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At least 1,459 records · Page 81Linked to original sources
PubMed1986

Fluorescence probe measurement of the pH of the transferrin microenvironment during iron uptake by rat bone marrow erythroid cells.

Fluorescence probe measurements of the transferrin micro-environment during iron uptake by rat erythroid cells revealed that part of the transferrin is taken up in an acidic environment. The pH of this intracellular transferrin environment is 5.7. When rat erythroid cell precursors are incubated with diferric transferrin then in the incubation medium monoferric transferrins TfNFe and TfFeC appear. In view of the known instability of TfNFe at acidic pH, TfNFe cannot arise after endocytosis of Tf2Fe in acid vesicles at pH below 6.0. The results support the existence of a mechanism other than endocytosis in the iron uptake process in rat erythroid cells.

Animals↗
PubMed1995

Chimaeric cultures of human marrow stroma and murine leukaemia cells: evidence for abnormalities in the haemopoietic microenvironment in myeloid malignancies and other infiltrating marrow disorders.

PGM-1 is a transplantable C3H/HeJ leukaemia which is not viable in unstimulated in vitro culture, differentiates into mature granulocytes and macrophages in response to soluble cytokines, and undergoes self-renewing cell divisions in coculture with selected human bone marrow stromal cell lines. When PGM-1 cells were cultured on pre-established adherent layers from primary human marrow samples, their fate depended on the source of the human marrow. Adherent layers from healthy marrow donors or patients with reactive marrow alterations had no or very little capacity to maintain PGM-1 cells in an immature colony-forming state. However, in coculture with adherent layers from patients with myeloid leukaemia or, to a lesser extent, lymphoblastic leukaemia or marrow-infiltrating lymphoma the colony-forming potential was retained. There was no correlation between the remission status of the patient and the PGM-1 activity of the adherent layer. Consistent morphological differences between active and inactive stromal layers were not observed. The PGM-1 coculture system enables the detection of a hitherto undescribed regulatory abnormality in bone marrow malignancies. Whether the PGM-1 supporting activity is mediated through differences in the production of a cytokine with close homology to complement factor Bb which has recently been shown to induce self-renewal in immature PGM-1 cells, requires further investigation.

Animals↗
PubMed2006

Differential gene expression in non-malignant tumour microenvironment is associated with outcome in follicular lymphoma patients treated with rituximab and CHOP.

Rituximab in combination with chemotherapy (immunochemotherapy) is one of the most effective treatments available for follicular lymphoma (FL). This study aimed to determine whether differences in gene expression in FL tissue correlate with outcome in response to rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy (R-CHOP). We divided 24 patients into long- [time to treatment failure (TTF) >35 months] and short-term (TTF <23 months) responders, and analysed the gene expression profiles of lymphoma tissue using oligonucleotide microarrays. We used a supervised learning technique to identify genes correlating with outcome, and confirmed the expression of selected genes with quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Among the transcripts with a high correlation between microarray and qPCR analyses, we identified EPHA1, a tyrosine kinase involved in transepithelial migration, SMAD1, a transcription factor and a mediator of bone morphogenetic protein and transforming growth factor-beta signalling, and MARCO, a scavenger receptor on macrophages. According to Kaplan-Meier estimates, high EPHA1, and low SMAD1 and MARCO expression were associated with better progression-free survival (PFS). Immunohistochemistry showed that EphA1 was primarily localised in granulocytes. In addition, both EphA1 and Smad1 were expressed in vascular endothelia. However, no difference in vasculature was detected between long- and short-term responders. In a validation set of 40 patients, a trend towards a better PFS was observed among patients with high EphA1 expression. We conclude that gene expression in non-malignant cells contributes to clinical outcome in R-CHOP-treated FL patients.

Adult↗
PubMed2004

Influence of tissue origins and external microenvironment on porcine foetal fibroblast growth, proliferative life span and genome stability.

One of the challenges of manipulating genes in primary cells is that the cells have a finite proliferation capacity. This, combined with the lower gene targeting efficiency of somatic cells, makes identification of targeted clones very difficult. The objective of this study was to establish a system that allows porcine foetal fibroblasts to reach their maximal proliferation capacity in vitro. The influence of fibroblast origin, stage of foetal development, cell seeding densities and concentration of foetal bovine serum (FBS) on the population doublings, the percentage of beta-galactosidase-activity-positive cells and the genome stability of foetal fibroblasts during in vitro culture was investigated. It was found that porcine foetal fibroblasts could be cultured for over 80 population doublings in the appropriate culture system. Fibroblasts from earlier stages of foetal development were better candidate cells than those from the later stages. Cells from the heart were more actively proliferative and more resistant to replicative senescence than those from the liver. Compared to 10% FBS content, 15% FBS provided better homeostatic support, not only to proliferative performance, but also in maintaining a normal karyotype. In addition, the proliferative life span of porcine foetal fibroblasts is also dependent on seeding density of the culture.

Animals↗
PubMed1994

Functional heterogeneity of mast cells isolated from different microenvironments within nasal polyp tissue.

Nasal polyposis is a chronic inflammatory condition of the upper airways characterized by infiltration of activated inflammatory cells, including mast cells, both in the epithelium and in the stroma. The aim of this work was to study human mast cells derived from two different anatomical sites within the same nasal polyp tissue. To this end, we isolated two distinct mast cell populations, one from the epithelial and the other from the stromal layers of individual human nasal polyp tissues. We examined the mediator content of the two mast cell populations and found that stromal mast cells had a significantly higher content of tryptase compared with the epithelial mast cells from the same tissue. In addition, mast cells from the stromal compartment, but not those from the epithelium, released a significant amount of histamine after anti-IgE stimulation. By contrast, both populations released over 50% of the total histamine after non-specific stimuli (A23187 10(-6) M). The content of mediators and the response to immunological activation were not significantly altered in patients receiving topical steroid therapy. It remains to be determined if the observed differences are the result of an intrinsic characteristic of the mast cell populations localized to separate tissue compartments, or reflect a different in vivo exposure to stimuli such as antigens, or different surrounding structural or infiltrating cells. In conclusion, these data provide evidence of functional heterogeneity and differences in mediator content between mast cell subpopulations from a single human tissue. The failure of release of epithelial mast cell mediators from an immunologic stimulus may have implications concerning acute effects of antigen exposure in nasal polyposis.

Adult↗
PubMed2004

The lung cytokine microenvironment influences molecular events in the lymph nodes during Th1 and Th2 respiratory mucosal sensitization to antigen in vivo.

Originally defined by their patterns of cytokine production, Th1 and Th2 cells have been described more recently to express other genes differentially as well, at least in vitro. In this study we compared the expression of Th1- and Th2-associated genes directly during in vivo sensitization to ovalbumin (OVA) in Th1- and Th2-polarized models of airways inflammation. Th1-polarized airway inflammation was achieved by the intranasal instillation of adenoviral vectors (Ad) encoding granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-12, followed by daily aerosolizations of OVA; instillation of Ad/GM-CSF alone with OVA aerosolization led to Th2-polarized responses. Lymph nodes were obtained at various time-points, RNA extracted, and analysed by real-time quantitative polymerase chain reaction (PCR). Consistent with reports from in vitro and human studies, mice undergoing Th1-polarized inflammation showed preferential expression of the transcription factor t-bet, the chemokines IFN-gamma inducible protein (IP)-10 and macrophage inflammatory protein 1 alpha (MIP-1-alpha), and the chemokine receptor CCR5. In contrast, the transcription factor GATA-3, the chemokines I-309 and thymus and activation regulated chemokine (TARC), and the chemokine receptors CCR3 and CCR4 were preferentially expressed in the Th2 model. Importantly, we also show that Ad/transgene expression remains compartmentalized to the lung after intranasal instillation. Flow cytometric analysis of lung myeloid dendritic cells indicated that B7.1 was expressed more strongly in the Th1 model than in the Th2 model. These studies provide a direct comparison of gene expression in in vivo Th1- and Th2-polarized models, and demonstrate that molecular events in the lymph nodes can be altered fundamentally by cytokine expression at distant mucosal sites.

Animals↗
PubMed2005

In ovo vitelline duct ligation results in transient changes of bursal microenvironments.

The avian bursa of Fabricius has a direct connection to the cloaca via the bursal duct. Using the bursal duct ligation technique, it has been clearly shown that the B cells of the bursal follicles develop under the influence of cloacal antigens. These antigens have been suggested to be present on the bursal secretory dendritic cells in immunoglobulin G (IgG)-containing complexes. We studied the effect of maternal (yolk) antigens on the early development of B cells and the appearance of IgG-containing complexes of the bursal dendritic cells with a novel embryo manipulation technique, in ovo vitelline duct ligation. This operation blocked the direct (intestinal) transport of yolk substances into the intestine, but left the vitelline circulation intact. Vitelline duct ligation performed on embryonic day 17 resulted in serious but transient bursal underdevelopment during the first week of life: (1) IgG and the follicular dendritic cell marker 74.3 were not detectable on the bursal secretory dendritic cells, in spite of a normal serum IgG level and free communication with the cloacal lumen; (2) the number of B cells in the follicles was greatly reduced and they showed an altered phenotype, resembling that of the prebursal B cells. The intracloacal administration of different proteins effectively restored the bursal phenotype. These data suggest that maternal antigens indirectly help the maturation of bursal secretory dendritic cells and concomitantly that of B cells during the first week of life.

Animals↗
PubMed1979

Maturation of bursal stem cells within allogeneic or syngeneic bursal microenvironment: surface determinants and capacity for germinal centre formation.

Maturation of bursal stem cells in an allogeneic environment was studied. The occurrence of surface IgM, surface IgG, and Ia-like antigens on B cells after differentiatoin within an allogeneic bursa was studied. Furthermore, the immediate capacity of B cells to form germinal centres after differentiation in an allogeneic bursa was studied by injecting them with histocompatible T cells into "test-tube" birds. The results indicate that the switch to surface-IgG-bearing cells occurs in an allogeneic bursa in a similar manner as in a syngeneic bursa. Studies of the occurrence of Ia-like antigens on bursa cells demonstrate that they retain their original Ia-like antigens, even during maturation in an allogeneic host. Third, the results demonstrate that after differentiation within an allogeneic environment bursa cells have acquired the ijmediate capacity to cooperate with histocompatible T cells as measured by germinal centre formation in "test-tube" birds.

Animals↗
PubMed2006

Dendritic cells therapy confers a protective microenvironment in murine pregnancy.

The fetal-placental unit is a semi-allograft and immunological recognition of pregnancy, together with the subsequent response of the maternal immune system, is necessary for a successful pregnancy. Dendritic cells (DC) show a biological plasticity that confers them special characteristics regulating both immunity and tolerance. Therapy employing DC proved to diminish the abortion in the DBA/2J-mated CBA/J females; however, the underlying mechanisms remain unknown. Here, we evaluated whether DC therapy influences the presence of immunoregulatory populations of cells at the fetal-maternal interface. To address this hypothesis, we analysed the pregnancy-protective CD8, gammadelta cell populations as well as transforming growth factor (TGF)-beta1 and progesterone-induced blocking factor (PIBF) expression at the fetal-maternal interface from abortion-prone female mice that had previously received adoptive transfer of syngeneic DC. Syngeneic DC therapy induced an increase in the number of CD8 and gammadelta cells. Additionally, an upregulation of TGF-beta1 and PIBF expression could be detected after DC transfer. We suggest that DC therapy differentially upregulates a regulatory/protective population of cells at the fetal-maternal interface. It is reasonable to assure that this mechanism would be responsible for the lower abortion rate.

Abortion, Habitual↗
PubMed1988

N.m.r. analyses of the histidine microenvironments in a human salivary proline-rich glycoprotein.

The pKa's of the three histidine residues in a proline-rich glycoprotein from human parotid saliva (PRG) were determined by 360 MHz proton n.m.r. spectroscopy. The addition of calcium (0.64 mM) caused drops in the pKa's of all three histidines by approximately 0.25 units. When imidazole and cyclo)L-histidine-L-proline) were used as model compounds, corresponding concentrations of calcium had no effect on their pKa's. Also, the model compounds gave absolute pKa values in good agreement with similar chemical species reported in the literature. Exchange lifetime data and previously reported hydrogen----deuterium exchange experiments suggest that the PRG histidine N tau H protons are not involved in hydrogen-bonds. Collectively, these data imply that changes in PRG conformation occur upon the addition of calcium.

Amino Acid Sequence↗
PubMed1998

Blood cell precursors in context. Composition of the bone marrow microenvironment that supports B lymphopoiesis.

New molecular approaches are rapidly yielding information about the composition of bone marrow and culture studies suggest possible functions for many molecules in that organ. However, the marrow is extraordinarily complex with respect to interactions between cells and their behaviour may not be adequately modeled in culture. It is becoming apparent that post-translational modifications and function of proteins can be highly influenced by the cellular and extracellular environment. Therefore, in vivo studies will continue to be important for understanding this remarkable organ.

Apoptosis↗