Role for phagocytosis in the prevention of neoplastic transformation in Drosophila.

Immunity is considered to be involved in the prevention of cancer. Although both humoral and cellular immune reactions may participate, underlying mechanisms have yet to be clarified. The present study was conducted to clarify this issue using a Drosophila model, in which neoplastic transformation was induced through the simultaneous inhibition of cell-cycle checkpoints and apoptosis.

Inhibitory effects of viral infection on cancer development.

Immune responses evoked on viral infections prevent the dissemination of infection that otherwise leads to the development of diseases in host organisms. In the present study, we investigated whether viral infection influences tumorigenesis in cancer-bearing animals using a Drosophila model of cancer. Cancer was induced in the posterior part of wing imaginal discs through the simultaneous inhibition of apoptosis and cell-cycle checkpoints.

Oral Administration of Edible Seaweed Undaria Pinnatifida (Wakame) Modifies Glucose and Lipid Metabolism in Rats: A DNA Microarray Analysis.

Scope: Wakame is an edible seaweed that is a common constituent in the Japanese diet. Previous studies showed that wakame consumption is associated with the prevention of metabolic syndrome, but the molecular mechanisms underlying the protective effects are poorly understood.

Methods And Results: To determine if the expression of hepatic genes is affected by ingestion of the brown seaweed Undaria pinnatifida (wakame), rats were fed a diet containing 0, 0.

Mechanisms and Significance of Phagocytic Elimination of Cells Undergoing Apoptotic Death.

Cells that have become unwanted by the body need to be selectively, rapidly, and safely removed. The removal of these cells is achieved by apoptosis-dependent phagocytosis: unwanted cells are induced to undergo apoptosis and given susceptibility to phagocytosis. Phagocytes recognize these cells using engulfment receptors that bind substances expressed on the surface of target cells during the apoptotic process.

Signaling pathway for phagocyte priming upon encounter with apoptotic cells.

The phagocytic elimination of cells undergoing apoptosis is an evolutionarily conserved innate immune mechanism for eliminating unnecessary cells. Previous studies showed an increase in the level of engulfment receptors in phagocytes after the phagocytosis of apoptotic cells, which leads to the enhancement of their phagocytic activity. However, precise mechanisms underlying this phenomenon require further clarification.

Peptidoglycan recognition protein-triggered induction of Escherichia coli gene in Drosophila melanogaster.

Interaction between the host and pathogen determines the fate of both organisms during the infectious state. The host is equipped with a battery of immune reactions, while the pathogen displays a variety of mechanisms to compromise host immunity. Although bacteria alter their pattern of gene expression in host organisms, studies to elucidate the mechanism behind this are only in their infancy.

Integrin αPS3/βν-mediated phagocytosis of apoptotic cells and bacteria in Drosophila.

Integrins exert a variety of cellular functions as heterodimers of two transmembrane subunits named α and β. Integrin βν, a β-subunit of Drosophila integrin, is involved in the phagocytosis of apoptotic cells and bacteria. Here, we searched for an α-subunit that forms a complex and cooperates with βν.

Phosphatidylserine recognition and induction of apoptotic cell clearance by Drosophila engulfment receptor Draper.

The membrane phospholipid phosphatidylserine is exposed on the cell surface during apoptosis and acts as an eat-me signal in the phagocytosis of apoptotic cells in mammals and nematodes. However, whether this is also true in insects was unclear. When milk fat globule-epidermal growth factor 8, a phosphatidylserine-binding protein of mammals, was ectopically expressed in Drosophila, the level of phagocytosis was reduced, whereas this was not the case for the same protein lacking a domain responsible for the binding to phosphatidylserine.

Role of NPxY motif in Draper-mediated apoptotic cell clearance in Drosophila.

Draper, a receptor responsible for the phagocytosis of apoptotic cells in Drosophila, possesses atypical epidermal growth factor (EGF)-like sequences in the extracellular region and the two phosphorylatable motifs NPxY and YxxL in the intracellular portion. We previously suggested that Pretaporter, a ligand for Draper, binds to the EGF-like repeat and augments the tyrosine phosphorylation of Draper. In this study, we first tested the binding of Pretaporter to various parts of the extracellular region of Draper and found that a single EGF-like sequence is sufficient for the binding.

Independent recognition of Staphylococcus aureus by two receptors for phagocytosis in Drosophila.

Integrin βν, one of two β subunits of Drosophila integrin, acts as a receptor in the phagocytosis of apoptotic cells. We here examined the involvement of this receptor in defense against infection by Staphylococcus aureus. Flies lacking integrin βν died earlier than control flies upon a septic but not oral infection with this bacterium.

Apoptosis-dependent externalization and involvement in apoptotic cell clearance of DmCaBP1, an endoplasmic reticulum protein of Drosophila.

To elucidate the actions of Draper, a receptor responsible for the phagocytic clearance of apoptotic cells in Drosophila, we isolated proteins that bind to the extracellular region of Draper using affinity chromatography. One of those proteins has been identified to be an uncharacterized protein called Drosophila melanogaster calcium-binding protein 1 (DmCaBP1). This protein containing the thioredoxin-like domain resided in the endoplasmic reticulum and seemed to be expressed ubiquitously throughout the development of Drosophila.

Integrin βν-mediated phagocytosis of apoptotic cells in Drosophila embryos.

To identify molecules that play roles in the clearance of apoptotic cells by Drosophila phagocytes, we examined a series of monoclonal antibodies raised against larval hemocytes for effects on phagocytosis in vitro. One antibody that inhibited phagocytosis recognized terribly reduced optic lobes (Trol), a core protein of the perlecan-type proteoglycan, and the level of phagocytosis in embryos of a Trol-lacking fly line was lower than in a control line. The treatment of a hemocyte cell line with a recombinant Trol protein containing the amino acid sequence RGD augmented the phosphorylation of focal adhesion kinase, a hallmark of integrin activation.

Phagocytic removal of cells that have become unwanted: implications for animal development and tissue homeostasis.

Cells that have become unwanted need to be promptly, selectively, and safely removed. This is made possible by apoptosis-dependent phagocytosis, in which cells unnecessary, obstructive, or dangerous to organisms are induced to undergo apoptosis so that they are earmarked for phagocytosis. The phagocytic elimination occurs so quickly that cells with hallmarks of apoptosis are barely detectable in vivo.

Pretaporter, a Drosophila protein serving as a ligand for Draper in the phagocytosis of apoptotic cells.

Phagocytic removal of cells undergoing apoptosis is necessary for animal development and tissue homeostasis. Draper, a homologue of the Caenorhabditis elegans phagocytosis receptor CED-1, is responsible for the phagocytosis of apoptotic cells in Drosophila, but its ligand presumably present on apoptotic cells remains unknown. An endoplasmic reticulum protein that binds to the extracellular region of Draper was isolated.

Immune response to bacteria in seminiferous epithelium.

The luminal part of the seminiferous epithelium, a tissue compartment protected by the blood-testis barrier, has been considered a site of immune privilege. However, there are reports describing the production of anti-microbial peptides and the expression of Toll-like receptors in cells present in the seminiferous epithelium, evoking the possibility that this tissue compartment is immunologically active at least with regard to the innate immune response. To test this, we injected Escherichia coli into seminiferous tubules of live mice and examined the fate of bacteria, the production of chemokines and inflammatory cytokines, and the infiltration of neutrophils.

Activator protein 1-mediated expression of monocyte chemoattractant protein 1 in cultured rat luteal cells.

We have proposed that luteal cells undergo apoptosis-dependent phagocytosis by invading monocyte-derived macrophages in regressive corpora lutea of the rat. Accumulation of monocytes/macrophages seems to be mediated by monocyte chemoattractant protein 1 (MCP-1) or CCL2, because apoptosis and the production of MCP-1 mRNA occur simultaneously, but in different luteal cells, in a manner dependent on nuclear factor kappaB (NF-kappaB). In this study, we determined the mechanisms underlying the induction of these two events using primary cultures of rat luteal cells.

Perturbation of spermatogenesis by androgen antagonists directly injected into seminiferous tubules of live mice.

Natural and artificial substances present in the environment can affect our health. Testicular toxicants in particular are troublesome, because they disturb gonadal function of males. Translocation of substances into the seminiferous epithelium where sperm production proceeds is restricted due to the blood-testis barrier, but this permeability barrier temporarily disappears under physiological and sub-physiological conditions.

Phosphatidylserine- and integrin-mediated phagocytosis of apoptotic luteal cells by macrophages of the rat.

Corpora lutea disappear from ovaries in the absence of conception. The present study was undertaken to examine the hypothesis that disappearance of corpora lutea is accomplished through apoptosis-dependent phagocytosis of luteal cells. When bone marrow cells expressing green fluorescence protein were transplanted into X-ray-irradiated mice, macrophages derived from donor mice were detected within corpora lutea, suggesting macrophage infiltration into the tissue.

Expression and function of class B scavenger receptor type I on both apical and basolateral sides of the plasma membrane of polarized testicular Sertoli cells of the rat.

Class B scavenger receptor type I (SR-BI), a multiligand membrane protein, exists in various organs and cell types. In the testis, SR-BI is expressed in two somatic cell types: Leydig cells and Sertoli cells. Unlike interstitially localized Leydig cells, Sertoli cells present within the seminiferous tubules keep contact with spermatogenic cells and form the tight junction to divide the seminiferous epithelium into the basal and adluminal compartments.

Phospholipid flip-flop and phospholipid scramblase 1 (PLSCR1) co-localize to uropod rafts in formylated Met-Leu-Phe-stimulated neutrophils.

Movement of phosphatidylserine (PS) to the plasma membrane outer leaflet is a nearly universal marker of apoptosis and occurs during activation of many cells. Neutrophils stimulated with the chemotactic peptide formylated Met-Leu-Phe (fMLP) demonstrated transient PS exposure. Stimulated outward movement of PS was accompanied by enhanced inward movement of several phosphorylcholine lipid probes and was associated with enhanced FM 1-43 staining indicative of phospholipid packing changes.

Concomitant induction of apoptosis and expression of monocyte chemoattractant protein-1 in cultured rat luteal cells by nuclear factor-kappaB and oxidative stress.

It has previously been shown that expression of monocyte chemoattractant protein (mcp)-1 and apoptosis of luteal cells occur concomitantly during the estrous cycle in the rat corpus luteum; however, luteal cells containing mcp-1 mRNA did not seem to be apoptotic. In the present study, the relationship between the induction of apoptosis and mcp-1 expression in cultures of dispersed rat luteal cells was examined. Both apoptosis and mcp-1 expression were spontaneously induced in cultured luteal cells in a manner inhibitable by antioxidative reagents or an inhibitor of nuclear translocation of nuclear factor-kB.

Determination of cell type specificity and estrous cycle dependency of monocyte chemoattractant protein-1 expression in corpora lutea of normally cycling rats in relation to apoptosis and monocyte/macrophage accumulation.

In regressive corpora lutea, apoptosis of luteal cells, expression of monocyte chemoattractant protein-1 (MCP-1), and accumulation of monocytes/macrophages occur. However, whether these three events are correlated and what cell type expresses MCP-1 have yet to be determined. To clarify these issues, we performed histochemical examinations to determine the localization and the numbers of MCP-1 mRNA-containing cells, apoptotic cells, and monocytes/macrophages in corpora lutea of normally cycling rats.

Phosphatidylserine binding of class B scavenger receptor type I, a phagocytosis receptor of testicular sertoli cells.

Testicular Sertoli cells phagocytose apoptotic spermatogenic cells in a manner depending on the membrane phospholipid phosphatidylserine (PS) expressed at the surface of the latter cell type. Our previous studies have indicated that class B scavenger receptor type I (SR-BI) is responsible for the PS-mediated phagocytosis by Sertoli cells. We examined here whether SR-BI binds directly to PS.