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Results for “tissue microenvironment”

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PubMed2000

The role of B cells and autoantibodies in multiple sclerosis.

A variety of cellular and humoral immunological abnormalities have been observed in multiple sclerosis (MS). In the past few years, several lines of evidence converged to imply an important role of autoreactive antibodies and B cells in the pathogenesis of MS. Recent data suggest that autoantibodies may be harmful in lesion formation but also potentially beneficial in repair. This review surveys recent advances in the concepts of generation and nature of pathogenetic autoantibodies, their potential modes of action, mechanisms of their long-term persistence, and the role of the inflamed brain tissue as a B-cell-supporting microenvironment in MS. Based on the presence of specific autoantibodies, it seems possible to define distinct MS subgroups in the near future. The therapeutic relevance of these new findings is presented.

Animals↗

PubMed2000

Tolerance and immunity in the intestinal immune system.

The intestinal immune system must guard the body against invasion by pathogens while avoiding a response to the many potential antigens present in food. In the absence of the inflammatory stimuli necessary to elicit an immune response, oral administration of soluble protein antigens induces antigen-specific systemic nonresponsiveness. Recent studies have shown that peripheral nonresponsiveness to orally administered antigen is preceded by transient T-cell activation and is due primarily to the induction of functional T-cell anergy. The microenvironment of the gut-associated lymphoid tissue plays a central role in orally induced nonresponsiveness by supporting the growth of regulatory T cells that maintain intestinal homeostasis in the face of constant antigenic challenge. The transfer of nonresponsiveness by peripheral T cells from antigen-fed mice suggests that these-gut-derived regulatory cells also function in peripheral sites. When oral antigens are presented with adjuvants (microbial products that activate the innate immune system) an adaptive immune response is induced to this normally tolerogenic form of antigen. This review examines recent work that has provided new insight into the regulation of tolerance and immunity in the intestinal immune system.

Animals↗

PubMed1992

[Changes of microenvironment and tumor cell heterogeneity--consequences for bioptic diagnosis].

During the last several decades, immunohistochemical studies of tumors, along with other approaches, have suggested that the clinical and biological progression results, at least in part, from the sequential appearance within the neoplasm of cellular subpopulations whose new characteristics reflect specific somatic genetic changes. However, CNS may provide a different microenvironment for activation and proliferation than other tissues. The tissue-specific distribution of intermediate filament proteins, in particular the keratins, permits their use as marker in histopathology, but several important exceptions are recognized. In this connection, it is of interest that, according to the other reports, glial tumors may be positive for different anti-keratin antibodies. However, the gliomas did not show an immunoreaction in any of the cases when HEA-125 and Ber-EP4 were applied. The great number of multihormonal pituitary adenomas and possible change of the immunohistochemically detectable hormone status in cases of recurrent tumors have particularly re-emphasized the need for new thinking about patterns of classification. The diagnosis of malignant melanoma has been considerably facilitated recently by the introduction of immunohistological labelling with antibodies selective against melanoma antigen (HMB-45). Our results confirmed the necessity of cautious interpretation of HMB-45 immunoreactivity because a HMB-45 expression can be observed in several non-melanotic tumors.

Adenoma↗

PubMedDate not supplied

[Proliferative and differentiation potential of individual clones derived from bone marrow stromal precursor cells].

We present the results of a study on the proliferative and differentiation potential of individual clones of stromal fibroblasts growing in monolayer cultures of bone marrow cells. Each precursor cell yielding a large colony in primary culture is capable of up to 34 doublings in vitro. The transplantation of clones or monoclonal strains of stromal fibroblasts into the open system results in the formation of microenvironment consisting of the bone and reticular tissue and is suitable for the differentiation of all three lines of hemopoiesis. Evidence has been obtained that, in a closed system, individual clones are capable of differentiation into the bone, cartilaginous, and reticular tissues. In other words, the adult organism has a common cell precursor for these tissues.

Animals↗

PubMed1989

[A correlation between the abilities of tumor cells to produce GM-CSF and form metastasis].

Nearly a half of murine transplantable tumor cells upon in vitro culture were found to produce granulocyte/macrophage-colony stimulating factor-(GM-CSF) in the cultured fluids and express its mRNA in the cell. Tumor cells producing GM-CSF and expressing its mRNA in culture, when inoculated intramuscularly in the syngenic mice, developed severe metastasis with large tumor nodules in the lung and lymph nodes, whereas those producing no GM-CSF developed no visible metastatic nodules. With a possible mechanism involved in this intimate correlation between the production of GM-CSF and tumor metastasis, a role of GM-CSF as an autocrine growth factor in tumor growth and an immunopathological effect of GM-CSF on microenvironment of tumor cells in the metastatic tissues were discussed.

Animals↗

PubMedDate not supplied

[Effect of hypokinesia on the osteogenetic and hematopoietic functions of the bone marrow in mice. The ectopic bone model].

Using heterotrophic transplantation of syngenic bone marrow under the renal capsule, the effect of hypokinesia on osteogenic and hemopoietic cells-precursors as well as on de novo formed bone marrow was investigated. Altogether 16 experiments were performed, employing 260 recipients and 200 donors in two modifications: 1) bone marrow from animals exposed to hypokinesia for 3 days or 3 weeks (stage I or II of the general adaptation syndrome) was implanted to intact mice; 2) recipients who 5 to 7 day before exposure were implanted with bone marrow from intact donors were hypokinetic for 3 weeks. It was found that determined bone marrow precursors of osteogenic tissue as well as cells transferring hemopoietic microenvironment remained insensitive to hypokinesia. Three-week hypokinesia produced noticeable inhibition of osteogenesis and hemopoiesis. It is concluded that the stress-reaction plays the leading role in the changes that develop in hypokinetic mice.

Animals↗

PubMed1981

[Effect of bone marrow trypsinization on the efficiency of fibroblast colony formation in monolayer cultures].

Stromal bone marrow mechanocytes responsible for microenvironment transfer during heterotopic transplantation of hemopoietic tissue from fibroblast clones in monolayer cultures. Fibroblast colony forming cells (FCFC) are readily released from tissue structures together with hemopoietic elements and are contained in bone marrow cell suspension at a concentration of 1 x 10(-5)-10 x 10(-5). Pretreatment with trypsin of bone marrow fragments increases the content of FCFC in bone marrow cell suspension. Trypsin releases from the bone marrow and additional fraction of FCFC (trypsin-dependent FCFC), which are more strongly bound to tissue structures and are likely to be injured in the course of routine suspension of hemopoietic tissue fragments. The ratio of the number of trypsin-independent and trypsin-dependent FCFC is approximately 1 : 10.

Animals↗

PubMed1993

Expression and function of adhesion receptors on normal B cells and B cell non-Hodgkin's lymphomas.

A large number of molecules have been identified and characterized which mediate (1) homing of lymphoid cells to lymphoid tissues; (2) localization of cells within distinct microenvironments; and (3) cell-cell and cell-matrix interactions within those microenvironments. B lymphocytes express these adhesion receptors during stages of normal ontogeny. Malignant B cells can also express these adhesion molecules, and they probably serve a "normal" function in a neoplastic state. However, the aberrant expression and/or function of adhesion receptors may in part explain the clinical and biological behavior of these diseases. Further insight into the normal function of these surface molecules may provide novel approaches with which to consider the regulation of growth and dissemination of these cells in vivo, thereby suggesting new therapeutic approaches.

B-Lymphocytes↗

PubMed1995

Eicosanoids in rheumatoid arthritis.

Eicosanoids are potent mediators in the cellular microenvironment. Eicosanoids have different effects depending on tissue or organ, the polyunsaturated fatty acid content of the diet of the individual, and the net effect of local microenvironmental factors--as eicosanoids, cytokines, and hormones modulate each others' effects through a complex, multilevel network of interactions. In general, eicosanoids have significant net proinflammatory effects. In RA, the net proinflammatory effects of the prostanoids is underscored by the effectiveness of the cyclooxygenase antagonists (NSAIDs), and recent data indicate a proinflammatory effect of the leukotrienes. Changes in the dietary polyunsaturated fatty acid composition to increased intake of marine n-3 fatty acids and/or dihomogamma-linolenic acid may favorably modulate eicosanoid synthesis towards less inflammatory or antiinflammatory eicosanoids and may ameliorate disease activity in RA. Recent advances in the biochemistry and molecular biology of the eicosanoid receptors and the synthetic pathways of eicosanoids will provide opportunities for advances in the therapeutics for RA, including selective cyclooxygenase (PGHS-2) antagonists, selective eicosanoid receptor antagonists and agonists, and selective inhibitors of PGH2 isomerases and enzymes of the 5-lipoxygenase pathway.

Arthritis, Rheumatoid↗

PubMedDate not supplied

[Morphologic structural characteristics of the hematopoietic microenvironment in patients with multiple myeloma].

The authors' investigations found plasmocytic infiltration of bone marrow and marked resorption of bone tissue in patients with multiple myeloma (MM). Instead of the expected reduction in bone marrow volume the latter slightly increased. MM patients have significantly higher quantity of endosteal stromal cells, accumulations of osteoblastic cellular elements considered as initial osteogenesis. A close correlation was revealed between bone tissue volume, number of erythroid elements in bone marrow and red cell count in peripheral blood. Volume of fatty tissues in MM patients is low. MM patients demonstrate pronounced morphofuctional disturbances in hemopoietic microenvironment of bone marrow.

Adult↗

PubMed1997

Sjögren's syndrome. Controversies and progress.

Diagnostic criteria for Sjögren's syndrome (SS) are required by both physicians and patients to (1) provide a rational basis for their symptoms, assess their prognosis, and guide therapy; (2) identify a group of patients who are most likely to share a common etiopathogenesis, in order to identify those genetic and environmental factors that are crucial in pathogenesis; (3) fill out the myriad medical insurance forms that require a diagnosis code; and (4) serve as a "shorthand" code that alerts specialists in different fields (oral medicine, ophthalmology, and a variety of specialists in internal medicine) to search for particular clinical problems found in the SS patient. The key question in this article is whether the term "Sjögren's syndrome" should apply to a rather restricted group of individuals (those with an autoimmune basis for exocrinopathy) or to a rather large group of individuals who share a similar symptom complex of dry eyes and mouth. Primary SS, as defined by San Diego criteria, is a systemic autoimmune disease that is characterized by keratoconjunctivitis sicca and xerostomia resulting from lymphocytic infiltrates of the lacrimal and salivary glands. The criteria for the diagnosis of SS continues to be controversial, leading to confusion in the clinical and research literature. It is important to distinguish SS (an idiopathic autoimmune process) from other processes including hepatitis C infection, retroviral infection, lymphoma, autonomic neuropathy, depression, primary fibromyalgia, and drug side effects that can result in sicca symptoms. Recent studies on pathogenesis of SS in human and animal models have examined the clonality of the T-cell infiltrates, the production of cytokines by lymphocytes and glandular epithelial cells, neuroendocrine and hormonal factors that affect glandular secretion, and the fine structure of antigens recognized by T cells and B cells. Studies in SS have allowed comparison of lymphocytes in blood and in the glandular tissue lesions; important differences in the gland microenvironment play an important role in the initiation and perpetuation of the autoimmune process. For example, apoptotic death depends on the balance of Fas, Fas ligand, nuclear factors (such as bcl-2, bax, and myc), cytokines, neuropeptides, and cell membrane interactions with extracellular matrix. Although increased rates of apoptosis may be present in the blood T cells of SS patients, some glandular T cells are resistant to apoptosis. Recent advances have led to improved understanding of signal transduction in response to cytokines and hormones that play a role in the local and systemic manifestations of SS.

Animals↗

PubMed1997

[Bone marrow structure and HIV infection].

Bone marrow hematopoietic tissue and stromal elements were characterized histologically on iliac bone trepanobioptats from 8 HIV infected patients. Signs of dyserythropoiesis, dysgranulocytopoiesis, dysmegakaryocytosis, focal accumulations of plasmocytes lymphoid and histiocytic cells were demonstrated. Changes of hematopoietic tissue were accompanied by reorganization of stromal microenvironment. Growth of intramedullar reticuline cells quantity and decline in number of endosteal stromal cells were found.

Adult↗

PubMed1993

Microenvironmental changes during axonal regrowth in the optic nerve of the myelin deficient rat. Immunocytochemical and ultrastructural observations.

Lesion-induced regenerative sprouting of CNS axons is accompanied by reactions of the supporting glia and vascular and connective tissue which may influence the extent of regeneration. In a previous report, it was shown that after crush injury, the amyelinated optic nerve of the myelin deficient (md) mutant rat contains greater numbers of regrowing axons proximal to the site of crush than that of normally myelinated littermates. The present study was designed to compare the response of the microenvironment, i.e. glial cells and vascular and connective tissue, in md and normally myelinated optic nerves 2, 4 and 6 days after crush injury. In unoperated normal optic nerves monoclonal antibodies to the HNK-1 carbohydrate labelled astrocytic processes at the ultrastructural level whereas in unoperated md mutants HNK-1 staining was restricted to axonal surfaces. Immunoreactivity with monoclonal antibodies to stage-specific embryonic antigen-1 (SSEA-1) was confined to astrocytic surfaces in both md and wildtype animals. After axotomy of md optic nerves regrowing axons were more numerous in the proximal site of the crush and extended further into the lesion than in wildtype animals. In both md and wildtype rats regrowing axons were HNK-1-positive. In md rats strong reaction with antibodies to laminin and fibronectin was only seen in 6-day-old lesions of md rats whereas immunoreactivity was less distinct in operated littermate controls. Immunolabelling was obviously associated with blood vessels, since crush lesions in both md and wildtype rats were Schwann cell-free as assessed by electron microscopy and immunocytochemistry. In both operated md and normal littermates crush lesions contained degenerating astrocytes as well as reactive astrocytes in which the intermediate filaments of the perikarya failed to stain immunocytochemically for GFAP, vimentin, desmin, and a common determinant of intermediate filaments. In contrast, reactive astrocytes in the lesion site of normally myelinated rats expressed the SSEA-1 antigen intracytoplasmically whereas in md mutants astrocytes were completely SSEA-1-negative. Infiltration of crush lesions by macrophages was less extensive in md rats than in normal littermates. However the overall content of macrophages in the peritoneal cavity was also reduced. The present study demonstrates that (1) md optic nerves lack HNK-1-reactive astrocytes; (2) in the axotomized wildtype optic nerve impaired axonal regrowth may be associated with distinct immuno-phenotypes of the supporting glial cells, i.e. SSEA-1-positive astrocytes; (3) laminin and fibronectin seem not to be essential for improved axonal regrowth in md rats.

Animals↗

PubMed2001

Immunopotentiation of DNA vaccine against herpes simplex virus via co-delivery of plasmid DNA expressing CCR7 ligands.

The CCR7 ligands, secondary lymphoid tissue chemokine (SLC) and Epstein-Barr virus-induced molecule 1 ligand chemokine (ELC), were recently recognized as key molecules in establishing functional microenvironments for the initiation of immune responses in secondary lymphoid tissue. Here, we investigated the effect of CCR7 ligands-DNA administration on systemic and mucosal immune responses to plasmid DNA encoding gB of herpes simplex virus (HSV). Systemic co-transfer of both CCR7 ligands enhanced serum gB-specific IgG Ab but failed to elicit enhancement of distal mucosal IgA responses. In contrast, mucosal co-transfer provided significant increases of distal mucosal IgA responses. CCR7 ligands also enhanced T cell-mediated immunity as measured by CD4+ T helper cell proliferation and CD8+ T cell-mediated CTL activity. Of particular interest, is the observation that SLC significantly increased the production of Th1-type cytokines (IL-2 and IFN-gamma) (P<0.05), whereas ELC increased the production of both Th1-type and Th2-type (IL-4) cytokines (P<0.05). Moreover, co-vaccination of CCR7 ligands increased the number of dendritic cells in secondary lymphoid tissue. These data indicate that CCR7 ligands may prove to be useful adjuvants for genetic vaccination against intracellular infection as well as cancer.

Adjuvants, Immunologic↗

PubMed2004

Dual function of the extracellular matrix: stimulatory for cell cycle progression of naive T cells and antiapoptotic for tissue-derived memory T cells.

Tissue T cells encounter Ag in a distinct microenvironment, where they are embedded in the interstitial extracellular matrix (ECM). In contrast, while naive T cells are exposed to Ag in the lymph node, immediately after naive T cells are activated they must extravasate into the ECM to function effectively. Because integrin-mediated adhesion to the ECM modulates cell cycle progression and survival in adherent nonimmune cells, we hypothesize that blood and tissue-derived T cells have similarly adapted their behavior to their first or continued encounter with ECM. T cells from peripheral blood (PBT) and tissue (the intestinal lamina propria T cell (LPT)) were stimulated with anti-CD3-coated beads in the presence or absence of native ECM derived from intestinal fibroblasts, plate-immobilized fibronectin, or collagen type I. Native ECM and collagen, but not fibronectin, induced in anti-CD3 activated PBT a 4- to 5-fold increase in the entry, progression, and completion of the cell cycle over that triggered by anti-CD3 alone. Neutralizing beta1 integrin Abs abrogated this increase. None of these ECM proteins stimulated cell cycle progression in LPT. In contrast, anti-CD3 activation of LPT in the presence of native ECM and fibronectin reduced activation-induced cell death by 40%. These results demonstrate that naive and effector/memory T cells respond differently upon exposure to specific ECM components. When naive PBT encounter Ag in the context of ECM, their progression through the cell cycle is enhanced, favoring clonal expansion; while tissue T cell longevity may be mediated by interactions with the ECM.

Adjuvants, Immunologic↗

PubMed2006

Probing the role of multicellular organization in three-dimensional microenvironments.

Successful application of living cells in regenerative medicine requires an understanding of how tissue structure relates to organ function. There is growing evidence that presentation of extracellular cues in a three-dimensional (3D) context can fundamentally alter cellular responses. Thus, microenvironment studies that previously were limited to adherent two-dimensional (2D) cultures may not be appropriate for many cell types. Here we present a method for the rapid formation of reproducible, high-resolution 3D cellular structures within a photopolymerizable hydrogel using dielectrophoretic forces. We demonstrate the parallel formation of >20,000 cell clusters of precise size and shape within a thin 2-cm(2) hydrogel and the maintenance of high cell viability and differentiated cell markers over 2 weeks. By modulating cell-cell interactions in 3D clusters, we present the first evidence that microscale tissue organization regulates bovine articular chondrocyte biosynthesis. This platform permits investigation of tissue architecture in other multicellular processes, from embryogenesis to regeneration to tumorigenesis.

Animals↗

PubMed1983

Hemopoietic stromal precursors in long-term culture of bone marrow: II. Significance of initial packing for creating a hemopoietic microenvironment and maintaining stromal precursors in the culture.

Conversion of bone marrow cells to a single cell suspension prevents them from creating a hemopoiesis maintaining adherent cell layer (ACL) in culture. The ACL of such cultures is devoid of hemopoietic stromal precursors capable of transferring the hemopoietic microenvironment on implantation under the renal capsule of syngeneic mice. The regeneration of ACL after injury is possible in 1-wk-old, but not older, Dexter-type bone marrow cultures. The results prove the significance of the initial packing of the bone marrow cells in the differentiation of the hemopoietic stromal precursors. These data contradict previous reports which concluded that the structural orderliness of stromal tissue need not be preserved for the hemopoietic microenvironment to be transferred.

Animals↗

PubMed2006

Involvement of dendritic cells in the pathogenesis of inflammatory bowel disease.

In conclusion, during inflammation, DCs are likely activated by inflammatory signals and induced to migrate to T cell zones of organized lymphoid tissues where the cells induce T cell responses. In addition to their established role in T cell priming and the induction of tolerance, DCs may act to enhance (or possibly suppress) T cell responses at sites of mucosal inflammation. Determining the importance of DCs in this regard, as well as establishing a potential role for DCs in continuous activation of naive or central memory cells in lymph nodes draining inflammatory sites, will elucidate the role of DCs as a potential therapeutic target for chronic inflammatory diseases, like IBD. Resident intestinal macrophages are noninflammatory and do not efficiently present antigens to intestinal T cells, yet are avidly phagocytic and able to kill internalized organisms. During intestinal inflammation, monocytes are recruited from the blood, become inflammatory macrophages in the inflamed tissue, and are major contributors to tissue destruction and perpetuation of inflammation via their production of chemokines and pro-inflammatory cytokines. Macrophages may also contribute directly to DC activation and maturation, which would drive DCs to present antigens from the bacterial flora to T cells locally within tissue or to more efficiently traffic to T cell zones of lymphoid tissue. Thus, DCs and macrophages have evolved functional niches that promote cooperation in the prevention of untoward intestinal inflammation in the steady state and in the eradication of invasive microorganisms during infection. The balance between suppressing inflammation and promoting host defense is altered in humans with IBD allowing a persistent inflammatory response to commensal bacteria. Based on studies from animal models, the pathogenesis of IBD likely involves either the lack of appropriate regulation from T cells, or an over-production of effector T cells. The end result of these potential mechanisms is the abnormal induction and/or survival of effector T cells and the production of factors such as cytokines by inflammatory macrophages and neutrophils that result in tissue destruction. The destructive process likely involves normally tolerizing DCs, which in the microenvironment of the inflamed mucosa activate T cell responses to normal flora in both draining lymphoid tissues and at sites of inflammation, with macrophages and neutrophils contributing the bulk of inflammatory and destructive cytokines.

Animals↗