Cytostatic effect of immune system cells on tumor cells

The cytostatic effect of different lymphoid cells on tumour cells was studied in mice. It was shown that the cells differed in their ability to manifest cytostatic and natural cytotoxic activity. The interstrain variations of cytostatic activity levels in murine splenocytes were revealed. The degree of cytostatic action of effector cells on tumour cells depended both on effector-target cells ratio and on the incubation time of effector and target cells. The cytostatic effect of splenocytes and macrophages was demonstrated to be unrestricted by H-2 complex and independent of the tumour type. The data suggest that the cytostatic effector cells are heterogeneous and may be distinct from natural killer cells.     

Maintenance of adult hamster pancreas cells on fibroblastic cells

Summary The maintenance of primary cultures of adult hamster pancreatic cells on layers of irradiated C3H/10T1/2 cells was studied. Various types of pancreatic cells, acinar, islet and ductular cells could be identified in the cultures by light and electron microscopy. Morphologically the various pancreatic cells retained many differentiated characteristics of their respective in vivo cell types. Insulin production was maintained at near Day 1 levels for the 16 d in culture for which it was measured. Colonies of epithelial cells continued to grow during a 20 d culture period. It is believed that this procedure for maintaining functional and growing pancreas cells in culture may be a useful in vitro model for studying the initiation of pancreatic carcinogenesis. Supported by Grant R01 CA 20022 and Contract N01 CP33278 from the National Cancer Institute, National Institutes of Health, Bethesda, Maryland.     

C-type lectin receptors on dendritic cells and Langerhans cells

Dendritic cells and Langerhans cells are specialized for the recognition of pathogens and have a pivotal role in the control of immunity. As guardians of the immune system, they are present in essentially every organ and tissue, where they operate at the interface of innate and acquired immunity. Recently, several C-type lectin and lectin-like receptors have been characterized that are expressed abundantly on the surface of these professional antigen-presenting cells. It is now becoming clear that lectin receptors not only serve as antigen receptors but also regulate the migration of dendritic cells and their interaction with lymphocytes.     

Stem cells on patrol

Hematopoietic stem cells (HSCs) exist in the bone marrow and circulate in the blood. In this issue, Massberg et al. (2007) report that HSCs also travel through the lymphatic system. Furthermore, migration of HSCs--which express Toll-like receptors--allows the recognition of pathogenic molecules in peripheral tissues thereby promoting the local generation of innate immune cells at the site of infection.     

Carbohydrate antigens expressed on stem cells and early embryonic cells

Lewis X antigen (Le(X)) is a marker of embryonic stem cells, embryonal carcinoma cells and multipotential cells of early embryos in the mouse. Le(X) is carried by branched, high-molecular weight poly-N-acetyllactosamines (embryoglycan). While embryoglycan is present in human embryonal carcinoma cells, Le(X) is not expressed in human embryonic stem cells, embryonal carcinoma cells or inner cell mass cells. Instead, these cells express SSEA-3 and SSEA-4, both of which are carried by globo-series glycolipids. Le(X) is a marker of primordial germ cells or multipotential stem cells derived from primordial germ cells both in the mouse and human. In other species of vertebrates, Le(X) is widely expressed in early embryonic cells and primordial germ cells, but the mode of expression is not completely conserved among species. Le(X) is expressed in neural stem cells from both humans and mice. Hematopoietic stem cells are not reported to express the above carbohydrate markers. A marker of these cells is CD34, a membrane-bound sialomucin. Another sialomucin, CD164 (MGC-24v) is expressed in hemotopoietic progenitor cells. As a function of Le(X) in stem cells, the promotion of integrin action is proposed, based on analyses of glycoproteins with the marker, cDNA transfection experiments and the inhibitory effects of an anti-Le(X) antibody. Most probably, Le(X) antigen as well as poly-N-acetyllactosamines play roles in the interactions on the same membrane. On the other hand, O-linked oligosaccharides on CD34 and CD164 are probably involved in the regulation of cell adhesion and proliferation via intercellular recognition.     

Cytotoxic action of natural killer cells on human tumor cells

Natural killer cell cytotoxicity was studied in a 18-hour 51Cr-release assay in the cultures of human tumor target cells: K562 leukemia and lung adenocarcinoma (LAC) cells. The mean cytotoxic value was similar for K562 and LAC cells: 36.13 +/- 3.23% and 40.78 +/- 3.43%, respectively, although significant individual variability was recorded. The similar cytolytic action of blood mononuclear cells (MNC) on the two tumor lines was observed in 30% of normal donors. MNC from 30% donors produced more pronounced lytic action on K562 cells while MNC from other 30% donors lysed mainly LAC cells. In the competitive inhibition test cold K562 cells more effectively than cold LAC cells suppressed the MNC-induced lysis of both K562 and LAC cells.     

Effect of astroglial cells on hypoxia-induced permeability in PBMEC cells

An in vitro model of the blood-brain barrier (BBB),consisting of porcine brain-derived microvascular endothelial cells(PBMEC), was used to evaluate the effect of astrocytes in theBBB disruption during hypoxia. Hypoxia-induced hyperpermeability wasdecreased significantly in a coculture model of astroglia cells, either astrocytes or C6 glioma cells, with PBMEC and, to the same extent, whenglia cell-conditioned medium was used. Corresponding to effects onhypoxia-induced hyperpermeability, astrocyte- and C6 cell-conditioned medium diminished hypoxia-induced vascular endothelial growth factor(VEGF) mRNA and protein expression, which recently was shown to beresponsible for hypoxia-induced permeability changes in vitro. Theeffect on hypoxia-induced hyperpermeability and VEGF expression wasspecific for astroglia cells because conditioned medium from bovinesmooth muscle cells (BSMC) did not show any effect. Immunocytochemistryrevealed that 24 h of hypoxia disrupted the continuity of thetight junction protein, zonula occludens-1 (ZO-1), which lines thecytoplasmic face of intact tight junctions. These changes wereprevented when hypoxia was performed in glia cell-conditioned medium.Results suggest that astrocytes protect the BBB from hypoxia-inducedparacellular permeability changes by decreasing hypoxia-induced VEGFexpression in microvascular endothelial cells.

     

Inflammatory cells of teleostean fish: a review focusing on mast cells/eosinophilic granule cells and rodlet cells

In contrast to the roles played by monocytes/macrophages, neutrophils and lymphocytes, the presence and functions of basophils, mast cells/eosinophilic granule cells, eosinophils and rodlet cells in teleosts are areas of controversy. The tissue distribution of mast cells/eosinophilic granule cells in species from a certain genus shows a characteristic pattern, and this pattern is usually also present at the family level. Functionally, the mast cells/eosinophilic granule cells of teleosts show close similarity to the mast cells of mammals. Acute tissue damage is causing mast cell/eosinophilic granule cell degranulation and release of mediators of inflammation, whereas an increase in the number of these cells is often found in chronically inflamed tissues. The mast cells/eosinophilic granule cells of teleosts show marked diversity in their staining properties, with both basophilic and acidophilic components in their granules. In some fish families, e.g. the labrids, the eosinophilic component is dominating, whereas in the pike the granules are strongly basophilic and show the metachromatic staining characteristics found in the granules of mast cells, but being more akin to the granules of the mucosal than to those of the connective tissue type of mast cells of mammals. With respect to rodlet cells, a cell type hitherto clearly demonstrated only in teleosts, a characteristic distribution pattern seems to be established in certain families. In other families rodlet cells are absent in some individuals and present in different tissues in others. However, there is a close relation between the presence of helminths or other noxious agents and the presence of rodlet cells. Massive aggregations of such cells can be seen in affected epithelia of gills or the intestinal tract, and in individuals of species from some fish families they also occur in association with mesothelial and endothelial tissues. The rodlet cell may represent a type of eosinophilic granulocyte that populates the tissues at its immature stage and mature in response to the appropriate stimuli, in a way similar to that of mast cell precursors. Present evidence points to a functional role for the rodlet cells of teleosts in host defence against parasites.     

Oestrogen action on bone cells

Sex steroids have an important impact on bone physiology. Oestrogen (E) appears to be the most important sex steroid in preventing osteoporosis in women. Despite the overwhelming evidence that oestrogens modulate bone growth and turnover in vivo, oestrogen receptors (ER) were detected only recently. Two forms of ER have been discovered so far, ERalpha and ERbeta. Both have been detected in osteoblasts and osteoclasts as well. A number of growth factors and cytokines appear to modulate bone resorption in vitro and in vivo. Among others, interleukin-1 and -6 and tumor necrosis factor alpha and beta were found to be extremely potent stimulators of bone resorption. Binding of different cytokines to their receptors in osteoblasts result in the release of soluble factors that act directly on osteoclasts to modulate their recruitment or activity. Thus, E, apart from the direct regulation of osteoclasts, which it achieves through its receptors, can inhibit the release of osteoclast stimulatory factors or enhance the release of osteoclast inhibitory factors. In general, E is an inhibitor of bone resorption that decreases both osteoclast numbers and activity. Recently, it has also been shown that it promotes apoptosis. Moreover, it also has anabolic effects on osteoblasts. However, E action on osteoclasts is superior in comparison with that on osteoblasts. Recent data have shown that transforming growth factor beta (TGFbeta) mediates the actions of E in bone. Following the example of raloxifene it may be proved that the role of TGFbeta in the actions of E in bone is central and has not only academic interest. More data are needed to elucidate this issue. Finally, recent data suggest the importance of E for bone maturation and development of peak bone mass in men. It seems likely that both E and androgens are required for the growth and maintenance of the adult male skeleton.     

Studies on low-level MDR cells

Acquired or spontaneous resistance is a major clinical problem in the treatment of cancer. Low levels of MDR gene expression or P-glycoprotein have been correlated with a high level of drug resistance in vitro and a poor response to chemotherapy in some tumors. A strong correlation between MDR mRNA, P-glycoprotein levels and degree of drug resistance has not been found in several resistant model tumor cell lines. In some cell lines at low and high level of resistance different mechanisms seem to be involved.     

l-tyrosine-binding proteins on melanoma cells

Summary Crosslinking of [¹⁴C]l-tyrosine to at least five hamster melanoma cell surface proteins is reported. This effect was abolished by addition of nonradioactivel-tyrosine,l-phenylalanine, orl-dopa, but not byd-tyrosine, tyramine, dopamine, norepinephrine, or epinephrine. The above proteins can be purified by tyrosine-affinity chromatography. They have molecular weights different from proteins staining for dopa oxidase and proteins that bind anti-tyrosinase antibody in Western blots. It is suggested that they may be a hithergo unrecognized part of the cellular apparatus governing melanogenesis.