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.</p

THE PREV A LENCE OF AN TI BOD IES AGAINST EQUINE IN FLU ENZA VI RUS, EQUINE HERPESVIRUS 1 AND 4, EQUINE ARTERITIS VI RUS AND EQUINE RHINOVIRUS 1 AND 2 IN DUTCH STAN DARD BRED HORSES

Pre va len tie van an ti stof fen te gen equi e ne in flu en za vi rus, equi e ne her pes vi rus 1 en -4, equi ABSTRACT A ran dom cross-sec ti o nal se ropre va len ce stu dy was con duc ted in 1996 by ta king blood sam ples from 330 dif fe rent Stand ard bred hor ses on all ra cet racks in the Ne ther lands. This blood sam pling took pla ce on four con se cu ti ve days, with each hor se being sam pled only once. Sam ples were in ves ti ga ted for an ti bo dies against se ver al strains of equi ne in flu en za vi rus, equi ne her pes vi rus ty pes 1 and 4, equi ne ar te ri tis vi rus, and equi ne rhi no vi rus ty pes 1 and 2. A type spe ci fic gG ELISA was used to de ter mi ne spe ci fic se ropre va lences of equi ne her pes vi ru ses 1 and 4. Influ en za se ro lo gy, using in flu en za A/equi/1/Pra gue/56 as an in di ca tor vi rus for vac ci na ti on, de mon stra ted that 38% of the hor ses were eit her un vac ci na ted or in ade qua te ly vac cina ted. Many of the se hor ses ap pe a red to have ex pe rien ced an in flu en za A/equi-2 field in fec ti on. Neut ra lizing and com ple ment fixing an ti bo dies against both EHV1 and EHV4 were found in a high per cen ta ge of the sam ples. Ho we ver, for EHV1 this high se ropre va len ce was pu ta ti ve ly cau sed by cross-re ac ting EHV4 an ti bo dies sin ce, in a type-spe ci fic gG ELISA, the EHV1 se ropre va len ce was only 28%, as com pa red with a 99% se ropre va len ce for EHV4. High se ropre va len ces were also found for equi ne rhi no vi rus type 1 and for the equi ne ar te ri tis vi rus, thus in di ca ting the en de mic na tu re of the se vi ru ses. Many of the se in fec ti ons may be sub cli ni cal. The se ropre va len ce of equi ne rhi no vi rus type 2 was sur pri sing ly low. The pos si ble re la ti onship be tween vi ral in fec ti ons and up per res pi ra to ry tract dis e a se and/or in flam ma to ry air way dis e a se is discus sed. SAMENVATTING Een ge ran do mi seerd &apos;cross-sectional&apos; se ropre va len tie on der zoek werd uit ge voerd bij warm bloed paar den (n=330) op alle draf-en ren ba nen in Ne der land door het een ma lig ne men van een bloed staal op vier op een vol gen de da gen. De se rum sta len wer den on der zocht op an ti stof fen te gen ver schei de ne equi e ne in flu en zas tam men, equi e ne her pes vi rus type 1 en 4, equi e ne ar te ri tis vi rus en rhi no vi rus type 1 en 2. Voor het be pa len van de af zon der lij ke seropre va len tie van EHV1 en EHV4 werd een ty pes pe ci fie ke gG ELISA ge bruikt. De in flu en zas ero lo gie op ba sis van in flu en za A/equi-1/Praag/56 als in di ca tor vi rus toon de aan dat 38 % van de paar den niet of on vol doen de gevac ci neerd was. Veel van deze paar den ble ken wel een in flu en za A/equi-2 veld in fec tie te heb ben door ge maakt. In een hoog per cen ta ge van de sta len wer den neu tra li se ren de en com ple ment bin den de an ti stof fen te gen EHV1/4 aang etoond. Voor EHV1 werd deze hoge se ropre va len tie waar schijn lijk ver oor zaakt door kruis re a ge ren de an tiVlaams Dier ge nees kun dig Tijd schrift, 2005, 74, 140-145 Ori gi nal Arti cle 140 stof fen te gen EHV4, de se ropre va len tie van 28 % te gen EHV1 en 99 % te gen EHV4 in een ty pes pe ci fie ke gG ELISA in acht ge no men. Ge zien de re la tief hoge se ropre va len ties die bij de Ne der land se warm bloed po pu la tie gevon den wer den, moe ten hier ook equi e ne rhi no vi rus type 1 en equi e ne ar te ri tis vi rus als en zo ötisch wor den beschouwd . Veel van deze in fec ties lij ken sub kli nisch te ver lo pen. De se ropre va len tie van equi e ne rhi no vi rus type 2 was ver ras send laag. In de dis cus sie wordt aan dacht be steed aan het mo ge lij ke ver band tus sen vi ra le in fec ties en ziek te ver schijn se len van de bo ven ste lucht we gen

What Values in Design? The Challenge of Incorporating Moral Values into Design

Recently, there is increased attention to the integration of moral values into the conception, design, and development of emerging IT. The most reviewed approach for this purpose in ethics and technology so far is Value-Sensitive Design (VSD). This article considers VSD as the prime candidate for implementing normative considerations into design. Its methodology is considered from a conceptual, analytical, normative perspective. The focus here is on the suitability of VSD for integrating moral values into the design of technologies in a way that joins in with an analytical perspective on ethics of technology. Despite its promising character, it turns out that VSD falls short in several respects: (1) VSD does not have a clear methodology for identifying stakeholders, (2) the integration of empirical methods with conceptual research within the methodology of VSD is obscure, (3) VSD runs the risk of committing the naturalistic fallacy when using empirical knowledge for implementing values in design, (4) the concept of values, as well as their realization, is left undetermined and (5) VSD lacks a complimentary or explicit ethical theory for dealing with value trade-offs. For the normative evaluation of a technology, I claim that an explicit and justified ethical starting point or principle is required. Moreover, explicit attention should be given to the value aims and assumptions of a particular design. The criteria of adequacy for such an approach or methodology follow from the evaluation of VSD as the prime candidate for implementing moral values in design

Heparanase Levels Are Elevated in the Urine and Plasma of Type 2 Diabetes Patients and Associate with Blood Glucose Levels

Heparanase is an endoglycosidase that specifically cleaves heparan sulfate side chains of heparan sulfate proteoglycans. Utilizing an ELISA method capable of detection and quantification of heparanase, we examined heparanase levels in the plasma and urine of a cohort of 29 patients diagnosed with type 2 diabetes mellitus (T2DM), 14 T2DM patients who underwent kidney transplantation, and 47 healthy volunteers. We provide evidence that heparanase levels in the urine of T2DM patients are markedly elevated compared to healthy controls (1162±181 vs. 156±29.6 pg/ml for T2DM and healthy controls, respectively), increase that is statistically highly significant (P<0.0001). Notably, heparanase levels were appreciably decreased in the urine of T2DM patients who underwent kidney transplantation, albeit remained still higher than healthy individuals (P<0.0001). Increased heparanase levels were also found in the plasma of T2DM patients. Importantly, urine heparanase was associated with elevated blood glucose levels, implying that glucose mediates heparanase upregulation and secretion into the urine and blood. Utilizing an in vitro system, we show that insulin stimulates heparanase secretion by kidney 293 cells, and even higher secretion is observed when insulin is added to cells maintained under high glucose conditions. These results provide evidence for a significant involvement of heparanase in diabetic complications