take place through charge interactions between the heparin-binding region of vitronectin and homologous 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 haemolytic assays. The mode of action of vitronectin in these assays was compared with two 15mer peptides which span residues 348-379 of the heparin-binding region, and a heparin-affinity 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 sulphate did not prevent C5b-7 membrane attachment, but was a potent inhibitor of C9-mediated lysis. The peptides did not inhibit C5b-7 membrane insertion and only one affected 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 takes place through the heparin-binding region.

The value of complement measurements in the assessment of lupus activity.

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.

[Carbon monoxide poisoning in the Brussels metropolitan area. Home survey technics and proposals for action]. / L'intoxication oxycarbonée dans l'agglomération Bruxelloise. Enquêtes techniques à domicile et propositions d'action.

A previous study, preliminary to the organisation of a prevention campaign against carbon monoxide poisoning in Brussels, has confirmed the magnitude of this problem and shown the following two main risk indicators: the "age of the building" and the "nationality of the resident". Therefore, the actions conducted as part of this campaign, were principally focused on run down areas with high concentrations of immigrants. What's more, the possibility has been offered to every diagnosed victim to benefit from a free expertise of his equipment, in order to get a technical diagnosis. The analysis of our data related to all visits conducted from october 87 to april 88 shows that: 1. "resident's nationality" is not a risk factor, strictly speaking. When socio-economic standard is held constant, the risk appears to be identical in all nationalities; 2. most of the victims are underprivileged families; 3. among all apparatuses having been considered responsible for the accidents, around 2/3 are water-heaters; 4. if all kinds of apparatuses are considered, the most frequent faults seems to imply the users' responsibility, lack of maintenance, defective connection with the smoke evacuation system), but for water-heaters, which are responsible for the majority of accidents, the main cause appears to be linked to a defective installation, namely the ventilation of the room not being in accordance with the officials norms.