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PubMed1982

The morphometric composition of myelinated fibres by nerve, level and species related to nerve microenvironment and ischaemia.

An extensive morphometric evaluation of the number, density and diameter distribution of myelinated fibres (MFs) of different nerves, of different proximal-distal levels of nerves, and of different species is reported. The methodology used provides reliable estimates of number and size because of the use of optimal histological techniques, semi-thin sections, careful systematic sampling, nonsubjective evaluation of transverse MF profiles using computerized imaging and evaluation of large numbers of MFs and nerves. The non-MF percentage of endoneurial area was also measured as an index of the amount of nerve microenvironment. We have confirmed that the MF composition is quite variable between nerves, between levels of nerves, and between species. In general the density of MFs is lower in the nerves of man than in the nerves of other animals evaluated, in distal than in proximal levels, in old age and in disease. Although increased endoneurial fluid may play a role in resistance to ischaemic block it appears that the intrinsic metabolic properties of the neural tissue itself are most important.

Animals↗
PubMed1981

[Transfer of bone marrow microenvironment by stromal cells grown in culture and transplanted into sponges].

Monocellular suspensions from trypsinized CBA mouse bone marrow cells were explanted to monolayer cultures. The cells of the adhesive layer withdrawn from 15-30-day cultures were transplanted in gelatin sponges beneath the kidney capsule from syngeneic recipients. The transplantation was accompanied by bone formation and by transfer of bone marrow microenvironment in the overwhelming majority of cases.

Animals↗
PubMed1981

The human thymus microenvironment: in vivo identification of thymic nurse cells and other antigenically-distinct subpopulations of epithelial cells.

We have studied the human thymus microenvironment in order to identify subsets of cells that may be responsible for the induction of different aspects of T-lymphocyte differentiation, education and MHC restriction. Using immunofluorescence on tissue sections and cell suspensions we have found MHC products (HLA-A, B, C and DR) to be present throughout the thymus epithelium whilst human T-cell antigens are absent from all non-lymphoid cells. In contrast, Thy-1 antigen (expressed on approximately 1% paediatric human thymocytes) has a differential expression amongst thymic epithelial cells, being confined to those in the subcapsular cortex and to 'thymic nurse cells' (TNC). The former represent the site to which thymocyte precursors first migrate upon entering the thymus. The latter are large epithelial cells, located within the cortex, whose plasma membrane totally enclose a number of thymus lymphocytes; these cells are therefore good candidates for the mediators of direct contact (stromal) induced thymocyte maturation.

Antigens↗
PubMed1982

Effects of chloramphenicol on hematopoietic inductive microenvironment.

Effects of chloramphenicol (CP) on hematopoietic inductive microenvironment (HIM) were studied using in vitro and in vivo assay systems. HIM was represented as fibroblast colonies (CFUF) in in vitro culture. CP suppressed the growth of not only granuloid committed progenitor cells (CFUC), but also CFUF in in vitro culture at the concentration of 10, 50 and 100 micrograms/ml. To analyze the function of HIM in vivo, the subcutaneous bone implantation method was used. The recovery of hematopoietic stem cells in subcutaneously implanted femora of mice, which were treated with a 500 mg/kg dose of CP daily for 6 days, was significantly decreased compared to the sham treated group. Suppressive effect of CP on HIM was shown. The important role of the derangement of HIM on the pathogenesis of CP-induced aplastic anemia was discussed.

Anemia, Aplastic↗
PubMed1982

[Stromal bone marrow cells and the hematopoietic microenvironment].

Stromal clonogenic fibroblasts of the bone marrow possessing osteogenic potential are responsible for hemopoietic bone marrow microenvironment. These cells may be recovered from the bone marrow by cloning in cell cultures; their progeny cells upon retransplantation into the body form new bone marrow organs. Microenvironmental cells are histogenetically independent of hemopoietic cells. In bone marrow cell suspensions prepared by bone marrow tissues trypsinization stromal clonogenic cells are present in greater concentrations than in those prepared by mechanical mincing of the bone marrow tissue. New ectopic bone marrow organs may be created by transplantation of trypsinized suspensions in porous sponges.

Animals↗
PubMed1980

Effects of antibacterial microenvironment on in vitro plaque formation of Streptococcus mutans as observed by scanning electron microscopy.

This study presents in vitro techniques to follow the adsorption and subsequent surface proliferation of Streptococcus mutans on hydroxyapatite surfaces leading to artificial plaque. Inhibition of proliferation as well as extracellular dextrane formation can be achieved by pretreatments of the hydroxyapatite surface with aqueous solutions of sodium ricinoleate. The antibacterial activity is restricted to an antibacterial microenvironment adjacent to the hydroxyapatite surface.

Adsorption↗
PubMed1981

Influence of microenvironment and vascular anatomy on "metastatic" colonization potential of mammary tumors.

This communication reports experiments demonstrating that some sites in which tumor cells lodge reproducibly fail to support secondary colony formation by a particular tumor, even though cells from the same tumor are already proven to have high colonization potential in other organs. The effect is not an expression of nonspecific hostility to tumor growth, since cells from certain other tumors readily colonize the same site. Cell suspensions obtained by disaggregation of a series of naturally occurring murine mammary tumors were each inoculated by four different routes into separate batches of syngeneic animals, and the resulting degree and distribution of colonization were studied 90 days later at autopsy. Standard doses of 1 million viable tumor cells were injected either i.p. or s.c. into the tail vein or the hepatic portal vein. It was found that some tumors could reproducibly colonize by all routes, whereas others could colonize only by a few, and the combination of sites colonized varied from tumor to tumor; still others were unable to grow in any site. Cells from nonneoplastic lactating mammary glands did not establish any colonies. We have demonstrated previously that individual naturally occurring mammary tumors differ in their pulmonary colonization potentials after i.v. inoculation and that the potential of a given tumor is an intrinsic property of its constituent cells. The current findings are evidence that the microenvironment of an organ can inhibit or permit expression of this intrinsic potential and that the degree and sites of colonization are thus the results of interaction between tumor and organ-specific factors. It was also found that circulatory anatomy partially influenced the distribution of colonies and that colonization of distant organs after blood-borne dissemination is distinct from general tumor transplantability.

Animals↗
PubMed1981

Regeneration of hemopoietic precursor cells in spleen organ cultures from irradiated mice: influence of genotype of cells injected and of the spleen microenvironment.

The regeneration of hemopoietic precursor cells (colony-forming cells, CFC) was monitored in spleen organ cultures from lethally irradiated mice injected with 10(7) normal syngeneic or allogeneic bone marrow cells. The important role of the microenvironment in supporting hemopoiesis was confirmed by the failure of mutant S1/S1d spleens to support CFC regeneration in organ cultures. However, the extent and quality of the CFC regeneration was clearly dependent on the genetic properties of the injected cells. Evidence for this was obtained from the regeneration patterns of various CFC types in organ cultured spleens derived from different mouse donor-recipient strain combinations (CBA/CBA, CBA/C57BL, CBA/BALB/c, C57BL/C57BL, C57BL/CBA, C57BL/BALB/c) that maintained the differences in the bone marrow frequency of various CFC types characteristic of the donor strain.

Animals↗
PubMed1980

Studies of the haemopoietic microenvironments. III. Glycosaminoglycan levels in relation to phenylhydrazine-induced erythropoiesis in the mouse liver.

The possible relation between haemopoietic activity and glycosaminoglycan levels in the haemopoietic microenvironment was examined in ectopic erythropoiesis, induced by phenylhydrazine treatment, in the liver of adult mice. The hepatic glycosaminoglycan content in the liver was determined biochemically over a period of 9 d following induction of haemolytic anaemia. After induction sulphated glycosaminoglycan levels increased up to d 4, then decreased to subnormal levels on d 5 and returned to normal values on the following days. The pattern of changes in GAG content coincided with changes in the number of CFU-S and with the number of erythroblasts in the liver. This observation fits in with the hypothesis of McCuskey et al (1972) stating that high sulphated glycosaminoglycan levels are favourable for stem cell proliferation, whereas low sulphated glycosaminoglycan levels favour erythropoiesis.

Anemia, Hemolytic↗
PubMed1994

Development of the chick thymus microenvironment: a study by lectin histochemistry.

The microenvironment of the chick thymus has been examined during development using lectin histochemistry. We have assayed WGA, Con A, RCA-I and TPA on thymic sections from 13, 15, 17 and 19 d chick embryos and 0, 5, 10 and 15 d chicks. All lectins were immunoperoxidase and colloidal gold-conjugated for transmission electron microscope observations. WGA labelled both the cortical and medullary thymic stroma at all the stages analysed. An intense reaction to WGA was observed in the subcortical region from stage 18 embryos to 5 d chicks. On the other hand, WGA did not stain medullary areas of the chick thymus. Con A lectin detected several cell clusters of stromal cells and thymocytes in cortical regions. These clusters could represent a lymphostromal complex with which Con A receptors are associated, probably in relation to cell adhesion. The residues detected by RCA were distributed both in stromal cells and thymocytes of the developing chick thymus. There was an increase of the reaction to RCA between the 19 d embryos and the 5 d chicks. This increase might be interpreted in terms of the secretion of thymic humoral factors at these stages. The thymic stromal cells stained with immunoperoxidase conjugated-TPA showed a reticular pattern in the medulla. There is a possibility that the fucosyl residues may be expressed in the Ia antigen as has previously been suggested in other species.

Animals↗
PubMed1995

The relevance of cell microenvironments for the appearance of lympho-haemopoietic tissues in primitive vertebrates.

In higher vertebrates, mainly in mammals, a role for the non-lymphoid components of lymphoid organs in governing the maturation and functioning of immune system has been largely demonstrated. In contrast, such a role in the evolution of the vertebrate immune system has only been evidenced indirectly. In the present review we summarize histophysiological results which emphasize the relevance of lympho-haemopoietic stromal elements in the emergence and evolution of vertebrate lymphoid organs. The most primitive vertebrates, the Agnatha, have no true lymphoid organs and, accordingly, their immune responses seem more related to the non-anticipatory defence mechanisms of invertebrates than to the immune responses of vertebrates. So, the appearance and evolution of vertebrate lymphoid organs seems closely related with the emergence of immune capacities. Thymus, spleen and gut-associated lymphoid organs appear early in phylogeny whereas lymph nodes and bone marrow are late phylogenetical adquisitions. However, bone marrowless vertebrates contain numerous organs (i.e., gonads, kidney, brain, etc...), the cell microenvironments of which support lympho-haemopoiesis mimicking the condition of higher vertebrate bone marrow. On the other hand, the lack of germinal centres, another feature of the lymphoid organs of ectothermic vertebrates which impedes the selection of B cells raised after somatic hypermutation, presumably reflects the absence of some of the elements necessary for this organization.

Animals↗
PubMed1993

Mast cells and their microenvironment: the influence of fibronectin and fibroblasts on the functional repertoire of rat basophilic leukemia cells.

To determine how the microenvironment in which mast cells are located may influence their function, we explored the effects of fibronectin and fibroblasts on histamine secretion in vitro from a mast cell model, the rat basophilic leukemia (RBL-2H3) cell line. RBL-2H3 cells bound specifically to fibronectin-coated surfaces. Binding was maximal by 1 hour, was not detectable at 0 degrees C or in the absence of Ca++, and was inhibited by preincubating the cells with a synthetic peptide containing the RGD sequence. Adherence to fibronectin stimulated RBL-2H3 cell spreading with a concomitant reorganization of the cytoskeleton and a repositioning of the cytoplasmic granules to the cell periphery. Although adherence to fibronectin did not by itself induce histamine release, when stimulated by either immunologic or non-immunologic means, fibronectin-adherent cells released dramatically more histamine than cells plated in wells coated with BSA only. Thus, RBL-2H3 cells bind specifically to fibronectin, and in so doing are stimulated to undergo changes in morphology and enhanced responsiveness to secretory stimuli. RBL-2H3 cells grown in coculture with 3T3 fibroblasts, but not RBL-2H3 cells grown alone, became responsive to the polymeric synthetic secretagogue Compound 48/80 and the neuropeptide Substance P. Maximum sensitivity to Compound 48/80 was attained by the second week in coculture. Histamine release was dose-dependent, noncytotoxic and occurred even in the absence of extracellular Ca++. Contact between the 2 cell types appeared to be a critical factor. RBL-2H3 cells, separated from 3T3 cells by a 0.45 micron filter, failed to secrete histamine in response to Compound 48/80.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Development of lymphopoiesis as a function of the thymic microenvironment. Use of CD8+ cytotoxic T lymphocytes for cellular immunotherapy of human cancer.

The mammalian thymic histogenesis can be immunomorphological divided into three consecutive states: 1) Epithelial: 2) Lymphopoietic or lympho-epithelial and 3) Differentiated cellular microenvironment with formation of Hassall's bodies. The embryonic, epithelial pharynx serves as the origin of the mammalian thymus. The epithelial cell layer of endodermic origin expands into pharyngeal pouches and the thymic anlagen are formed from the dorsolateral portions of the third pharyngeal pouch. In absence of humoral and cell to cell interactions with the ectomesenchyme, the primary epithelial anlagen are unable to proliferate. Experimental or spontaneous neural crest ablation early in ontogenesis also results in non-physiologic thymic organogenesis. Earlier thymic studies detected a subcapsular A2B5+ and Thy-11+, TE4+, Vimentin+, Cytokeratin+ endocrine reticulo-epithelial cell or nurse cell subpopulation within the cortical reticulo-epithelial cell network. Secretion of multiple in situ active, autocrine growth factors and a humoral chemotactic factor by the cells of ectomesenchymal origin allows the commencement of immigration of hemopoietic stem cells. The thymic lymphopoiesis is initiated by the immigration of pluripotent (with cellular immunophenotype TdT+, Ki67+, CD3-, CD7+, CD34+, CD38+, CD44+, CD45+ or T200+), but already to T lymphocyte cell lineage committed hemopoietic stem cells during the 6-7th week of ontogenesis. CD2, a 50-55 kD glycoprotein is the first intrathymic, early differentiation antigen expressed during the 8-9th ontogenetic weeks. This antigen also serves as a cell surface component of the alternative or antigen independent pathway of thymocyte activation. The 10th week is defined as the first expression of CD4 and CD8 antigens which determine the basic, characteristic dichotomy of the T lymphocytes. The induction of the initial proliferative wave of immature cortical thymocytes is carried out by the LFA-3 (CD58) adherence molecules, the receptors of CD2 antigens located on reticulo-epithelial cells. As a result of the extremely high proliferation rate the thymic mass markedly expands in all dimensions and numerous microlobules are formed. Between the 13th to 16th week the typical thymic cell environment is formed and the first Hassall's bodies are developed. The outer layer of the bodies contain hypertrophized TE8+, TE16+ and TE19+ reticulo-epithelial cells, with an active secreting cytoplasmic structure. Cytotoxic cells express special receptors by which they are capable to distinguish altered or foreign cells from autologous cells of the host. Solid human tumors are characterized with a marked poly- and mononuclear cell infiltrate containing phagocytes, various subtypes and clones of lymphocytes and granulocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

[The morphofunctional heterogeneity between peritoneal and alveolar macrophages in their biogenic amine content: the effect of their presence or absence in the microenvironment of mast cells].

Peritoneal macrophages differ from alveolar ones in biogenic amine content: peritoneal macrophages contain smaller amounts of histamine and serotonin. When activated, alveolar macrophages release biogenic amines, whereas in peritoneal macrophages stimulators of macrophage activity induce the increase in amine content. This may be due to the presence of mast cells in their microenvironment macrophage activity.

Animals↗
PubMed1994

Ultrastructural study of the hemopoietic microenvironment in human fetal spleen.

Reciprocal interactions between hemopoietic stromal cells and immature hemopoietic cells in human spleens obtained from 20 fetuses of 10-28 weeks gestation were observed by transmission electron microscopy and scanning electron microscopy. The close association of stromal cells with immature hemopoietic cells was confirmed under the electron microscope and a presumptive HIM (Hemopoietic inductive microenvironment) was visualized. In regions of immature hemopoietic cell-reticular cell, endothelial cell, macrophage and interdigitating cell contact, some communicating structures were found between the plasma membranes of adjacent cells; moreover, the cytoplasm of these four stromal cells were full of various kinds of organelles. These results suggest that reticular cells, endothelial cells, macrophages and interdigitating cells are component parts of the HIM of human fetal spleen and that these cells have a nurturing function in relation to hemopoietic cells.

Animals↗
PubMed1993

Adherence of normal and neoplastic human B cell precursors to the bone marrow microenvironment.

The early development of B lineage cells occurs in the bone marrow in close association with fibroblast-like accessory cells. The integrin VLA-4 is preferentially expressed by B cell precursors and mediates adhesion of B cell precursors to bone marrow derived fibroblasts (BM-FB), which express a VLA-4 counter/receptor, VCAM-1. The functional importance of this adhesion interaction is suggested by the inhibition by anti-VLA-4 antibody of in vitro proliferation of B cell progenitor colonies grown with a BM-FB adherent layer. In order to compare adhesion requirements of normal versus neoplastic human B cell precursors, quantitative expression of adhesion proteins by primary human B cell precursor acute lymphoblastic leukemia (BCP-ALL) cells was studied by flow cytometry. BCP-ALL cells expressed VLA-4 and VLA-5 at similar levels as normal immature B cell precursors. However, other adhesion molecules, particularly CD44, were overexpressed by the leukemic cells relative to their normal counterparts. Similar to normal B cell precursors, adhesion of BCP-ALL cells to BM-FB was inhibited by antibodies to VLA-4 and VCAM-1. These results suggest that the ordered program of adhesion protein expression and functional activation during B cell development is at least partially intact in BCP-ALL cells, and may play a role in tissue localization and growth of the neoplastic cells. The focal pattern of spreading of adherent BCP-ALL cell lines on individual cells in the BM-FB adherent layer suggests functional heterogeneity in the bone marrow microenvironment that may be essential in regulating normal and neoplastic lymphopoiesis.

Antigens, CD↗
PubMed1994

Quality and functional capacity of the bone marrow microenvironment of autologous blood stem cell transplantation (ABSCT) recipients.

We have previously reported that the rate of haematopoietic recovery following Autologous Blood Stem Cell Transplantation (ABSCT) could be influenced by the type of conditioning regimen or by the underlying disease. Furthermore, Peripheral Blood Stem Cell (PBSC) growth was found to be sensitive to stimulation by irradiated allogeneic stromal layers. In the present study, we used the long term culture system (LTC) to investigate the quality of the bone marrow (BM) microenvironment from patients who had undergone ABSCT for either Malignant Lymphoma (ML, 13 patients) or Multiple Myeloma (MM, 8 patients) after conditioning regimens comporting myeloablative chemotherapy (CT) or Total Body Irradiation (TBI). Among the 13 ML patients, 10 received CT conditioning and 9 of the 10 BM samples developed a complete confluent stromal layer. The remaining 3 ML patients received TBI prior to ABSCT and 2 of the 3 samples developed confluent stroma. In contrast, when LTC were established with BM from the 8 MM patients, all of whom were treated with TBI prior to ABSCT, only 3 of the 8 marrow samples developed a complete confluent stromal layer. Thus BM from patients who had received CT conditioning therapy tended to form confluent stroma more often than BM from those who had received TBI (p = 0.08). CFU-GM production was also evaluated for the stromal layers derived from all transplanted patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow↗
PubMed1994

Appearance of homogeneous smectic multilamellar microenvironments in biomembranes undergoing superoxide-initiated lipid peroxidation: lipid-dienyl radical accumulation and fluidity management in lipid bilayers.

Erythrocyte ghosts were exposed to various levels of oxyradical shock in order to identify the extent of accumulation of peroxidative intermediates. Malondialdehyde reacting end products were the same in all different models. But, the accumulation of dienyl radical species increased with higher intensity of oxyradical shock. These dienyl radicals may rearrange to create a homogeneous smectic multilamellar microenvironment which may be more fluid in terms of the molecular dynamics.

Erythrocyte Membrane↗