Initial properdin binding contributes to alternative pathway activation at the surface of viable and necrotic cells.

Properdin, the only known positive regulator of the complement system, stabilizes the C3 convertase, thereby increasing its half-life. In contrast to most other complement factors, properdin is mainly produced extrahepatically by myeloid cells. Recent data suggest a role for properdin as a pattern recognition molecule. Here, we confirmed previous findings of properdin binding to different necrotic cells including Jurkat T cells. Binding can occur independent of C3, as demonstrated by HAP-1 C3 KO cells, excluding a role for endogenous C3. In view of the cellular source of properdin, interaction with myeloid cells was examined. Properdin bound to the surface of viable monocyte-derived pro- and anti-inflammatory macrophages, but not to DCs. Binding was demonstrated for purified properdin as well as fractionated P2, P3, and P4 properdin oligomers. Binding contributed to local complement activation as determined by C3 and C5b-9 deposition on the cell surfaces and seems a prerequisite for alternative pathway activation. Interaction of properdin with cell surfaces could be inhibited with the tick protein Salp20 and by different polysaccharides, depending on sulfation and chain length. These data identify properdin as a factor interacting with different cell surfaces, being either dead or alive, contributing to the local stimulation of complement activation.

The association between presenting complaints and clinical outcomes in emergency department patients of different age categories.

BACKGROUND AND IMPORTANCE: Although aging societies in Western Europe use presenting complaints (PCs) in emergency departments (EDs) triage systems to determine the urgency and severity of the care demand, it is unclear whether their prognostic value is age-dependent. OBJECTIVE: To assess the frequency and association of PCs with hospitalization and mortality across age categories. METHODS: An observational multicenter study using all consecutive visits of three EDs in the Netherlands Emergency department Evaluation Database. Patients were stratified by age category (0-18; 19-50; 51-65; 66-80; >80 years), in which the association between PCs and case-mix adjusted hospitalization and mortality was studied using multivariable logistic regression analysis (adjusting for demographics, hospital, disease severity, comorbidity and other PCs). RESULTS: We included 172 104 ED-visits. The most frequent PCs were 'extremity problems' [range across age categories (13.5-40.8%)], 'feeling unwell' (9.5-23.4%), 'abdominal pain' (6.0-13.9%), 'dyspnea' (4.5-13.3%) and 'chest pain' (0.6-10.7%). For most PCs, the observed and the case-mix-adjusted odds for hospitalization and mortality increased the higher the age category. The most common PCs with the highest adjusted odds ratios (AORs, 95% CI) for hospitalization were 'diarrhea and vomiting' [2.30 (2.02-2.62)] and 'feeling unwell' [1.60 (1.48-1.73)]. Low hospitalization risk was found for 'chest pain' [0.58 (0.53-0.63)] and 'palpitations' [0.64 (0.58-0.71)]. CONCLUSIONS: Frequency of PCs in ED patients varies with age, but the same PCs occur in all age categories. For most PCs, (case-mix adjusted) hospitalization and mortality vary across age categories. 'Chest pain' and 'palpitations,' usually triaged 'very urgent', carry a low risk for hospitalization and mortality.