Showing papers on "Pore forming protein published in 2010"

Functional dissection of the granzyme family: cell death and inflammation.

Abstract: Cytotoxic lymphocytes rapidly respond and destroy both malignant cells and cells infected with intracellular pathogens. One mechanism, known as granule exocytosis, employs the secretory granules of these lymphocytes. These include the pore-forming protein perforin (pfp) and a family of serine proteases known as granzymes that cleave and activate effector molecules within the target cell. Over the past two decades, the study of granzymes has largely focused on the ability of these serine proteases to induce cell death. More recently, sophisticated mouse models of disease coupled with gene-targeted mice have allowed investigators to ask why granzyme subfamilies are encoded on different chromosomal loci and what broader role these enzymes might play in inflammation and immune response. Here, we provide a brief overview of the granzyme superfamily, their relationship to pfp, and their reported functions in apoptosis. This overview is followed by a comprehensive analysis of the less characterized and developing field regarding the non-apoptotic functions of granzymes.

The battlefield of perforin/granzyme cell death pathways.

Abstract: A pore-forming protein, PRF, and serine proteases, Grz, are key effector molecules of CL. These toxins are stored within secretory granules, which exocytose their contents in response to immune synapse formation between the CL and virus-infected or transformed target cell. There, PRF and Grz synergize to induce various apoptotic death pathways and to maintain immune homeostasis. Mechanistic aspects of the synergy and apoptotic mechanisms are still not fully understood, and the current review will address some of the hotly debated controversies in the field.

Perforin deficiency and susceptibility to cancer

Abstract: Cytotoxic lymphocytes (CLs) are the killer cells that destroy intracellular pathogen-infected and transformed cells, predominantly through the cytotoxic granule-mediated death pathway. Soluble cytotoxic granule components, including pore-forming perforin and pro-apoptotic serine proteases, granzymes, synergize to induce unscheduled apoptosis of the target cell. A complete loss of CL function results in an aggressive immunoregulatory disorder, familial hemophagocytic lymphohistiocytosis, whereas a partial loss of function seems to be a factor strongly predisposing to hematological malignancies. This review discusses the pathological manifestations of CL deficiencies due to impaired perforin function and describes novel aspects of perforin biology.

Perioperative Gene Expression Analysis for Prediction of Postoperative Sepsis

Abstract: Background: Postoperative sepsis is one of the main causes of death after major abdominal surgery; however, the immunologic factors contributing to the development of sepsis are not completely understood. In this study, we evaluated gene expression in patients who developed postoperative sepsis and in patients with an uncomplicated postoperative course. Methods: We enrolled 220 patients in a retrospective matched-pair, case–control pilot study to investigate the perioperative expression of 23 inflammation-related genes regarding their properties for predicting postoperative sepsis. Twenty patients exhibiting symptoms of sepsis in the first 14 days after surgery (case group) were matched with 20 control patients with an uncomplicated postoperative course. Matching criteria were sex, age, main diagnosis, type of surgery, and concomitant diseases. Blood samples were drawn before surgery and on the first and second postoperative days. Relative gene expression was analyzed with real-time reverse-transcription PCR. Results: Significant differences ( P < 0.005) in gene expression between the 2 groups were observed for IL1B (interleukin 1, beta), TNF [tumor necrosis factor (TNF superfamily, member 2)], CD3D [CD3d molecule, delta (CD3-TCR complex)], and PRF1 [perforin 1 (pore forming protein)]. Logistic regression analysis and a subsequent ROC curve analysis revealed that the combination of TNF , IL1B , and CD3D expression had a specificity and specificity of 90% and 85%, respectively, and predicted exclusion of postoperative sepsis with an estimated negative predictive value of 98.1%. Conclusions: These data suggest that gene expression analysis may be an effective tool for differentiating patients at high and low risk for sepsis after abdominal surgery.

Perforin: more than just a pore-forming protein.

Abstract: Cellular apoptosis induced by T cells is mainly mediated by two pathways. One, granule exocytosis utilizes perforin/granzymes. The other involves signaling through death receptors of the TNF-alphaR super-family, especially FasL. Perforin plays a central role in apoptosis induced by granzymes. However, the mechanisms of perforin-mediated cytotoxicity are still not elucidated completely. Perforin is not only a pore-forming protein, but also performs multiple biological functions or perforin performs one biological function (cytolysis), but has multiple biological implications in the cellular immune responses, including regulation of proliferation of CD8+ CTLs.