Interaction between LPS-induced NO production and IDO activity in mouse peritoneal cells in the presence of activated Vα14 NKT cells

In this study, we demonstrated that lipopolysaccharide (LPS) markedly increased nitric oxide (NO) production and indoleamine 2,3-dioxygenase (IDO) activity in mouse peritoneal cells in the presence of activated Vα14 natural killer T cells. Moreover, LPS-induced NO production in peritoneal cells from IDO-knockout (KO) mice was more increased than that from wild-type mice. However, there was no significant difference in the expression of inducible nitric oxide synthase (iNOS) mRNA and protein between the wild-type and IDO-KO mice. No significant difference was also observed in the ratio of CD3- and DX5-positive cells and F4/80- and TLR4-positive cells in peritoneal cells between the wild-type and IDO-KO mice. Since the IDO activity was enhanced by an NO inhibitor, NO may be post-translationally consumed by inhibiting the IDO activity. IDO is well known to play an important role in immunosuppression during inflammatory disease. Therefore, the inhibition of IDO by NO may exacerbate inflammation in the peritoneal cavity.     

Diurnal rhythm of hypophyseal cells in mice. IV. Pars Distalis∗

Abstract

Using various staining techniques and methods, the following cells were differentiated from pars distalis of the pituitary gland in the mouse: corticotropic, somatotropic, lactotropic, thyrotropic and gonadotropic cells.

Diurnal activity of the differentiated cells in pars distalis of the pituitary gland was determined by the method of karyometry.

The karyometric analysis showed the existence of a distinct diurnal rhythm in nuclear volume in all five types of the differentiated cells in both sexes.     

Vα14 NKT cells activated by alpha-galactosylceramide augment lipopolysaccharide-induced nitric oxide production in mouse intra-hepatic lymphocytes

Vα14 natural killer T (Vα14 NKT) cells activated by α-galactosylceramide (α-GalCer) secrete a large amount of Th1 and Th2 cytokines. IFN-γ plays a crucial role in the inflammation response, and is also known as an activator of nitric oxide (NO) production. We previously reported that lipopolysaccharide (LPS)-induced NO production is augmented by α-GalCer in mouse peritoneal cells. Since the liver is susceptible to LPS stimulation via the portal vein, we examined the effect of α-GalCer on LPS-induced NO production in murine intra-hepatic lymphocytes (IHLs). Although IHLs augmented LPS-induced NO production by α-GalCer administration, such an augmentation was not observed in non-treated mice. Furthermore, α-GalCer did not augment LPS-induced NO production in IHLs from IFN-γ knockout mice. In flow cytometry analysis of IHLs from α-GalCer-treated mice, the ratio and number of F4/80- and TLR4-positive cells rose as compared with non-treated mice. The liver injury may be induced by LPS and NO under the condition where Vα14 NKT cells were activated.     

IL-4 inducibility in NKT cells,naïve CD4<Superscript>+</Superscript> T cells and TCR-γ δ T cells

NKT cells, na?ve CD4(+) T cells, and TCR-gammadelta T cells belong to distinct T cell lineages but all express T cell receptors generated through random combinatorial joining of V-(D)-J genes. These distinct lineage T cells also possess the property of promptly activating the IL-4 gene upon T cell receptor stimulation. A comparative accounting of features as they pertain to IL-4 inducibility in these three distinct lineage T cells is provided here.     

Genomic instability in mammalian cell hybrids. IV. Is mutation frequency elevated in hybrid cells?

In this study, we set out to determine whether the mutation frequency in cell hybrids is increased over the frequencies in the two parental lines, and whether this increase is related to the evolutionary divergence of the cell parents. Two test loci were chosen: forward mutation at the HPRT locus and mutation to resistance to the drug emetine. We conclude that while some cell combinations do seem to produce hybrids with higher mutation frequencies, this is not consistently so, and, indeed, mutation rates in hybrids may be higher, lower or very similar to rates in the parental lines. Further, evolutionary divergence between the parental lines does not appear to correlate to mutation frequency in the hybrids.     

Tumour-initiating cells vs. cancer 'stem' cells and CD133: what's in the name?

Recent evidence suggests that a subset of cells within a tumour have 'stem-like' characteristics. These tumour-initiating cells, distinct from non-malignant stem cells, show low proliferative rates, high self-renewing capacity, propensity to differentiate into actively proliferating tumour cells, resistance to chemotherapy or radiation, and they are often characterised by elevated expression of the stem cell surface marker CD133. Understanding the molecular biology of the CD133(+) cancer cells is now essential for developing more effective cancer treatments. These may include drugs targeting organelles, such as mitochondria or lysosomes, using highly efficient and selective inducers of apoptosis. Alternatively, agents or treatment regimens that enhance sensitivity of these therapy-resistant "tumour stem cells" to the current or emerging anti-tumour drugs would be of interest as well.     

α-Galactosylceramide-induced airway eosinophilia is mediated through the activation of NKT cells

Invariant NKT (iNKT) cells bridge innate and adaptive immune responses, resulting in the expansion of Ag-specific B and T cell responses. α-Galactosylceramide (α-GalCer), the most studied glycolipid that activates iNKT cells, has been proposed to be an effective adjuvant against infections and tumors. We found that the activation of iNKT cells by intranasal injection of α-GalCer induced airway eosinophilia in naive mice. Eosinophils, which mediate tissue damage and dysfunction by secreting mediators, play important roles in the pathogenesis of allergic diseases. In this study, we investigated the mechanism of how eosinophils are recruited to the lung by α-GalCer. Our results demonstrated that α-GalCer-induced eosinophil inflammation was mediated through iNKT cells. These cells secreted IL-5 to recruit eosinophils directly to the lung and/or secreted IL-4 and IL-13 to recruit eosinophils indirectly by inducing lung epithelial cells, endothelial cells, and fibroblast to secrete the eosinophil chemoattractant eotaxin. In addition, in the OVA-alum murine model of allergic asthma, α-GalCer administration in OVA-immunized mice also increased airway eosinophilia after challenge. Given our findings, intranasal administration of α-GalCer induced airway eosinophilic inflammation in both naive and allergic mice. Hence, it remains to be determined whether the activation of iNKT cells would be applicable in therapeutics for human diseases.     

Chemiluminescence in neutrophils and Lettré cells induced by myxoviruses.

Luminol-mediated chemiluminescence in neutrophils is stimulated by Sendai virus and by influenza virus; Lettré cells also exhibit chemiluminescence (less than 10% of that of neutrophils), which is stimulated by Sendai virus and by influenza virus. Virally induced permeability changes are not responsible for chemiluminescence, since (i) extracellular Ca2+ inhibits permeability changes but stimulates chemiluminescence, and (ii) influenza virus, which induces permeability changes at pH 5.3 but not at pH 7.4, induces chemiluminescence at either pH. Other agents [zymosan, N-formyl-L-methionyl-L-leucyl-L-phenylalanine, 4-phorbol 12-myristate 13-acetate (phorbol ester), A23187] likewise induce chemiluminescence in the absence of permeability changes.     

Transfer cells in the sporophyte — gametophyte junction ofPhyscomitrium cyathicarpum Mitt.

Summary Ultrastructural investigations reveal the presence of transfer cells in tissues belonging to both generations at the sporophyte-gametophyte junction. The foot epidermal cells possess an organelle-rich cytoplasm whereas cells of the vaginula contain more elaborate wall labyrinth. Also visible are differences in the extent of retraction of cytoplasm in these two types of cells.     

Progress in spondylarthritis. Immunopathogenesis of spondyloarthritis: which cells drive disease?

Spondyloarthritides, or SpA, form a cluster of chronic inflammatory diseases with the axial skeleton as the most typical disease localisation, although extra-articular manifestations such as intestinal inflammation may frequently occur during the course of the disease. This review summarises recent progress in our understanding of the immunopathogenesis of SpA with special emphasis on the cellular constituents considered to be responsible for the initiation and/or perpetuation of inflammation. There are several arguments favouring a role for haematopoietic cells in the pathophysiology of spondyloarthritis, including HLA-B27-associated dendritic cell disturbances, HLA-B27 misfolding properties and T helper 17 cells. In addition, recent studies have pointed toward a pivotal role for stromal cells. A major challenge, however, remains to determine how recently identified genetic associations such as interleukin-23 receptor polymorphisms may influence cellular targets in spondyloarthritis.     

Temporal filtering in retinal bipolar cells. Elements of an optimal computation?

Recent experiments indicate that the dark-adapted vertebrate visual system can count photons with a reliability limited by dark noise in the rod photoreceptors themselves. This suggests that subsequent layers of the retina, responsible for signal processing, add little if any excess noise and extract all the available information. Given the signal and noise characteristics of the photoreceptors, what is the structure of such an optimal processor? We show that optimal estimates of time-varying light intensity can be accomplished by a two-stage filter, and we suggest that the first stage should be identified with the filtering which occurs at the first anatomical stage in retinal signal processing, signal transfer from the rod photoreceptor to the bipolar cell. This leads to parameter-free predictions of the bipolar cell response, which are in excellent agreement with experiments comparing rod and bipolar cell dynamics in the same retina. As far as we know this is the first case in which the computationally significant dynamics of a neuron could be predicted rather than modeled.     

A cytochemical and ultrastructural study of the “S.I.F.” cells in cat sympathetic ganglia

Summary According to the hypothesis of Eccles and Libet, the small intensely fluorescent cells (S.I.F. cells) in the sympathetic ganglion would represent an essential element in the inhibition of the principal neuron. As a contribution to the study of this important problem, we have investigated serial sections in superior cervical (S.C.G.) and celiac (C.G.) ganglia of the cat, a species that has not been extensively studied up to now, both by fluorescence and electron microscopy. We have shown that the S.I.F. cells are three times fewer in the cat S.C.G. than in the rat S.C.G. There are five times more S.I.F. cells in the C.G. of the cat than in the S.C.G. of the same species. Moreover we have described two types of S.I.F. cells.Type I is composed of cells characterized by highly polymorphous large dense-cored vesicles. These cells lack processes and are grouped in clusters centered on fenestrated capillaries. They could be endocrine function cells. Type II is formed of isolated cells which exibit long processes and establish synaptic junctions with the dendrites of the principal neurons. In this case, the dense-cored vesicles are very regular and much smaller. These cells could be equivalent to interneurons. Type I very strongly predominates in the S.C.G. and C.G. of the cat where it represents more than 90% of the S.I.F. cell total observed by fluorescence microscopy. A priori such a quantitative and qualitative heterogeneity hardly consistent with Eccles and Libet's hypothesis based on the existence of dopaminergic interneurons only, allows the question to be raised as to the functional significance of the S.I.F. cells in ganglion physiology. The notion of modulation of ganglionic transmission does not seem to be quiered by these new data but could be founded on different forms of action embodied in the broader conception of the neuromodulation phenomenon.     

Loss of heterozygosity in somatic cells of the mouse. An important step in cancer initiation?

Loss of heterozygosity (LOH) of tumour suppressor genes is a crucial step in the development of sporadic and hereditary cancer. Recently, we and others have developed mouse models in which the frequency and nature of LOH events at an autosomal locus can be elucidated in genetically stable normal somatic cells. In this paper, an overview is presented of recent studies in LOH-detecting mouse models. Molecular mechanisms that lead to LOH and the effects of genetic and environmental variables are discussed. The general finding that LOH of a marker gene occurs frequently in somatic cells of the mouse without deleterious effects on cell viability, suggests that also tumour suppressor genes are lost in similar frequencies. LOH of tumour suppressor genes may thus be an initiating event in cancer development.