It has been proposed that the constitutive expression of Fas ligand (FasL) in the eye maintains immune privilege, in part through inducing apoptosis of infiltrating Fas(+) T cells. However, the role of FasL in immune privilege remains controversial due to studies that indicate FasL is both pro- and anti-inflammatory. To ...

It is widely recognized that immune effector mechanisms contribute to cardiac dysfunction in major cardiac pathologies, such as myocarditis and the consequent dilated cardiomyopathy, Chagas' disease and heart transplant rejection. Of the wealth of immune mechanisms known to affect cardiac function, this review will deal with the adverse effects caused ...

Activation of resting T cells usually leads to their proliferation and differentiation into effector cells and a subsequent decline following elimination of the antigen. A situation of excessive antigen density may result in T cell receptor (TCR)-induced deletion of T effector cells, a process termed antigen-induced cell death (AgICD). Previous ...

Fas ligand (FasL) induces apoptotic cell death when bound to Fas antigen. The engagement of FasL has anti-inflammatory effects through the prevention of cell proliferation and cytokine secretion. However, the role of FasL in myocardial ischemia/reperfusion (MI/R) injury is unclear. We examined the expression of FasL mRNA in the myocardium ...

Numerous cytokines and growth factors are synthesized in the endometrium. IL-8 is one of these cytokines regulating endometrial function. It is a neutrophil chemoattractant/ activating factor and a potent angiogenic agent. IL-8 is elevated in the peritoneal fluid of women with endometriosis. We have previously demonstrated a direct proliferative effect ...

PURPOSE: To determine whether long-term cultured nondividing human retinal pigment epithelial (hRPE) cells are sensitive to oxidant-induced apoptosis and whether the Fas pathway is involved in the process. METHODS: Confluent hRPE cells were maintained for 2 to 3 months in the basal medium (DMEM containing 2% fetal bovine serum) with ...

Cytotoxic lymphocytes kill tumor or virus-infected target cells utilizing two mechanisms-(1) release of lytic granules (containing perforin and granzymes), and (2) Fas ligand (FasL)/Fas or TNF-initiated apoptosis. We have examined mechanisms of target cell lysis by effector T cells from gene-targeted and mutant mice using a new Flow Cytometric Cytotoxicity ...

There is considerable evidence that hearing and vestibular function can be influenced by immune processes. The inner ear has evolved mechanisms, such as the blood-labyrinthine barrier that limit immune responses and autoimmune processes to reduce the potential for damage to cochlear cells. Recently, expression of Fas ligand (FasL) in some ...

Apoptotic signalling, particularly in the Fas-Fas ligand (FasL) system, was studied in a mouse osteoblastic cell line, MC3T3-E1. A combination of the cytokines tumour necrosis factor-alpha, interleukin-1beta and interferon-gamma activated the Fas-FasL-dependent cell-death system. The cytokines caused significant enhancement of Fas mRNA and Fas protein, and led to apoptotic cell ...

Apoptosis plays a major role in the development of pathogenesis due to a number of microbial infections. Epithelial cells have been previously shown to die through apoptosis during in vitro infection by the Apicomplexan parasite Cryptosporidium parvum. We now test the possibility that Fas (APO-1/CD95)-dependent apoptosis of uninfected cells, due ...

Photopheresis (ECP) is a novel immunomodulatory therapy effectively used to treat several T-cell-mediated diseases and to reverse allograft rejection after organ transplantation. It consists of infusion of UVA-irradiated autologous leukocytes collected by apheresis and extracorporeally incubated with 8-methoxypsoralen (8-MOP). In this study we explored the potential immunological events for therapeutic ...

Fas ligand (FasL) is a death factor that induces apoptosis in cells bearing its receptor, Fas. Accumulating evidence indicates that the Fas/FasL system is involved not only in apoptosis but also in cell-activation signals. Recently, it was reported that local stimulation of Fas in vivo using an agonistic antibody triggers ...

Our objective was to identify shed placental plasma membrane fragments in the maternal circulation and determine whether these fragments are capable of down-regulating CD3-zeta chain expression and inducing apoptosis in T lymphocytes. Sera, isolated from the blood of pregnant women at 26-29 weeks gestation that subsequently had uncomplicated term deliveries, ...

For centuries, the question of "whether there is life after death" has intrigued the mind of philosophers, and the same question fascinates researchers in the field of apoptosis today. The death of a cell is by no means the end of the story. On the contrary, growing evidence suggests that ...

In gastrointestinal epithelium, metaplastic conversion between predominant cell types is associated with an increased risk of neoplasia. However, the mechanisms regulating metaplastic transitions in adult epithelia are largely undefined. Here we show that matrix metalloproteinase-7 (MMP-7) is expressed not only in the majority of human pancreatic ductal adenocarcinoma specimens, but ...

The induction of immunologic unresponsiveness by i.v. administration of Ag-coupled lymphoid cells has been studied extensively, but the mechanisms remain unclear. We have further explored this model by examining the role of Fas/Fas ligand (FasL)-mediated apoptosis. Using i.v. injection of trinitrophenyl-coupled splenocytes (TNP-spl) as tolerogen, we found that Fas signaling ...

Endothelial Fas ligand (FasL) contributes to the "immune privilege" of tissues such as testis and eye, in which apoptosis is induced in infiltrating Fas-positive activated T cells and results in the inhibition of leukocyte extravasation. In this study, we examined the role of endothelial FasL in controlling cancer cell transmigration ...

Macrophages play an important role in the regulation of malignant tumors. Although glioma contains abundance of macrophages, their role in apoptosis of glioma is not known. We stimulated macrophages with lipopolysaccharide and culture supernatants of activated macrophages were collected to treat glioma cells. The results showed that molecules released from ...

The process of apoptosis is responsible for normal cellular turnover in numerous tissues throughout the body. The endometrial layer of the uterus shows steroid-dependent cyclic changes in structure and function. After a proliferative and secretory phase, steroid support is withdrawn and the uterine epithelium is shed. We hypothesize that the ...

The control of B cell expansion has been thought to be solely regulated by T lymphocytes. We show in this study that Trypanosoma cruzi infection induces up-regulation of both Fas and Fas ligand (FasL) molecules on B cells and renders them susceptible to B cell-B cell killing (referred to as ...

OBJECTIVE: To investigate molecular mechanisms of germ cell apoptosis induced by heat exposure in mice. DESIGN: Controlled laboratory study. SETTING: Departments of Urology and Biochemistry, Yamagata University School of Medicine, Yamagata, Japan. ANIMAL(S): Forty-four male B6D2F1 mice. INTERVENTION(S): Heat exposure, 43 degrees C for 15 minutes. MAIN OUTCOME MEASURE(S): Testicular ...

The survival of leukaemic blasts contributes to the pathological mechanism of acute promyelocytic leukaemia (APL). While treatment of APL using retinoic acid (RA) is a model of differentiation therapy, little is known about possible effects of this treatment on the Fas/FasL system. Investigation of APL cells from patients undergoing differentiation ...

Activation-induced cell death (AICD) is the process by which cells undergo apoptosis in a controlled manner through the interaction of a death factor and its receptor. Programmed cell death can be induced by a number of physiological and pathological factors including Fas (CD95)-Fas ligand (FasL/CD95L) interaction, tumour necrosis factor (TNF), ...

Fas ligand (FasL), a type 2 membrane protein belonging to the TNF family, plays an important role in the induction of cell death. Ligation of Fas receptors by FasL results in apoptosis of the Fas-expressing cell. Autoimmune diabetes results from beta cell destruction by islet-reactive T cells, a process that ...

BACKGROUND: Since the Fas/Fas Ligand (FasL) interaction is recognized as a major pathway of apoptosis in immune cells, we hypothesized that selective expression of FasL by tubular cells (TC) may promote the resolution of interstitial inflammation by inducing apoptosis of infiltrating immune cells. In this study, the effect of FasL ...

The goal of this study was to investigate whether apoptosis occurs in T lymphocytes that invade Fas ligand (FasL)-expressing glioblastomas multiforme (GBMs) and if its induction could be mediated by Fas. Apoptotic T lymphocytes were detected in GBMs by using detection of cell-type markers combined with active caspase-3 immunohistochemical analysis, ...

Microtubule-active drugs, including paclitaxel (Taxol, PTX), cause mitotic arrest, and this can result in apoptosis. A recently study has reported that PTX mediates apoptosis by upregulating FasL in Jurkat and MDA-231 cells. In contrast to the previous report, we found that anti-FasL antibodies failed to inhibit PTX-induced apoptosis in Jurkat ...

The expression of Fas ligand (FasL) in the eye is an important factor in the maintenance of immune privilege. Although FasL expression in donor corneas contributes to prolonged survival of orthotopic corneal allografts in solid organ transplantation, FasL gene-transfected tissues reportedly lead to graft destruction through neutrophil recruitment. Differences in ...

Fas and its ligand (FasL), are a receptor-ligand pair identified as promoting cell death in several tissues. Apoptosis of vascular smooth muscle cells (VSMCs) in human atherosclerotic plaque may contribute to weakening of the fibrous cap, ultimately resulting in plaque rupture. We investigated the ability of monocytes to induce apoptosis ...

We evaluated the effect of single or repeated intraperitoneal daily LPS injections on expression of Fas/FasL system within the brain. Results obtained, utilizing real-time quantitative RT-PCR, show that, while a bolus injection of LPS robustly increases hippocampal Fas, but not FasL, mRNA expression, repeated LPS administrations also induce FasL up-regulation. ...

Interaction between Fas and Fas ligand (FasL) induces apoptotic cell death of Fas-positive cells. Expression of FasL on tumors therefore possibly kills activated Fas-positive cytotoxic T cells that infiltrated into the tumors and consequently the tumors can evade from systemic immune responses. Previous studies however showed that forced expression of ...

The caspase-8 inhibitor c-FLIP blocks death receptor-mediated cell death and plays an essential role in the regulation of lymphocyte homeostasis and the immune escape of tumors. The murine thymoma cell line EL-4 was resistant to Fas ligand (FasL)-induced apoptosis by constitutive expression of FLIP (L). Cycloheximide downregulated the expression of ...

Induction of apoptosis of virus-infected cells is an important host cell defense mechanism. It is well documented that T cells may undergo apoptosis due to interactions between Fas and Fas ligand (FasL). In addition, signals that induce apoptosis in T cells can result from interaction of tumor necrosis factor (TNF)-alpha ...

Fas ligand (FasL) expressing cells delete Fas bearing T cells, thereby enabling privileged immune status in the brain. Although the presence of FasL immunoreactivity has been shown in various cell types in the central nervous system, the precise in vivo distribution of FasL mRNA in mammals is not known. Accordingly, ...

Fas (APO-1/CD95) and its ligand (FasL/CD95L) are cell surface proteins whose interaction activates apoptosis of Fas-expressing targets. In T lymphocytes, the Fas/FasL system regulates activation-induced cell death, a fundamental mechanism for negative selection of immature T cells in the thymus and for maintenance of peripheral tolerance. Aberrant expression of Fas ...

Apoptosis has been proposed as a mechanism for maintaining immune privilege. Expression of Fas ligand (FasL) by the human trophoblast has been recently accepted as a mechanism providing protection against the lytic action of activated decidual immune cells expressing Fas receptor (FasR). Therefore, the purpose of this review was to ...

BACKGROUND AND OBJECTIVES: Sarcoidosis is a systematic granulomatous disorder of unknown origin characterized by accumulation of T lymphocytes and macrophages in multiple organs. We postulated that apoptosis through the Fas/Fas ligand (L) system may be associated with regulation of immune reactions characterized by the formation of noncaseous necrotizing granulomas. Soluble ...

Regional immunoregulatory mechanisms insure that the most effective immune defense mounted is in proportion with preserving unique tissue functionalities. Immune-privileged tissues, such as the eye, are tissue sites of extreme regional immunoregulation. They have evolutionarily adapted several mechanisms to prevent the induction of inflammation within their tissue microenvironment. With over ...

The effects of Shenmai injection (SMI) and aminophylline on apoptosis of small airway smooth muscle cells (SASMC) and the Fas/FasL expression in rats with papain-induced emphysema were investigated. Rat emphysema model was established by a single intratracheal instillation of papain. Apoptosis and Fas/FasL expression of SASMC were detected by immunohistochemistry ...

PURPOSE: Successful engraftment of retinal pigment epithelial cells (RPE) to treat RPE-related retinopathy will depend, at least in part, on controlling the immune response. In order to understand this process we evaluated the fate of RPE xenografts in the subretinal space, anterior chamber, and subcutis of nonimmunosuppressed Royal College of ...

BACKGROUND: Gene-transfer techniques are commonly employed for both in vitro and in vivo studies. However, modifications of the target cell following the introduction of the gene of interest are not often examined. These modifications can alter the immunogenicity and/or the susceptibility of the target cell to apoptosis and may produce ...

BACKGROUND: Drugs can induce different immunologic reactions; T-cell mediated responses produce the most severe reactions. Although in vitro studies show that T cells recognize drugs or their metabolites and induce an effector cytotoxic response, direct in vivo evidence of involvement is lacking. T lymphocytes produce cytotoxic markers that are responsible ...

Since the 19th century, it has been recognized that the anterior chamber of the eye permits the prolonged, and sometimes permanent, survival of foreign tissue and tumor grafts. It was initially believed that the absence of patent lymphatics draining the interior of the eye prevented antigens from reaching regional lymphoid ...

Dysregulated polymorphonuclear leukocyte (PMN) apoptosis and PMN-mediated organ damage have been associated with several medical conditions such as systemic inflammatory response syndrome (SIRS), acute respiratory distress syndrome (ARDS), and ischemia/reperfusion injury. IL-1beta and IL-8 are two cytokines that are elevated under similar conditions. Therefore, we hypothesized that PMN exposed to ...

The major findings regarding corneal allograft rejection in experimental animals are reviewed. The principal anatomic and biological feature of the cornea that determines the immunologic privilege of this tissue is its avascularity. The surgical trauma of transplantation compromises the immunologic privilege, putting corneal allografts at risk for immune rejection. During ...

CD44 is a principal cell surface receptor for hyaluronan, a major component of extracellular matrices. Cells are surrounded by and encounter matrix in vivo, which in turn serves a variety of cell functions through the direct adhesion via their receptors. CD44 communicates cell-matrix interactions into the cell via "outside-in signaling" ...

Immune privilege is a unique strategy developed in several internal organs that can prevent the development of immune attack against these vital organs. One critical mechanism of immune privilege is utilization of Fas/FasL-mediated apoptosis to delete the invading T cells at the immune privilege sites. In this article, we describe ...

Immune privilege is a property of some sites in the body, whereby immune responses are limited or prevented. One explanation that has been proposed for this phenomenon is engagement of the pro-apoptotic molecule Fas by its ligand (FasL), which leads to apoptosis, and consequently limits an inflammatory response. This idea ...

Fas ligand (FasL) is a potent proapoptotic type-II transmembrane protein that can cause cell death in Fas+ target populations. Despite the presumed "silent" nature of apoptotic cell death, forced expression of FasL can induce a dramatic inflammatory response. To elucidate the in vivo mechanism(s) linking FasL and inflammation, we used ...

BACKGROUND: Inappropriately exaggerated response of pulmonary vascular cells to inflammatory mediators may be one mechanism that leads to acute (or adult) respiratory distress syndrome. Nitric oxide (NO) is induced following such exaggerated responses and may have a variety of biological effects, including induction of apoptosis. The mechanism by which NO ...