Pentraxin 3(PTX 3): An Endogenous Modulator of the Inflammatory Response

Inflammatory or anti-inflammatory? That is the question as far as the acute-phase response and its mediators, the pentraxins, are concerned. Only some ten years ago, the classical or short pentraxin C-reactive protein and the newly discovered long pentraxin PTX3 were considered to exert most of the detrimental effects of acute inflammation, whether microbial or sterile in origin. However, accumulating evidence suggests an at least dichotomous, context-dependent outcome attributable to the pentraxins, if not a straightforward anti-inflammatory nature of the acute-phase response. This paper is focused on the inherent effects of pentraxin 3 in inflammatory responses, mainly in coronary artery disease and in Aspergillus fumigatus infection. Both are examples of inflammatory reactions in which PTX3 is substantially involved; the former sterile, the latter infectious in origin. Apart from different inducing noxae, similarities in the pathogenesis of the two are striking. All the same, the introductory question still persists: is the ultimate impact of PTX3 in these conditions inflammatory or anti-inflammatory, paradoxical as the latter might appear? We try to provide an answer such as it emerges in the light of recent findings

MAIA, Fc receptor–like 3, supersedes JUNO as IZUMO1 receptor during human fertilization

Gamete fusion is a critical event of mammalian fertilization. A random one-bead one-compound combinatorial peptide library represented synthetic human egg mimics and identified a previously unidentified ligand as Fc receptor–like 3, named MAIA after the mythological goddess intertwined with JUNO. This immunoglobulin super family receptor was expressed on human oolemma and played a major role during sperm-egg adhesion and fusion. MAIA forms a highly stable interaction with the known IZUMO1/JUNO sperm-egg complex, permitting specific gamete fusion. The complexity of the MAIA isotype may offer a cryptic sexual selection mechanism to avoid genetic incompatibility and achieve favorable fitness outcomes

Transcriptome Analysis Reveals Strain-Specific and Conserved Stemness Genes in Schmidtea mediterranea

The planarian Schmidtea mediterranea is a powerful model organism for studying stem cell biology due to its extraordinary regenerative ability mediated by neoblasts, a population of adult somatic stem cells. Elucidation of the S. mediterranea transcriptome and the dynamics of transcript expression will increase our understanding of the gene regulatory programs that regulate stem cell function and differentiation. Here, we have used RNA-Seq to characterize the S. mediterranea transcriptome in sexual and asexual animals and in purified neoblast and differentiated cell populations. Our analysis identified many uncharacterized genes, transcripts, and alternatively spliced isoforms that are differentially expressed in a strain or cell type-specific manner. Transcriptome profiling of purified neoblasts and differentiated cells identified neoblast-enriched transcripts, many of which likely play important roles in regeneration and stem cell function. Strikingly, many of the neoblast-enriched genes are orthologs of genes whose expression is enriched in human embryonic stem cells, suggesting that a core set of genes that regulate stem cell function are conserved across metazoan species

Pentraxin 3(PTX 3): an endogenous modulator of the inflammatory response. Mediators Inflamm 2012: e920517

Inflammatory or anti-inflammatory? That is the question as far as the acute-phase response and its mediators, the pentraxins, are concerned. Only some ten years ago, the classical or short pentraxin C-reactive protein and the newly discovered long pentraxin PTX3 were considered to exert most of the detrimental effects of acute inflammation, whether microbial or sterile in origin. However, accumulating evidence suggests an at least dichotomous, context-dependent outcome attributable to the pentraxins, if not a straightforward anti-inflammatory nature of the acute-phase response. This paper is focused on the inherent effects of pentraxin 3 in inflammatory responses, mainly in coronary artery disease and in Aspergillus fumigatus infection. Both are examples of inflammatory reactions in which PTX3 is substantially involved; the former sterile, the latter infectious in origin. Apart from different inducing noxae, similarities in the pathogenesis of the two are striking. All the same, the introductory question still persists: is the ultimate impact of PTX3 in these conditions inflammatory or anti-inflammatory, paradoxical as the latter might appear? We try to provide an answer such as it emerges in the light of recent findings

Actual position of interleukin(IL)-33 in atherosclerosis and heart failure: Great Expectations or En attendant Godot?

Atherosclerosis has been recognized as an inflammatory/autoimmune disease. The long-standing low-grade inflammation which fuels its development is primarily focused on the components of the vessel wall. Originally, inflammation in atherogenesis was supposed to be driven by the pro-inflammatory Th1 cellular and cytokine immune response. On the basis of accumulating evidence, this view has been re-evaluated to include the Th17/Th1 axis which is shared by most diseases of sterile inflammation. The anti-inflammatory Th2 cellular and cytokine immune response is initiated concomitantly with the former two, the latter dampening their harmful reactions which culminate in full-blown atherosclerosis. Interleukin-33, a novel member of the IL-1 cytokine superfamily, was suggested to take part in the anti-atherogenic response by mediating the Th1-to-Th2 switch of the immune reactions. However, IL-33 is a multifaceted mediator with both pro- and anti-inflammatory activities, also called a "dual factor" or a "Janus face" interleukin. IL-33 occurs both in an extracellular (cytokine-like) and in a nuclear-bound (transcription factor-like) form, each of them performing distinct activities of their own. This review article presents the latest data relevant to IL-33's role in atherosclerosis and cardiac diseases as perceived by a cardiologist and a cardiac surgeon

Sister kinetochore splitting and precocious disintegration of bivalents could explain the maternal age effect.

Aneuploidy in human eggs is the leading cause of pregnancy loss and Down's syndrome. Aneuploid eggs result from chromosome segregation errors when an egg develops from a progenitor cell, called an oocyte. The mechanisms that lead to an increase in aneuploidy with advanced maternal age are largely unclear. Here, we show that many sister kinetochores in human oocytes are separated and do not behave as a single functional unit during the first meiotic division. Having separated sister kinetochores allowed bivalents to rotate by 90 degrees on the spindle and increased the risk of merotelic kinetochore-microtubule attachments. Advanced maternal age led to an increase in sister kinetochore separation, rotated bivalents and merotelic attachments. Chromosome arm cohesion was weakened, and the fraction of bivalents that precociously dissociated into univalents was increased. Together, our data reveal multiple age-related changes in chromosome architecture that could explain why oocyte aneuploidy increases with advanced maternal age

Inhibitory CD200R and proapoptotic CD95/CD95L molecules on innate immunity cells are modulated by cardiac surgery

INTRODUCTION: Cardiac surgery directly initiates a systemic inflammatory response with the activation of both cellular and humoral parts of the immune system. Exaggerated immune system activation is associated with a risk of life-threatening multi-organ dysfunction (MOD) and increased morbidity and mortality in the postoperative period. The immune system response is regulated and terminated by inhibitory mechanisms, including the regulatory membrane molecules, such as CD200R, CD95, CD95L and soluble sCD200R. METHODS: We measured the expression of CD95, CD95L, CD200R and sCD200R molecules in granulocyte and monocyte populations in blood samples of 30 patients who underwent coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB). Samples collected before surgery, after surgery and in the postoperative period were analyzed by flow cytometry and ELISA. RESULTS: We found a significant increase in the percentage of granulocytes featuring the anti-inflammatory molecule CD200R (from 5% to 17.8%) after surgery. We presume that these cells were less susceptible to apoptosis because they rarely expressed CD95 as the CD200R(+)CD95(-) granulocyte sub-population prevailed. Only a small percentage of CD200R(+) granulocytes expressed simultaneously CD95 (from 0.5 to 2.06 %). This small population of CD200R(+)CD95(+) cells decreased expression of CD200R after surgery and, thus, was likely to be a source of increased sCD200R in serum (from 96 to 294 ng/mL). Also, the expression of CD95L on CD200R(+) granulocytes and CD95 on CD200R(+) monocytes was affected by surgery. The percentage of CD200R(+) monocytes was elevated on the 1(st) postoperative day (from 30.6 to 49.4 %) and dropped below the preoperative value on the 7(th) day after surgery (from 30.6 to 19.8 %). This population comprised mainly CD200R(+)CD95(+) monocytes in which the enhanced expression of CD95 was found. CONCLUSION: Our data show that the expression of CD200R, CD95 and CD95L was influenced by cardiac surgery and imply the role of these membrane molecules in cell regulation-inhibition and apoptosis following cardiac surgery