Decidual endothelial cells express surface-bound C1q as a molecular bridge between endovascular trophoblast and decidual endothelium

This study was prompted by the observation that decidual endothelial cells (DECs), unlike endothelial cells (ECs) of blood vessels in normal skin, kidney glomeruli and brain, express surface-bound C1q in physiologic pregnancy. This finding was unexpected, because deposits of C1q are usually observed in pathologic conditions and are associated with complement activation. In the case of DECs, we failed to detect immunoglobulins and C4 co-localized with C1q on the cell surface. Surprisingly, DECs expressed mRNA for the three chains of C1q and secreted detectable level of this component in serum-free medium. The ability to synthesize C1q is acquired by DECs during pregnancy and is not shared by ECs obtained from endometrium and from other sources. Cell-associated C1q has a molecular weight similar to that of secreted C1q and is released from DECs following treatment with heparinase or incubation at low pH. This suggests that C1q binds to DECs and it is not constitutively expressed on the cell surface. C1q is localized at contact sites between endovascular trophoblast and DECs and acts as an intercellular molecular bridge because adhesion of endovascular trophoblast to DECs was inhibited by antibodies to C1q and to a receptor recognizing its globular portion expressed on trophoblast. © 2008 Elsevier Ltd. All rights reserved

Nutlin-3 differentially modulates miRNA34a and miRNA181 versus miR26a and miR155 in p53 proficient and p53 deficient B chronic lymphocytic leukemia (B-CLL) samples.

The small molecule inhibitor of the MDM2/p53 interaction Nutlin-3 is a promising anti-cancer agent, which exhibits activity against a variety of cancers, including acute myeloid leukemia (AML). Previous studies have shown that Nutlin-3 variably induces apoptosis and cell cycle arrest in cancer cells while it shows low/absent cytotoxicity in normal cells. However, the reason for the selective pro-apoptotic activity in cancer cells with respect to normal counterparts is incompletely understood. In this study, we have compared the induction of several known target genes of p53 in two p53wild-type AML cell lines, OCI-AML3 and MOLM, in comparison with primary normal peripheral blood mononuclear cells (PBMC). Among several p53-target genes activated both in AML cell lines and normal PBMC (BBC3, BAX, MDM2, FAS, CDKN1A, GDF15, GADD45A, TNFRSF10B, TP53I3/PIG3), only TP53I3/PIG3 was selectively activated in MOLM and OCI-AML3, but not in PBMC. The important role of TP53I3/PIG3 in mediating the apoptotic activity of Nutlin-3 was underlined by knock-down experiments with siRNA specific for TP53I3/PIG3, which resulted in a significant decrease in the pro-apoptotic activity of Nutlin-3

Analysis of anti-C1q antibodies in normal and pathological pregnancies

Analysis of anti-C1q antibodies in normal and pathological pregnancies C. Agostinis1, A. Mangogna2, O. Radillo1, G. Ricci1, R. Bulla2. 1. Institute for Maternal and Child Health, IRCCS Burlo Garofolo, 34137, Trieste, Italy; 2. Department of Life Sciences, University of Trieste, 34127, Trieste, Italy. PROBLEM C1q, the recognition molecule of the classical pathway of the complement system plays foundamental roles in pregnancy. C1q has been shown to promote trophoblast endovascular and interstitial invasion and is involved in the clearance of immune complexes and apoptotic bodies. Lack of C1q is characterized by poor trophoblast invasion and pregnancy failure. This molecule can be also the target of an antibody response: anti\u2010C1q antibodies are present in several infectious and autoimmune diseases. The presence of these auto-antibodies has been detected also in 2 to 8% of the general population. The aim of this study was to evaluate the presence and the circulating levels of anti-C1q Ab in pre-eclamptic (PE) patients compared to healthy pregnant women. METHOD Levels of anti\u2010C1q antibodies were analyzed by ELISA in PE and control sera obtained in the first and third trimester of pregnancy. RESULTS Anti-C1q antibodies were detected in both normal and PE sera. Higher levels of these antibodies were present in the first trimester compared to term normal pregnant sera. Early onset PE patients showed higher levels of anti-C1q antibodies compared to late onset PE patients. CONCLUSION Anti-C1q antibody levels increased during the first trimester of pregnancy. The level of these antibodies was higher in the sera of some early onset PE patients. These data indicates a possible role of anti-C1q antibodies in the control of pregnancy and in the pathogenesis of PE. The role played by these antibodies at foeto-maternal interface requires further investigation