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

Insulin-like growth factor-I receptor activity is essential for Kaposi's sarcoma growth and survival

Kaposi's sarcoma (KS) is a highly vascular tumour and is the most common neoplasm associated with human immunodeficiency virus (HIV-1) infection. Growth factors, in particular vascular endothelial growth factor (VEGF), have been shown to play an important role in its development. The role of insulin-like growth factors (IGFs) in the pathophysiology of different tumours led us to evaluate the role of IGF system in KS. The IGF-I receptors (IGF-IR) were identified by immunohistochemistry in biopsies taken from patients with different AIDS/HIV-related KS stages and on KSIMM cells (an established KS-derived cell line). Insulin-like growth factor-I is a growth factor for KSIMM cells with a maximum increase of 3H-thymidine incorporation of 130±27.6% (P<0.05) similar to that induced by VEGF and with which it is additive (281±13%) (P<0.05). Moreover, specific blockade of the receptor (either by α IR3 antibody or by picropodophyllin, a recently described selective IGF-IR tyrosine phosphorylation inhibitor) induced KSIMM apoptosis, suggesting that IGF-IR agonists (IGF-I and -II) mediate antiapoptotic signals for these cells. We were able to identify an autocrine loop essential for KSIMM cell survival in which IGF-II is the IGF-IR agonist secreted by the cells. In conclusion, IGF-I pathway inhibition is a promising therapeutical approach for KS tumours

Recurrent pericarditis as an extra-intestinal manifestation of ulcerative colitis in a 14-year-old girl

Pericarditis is a known complication of mesalazine in the treatment of ulcerative colitis. This case study illustrates that after diagnostic work-up, pericarditis should not always be attributed to the use of mesalazine. It may be the presentation of an extra-intestinal manifestation of ulcerative colitis. Restarting of mesalazine should be considered

Differential effects of cytomegalovirus infection on complement synthesis by human mesangial cells

Viruses may be eliminated by the host immune system via complement-mediated lysis of infected cells. Previously, we have demonstrated that the synthesis of complement factor B by renal mesangial cells (MC) is enhanced by interferon-alpha (IFN-α), -β and -γ. In the present study we investigate the effect of human cytomegalovirus (HCMV) infection on the production of complement factors by MC. The production of factor B, C2, C4 and factor H by mock-infected MC was 0.2 ± 0.4, 3.9 ± 6.8, 1.7 ± 0.8 and 149 ± 36 ng/106 cells per 72 h, respectively. In HCMV-infected MC cultures an induction of both factor B and C2 protein synthesis was observed up to 2.2 ± 1.1 and 156 ± 74 ng/106 cells per 72 h, respectively. The synthesis of C4 and factor H of 2.9 ± 2.0 and 146 ± 31 ng/106 cells, respectively, was not altered significantly. By Northern blot and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis it was demonstrated that factor B and C2 mRNA expression were up-regulated in HCMV-infected cell cultures, whereas the levels of C4 and factor H mRNA were not changed. When MC cultures were inoculated with heat- or UV-inactivated HCMV no enhancement of factor B mRNA expression was observed. The enhanced expression was not blocked by phosphono acetic acid (PAA), suggesting that expression of the HCMV immediate early or early genes is sufficient to induce complement synthesis. We conclude that infection of MC cultures with HCMV selectively induces complement C2 and factor B production, probably mediated by interferons

Elevated MBL Levels in Type 1 Diabetic Patients Are Reversed After Simultaneous Pancreas-Kidney Transplantation

Nephrolog

Elevated MBL Levels in Type 1 Diabetic Patients Are Reversed After Simultaneous Pancreas-Kidney Transplantation

Nephrolog

Fibrosis, Not Quantitative NGAL-Staining, in Day-10 Protocol Biopsies Predicts Prolonged Duration of Functional Delayed Graft Function in a Cohort of DCD Kidney Transplant Recipients

Nephrolog