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PubMed1989

Improved hematopoiesis in anemic Sl/Sld mice by splenectomy and therapeutic transplantation of a hematopoietic microenvironment.

The ability of a clonal hematopoiesis-supportive bone-marrow stromal cell line GBlneor to engraft and alter the microenvironment-induced anemia of Sl/Sld mice was studied. Prior to stromal cell transplantation, Sl/Sld mice received 1 Gy total body irradiation (TBI) and 13 Gy to the right hind limb. Two months after intravenous (IV) injection of 5 x 10(5) GBlneor cells, 54.4% +/- 17.0% donor origin (G418r) colony-forming cells were recovered from the right hind limb of Sl/Sld mice. Long-term bone marrow cultures (LTBMCs) established from GBlneor-transplanted mice produced 189.5 CFU-GEMM-forming progenitors/flask over 10 weeks compared with 52.7 +/- 6.2 CFU-GEMM forming progenitors/flask from irradiated nontransplanted Sl/Sld mice. A partial correction of macrocytic anemia was detected 2 months after GBlneor transplantation in splenectomized, irradiated Sl/Sld mice (HgB 7.2 +/- 0.4 g/dL; MCV 68.3 +/- 7.0 fL) compared to splenectomized, irradiated, nontransplanted Sl/Sld mice (HgB 5.5 +/- 1.1 g/dL; MCV 76 +/- 8.5 fL) or control Sl/Sld mice (HgB 5.4 +/- 0.5 g/dL; MCV 82.4 +/- 1.3 fL). Mean RBC volume distribution analysis showed a 2.5-fold increase in percentage of peripheral blood RBCs with MCV less than or equal to 45 fL and confirmed reduction of the MCV in splenectomized-GBlneor-transplanted mice compared to control Sl/Sld mice. A hematopoiesis-suppressive clonal stromal cell line derived from LTBMCs of Sl/Sld mice (Sldneor) engrafted as effectively (43.5% +/- 1.2% G418r CFU-F/limb) as did GBlneor cells (38.3% +/- 0.16% G418r CFU-F/limb) to the irradiated right hind limbs of C57Bl/6 mice. LTBMCs established after 2 or 6 months from Sldneor-transplanted mice showed decreased hematopoiesis (182 +/- 12 [2 months] and 3494.3 +/- 408.1 [6 months] CFU-GEMM forming progenitors/flask over 10 weeks) compared to those established from GBlneor-transplanted mice (5980 +/- 530 [2 months] and 7728 +/- 607, [6 months] CFU-GEMM progenitors forming/flask). Thus, transplantation of clonal bone-marrow stromal cell lines in vivo can stably transfer their physiologic properties to normal or mutant mice.

Anemia↗
PubMed1989

Hematopoiesis on cellulose ester membranes. XI. Induction of new bone and a hematopoietic microenvironment by matrix factors secreted by marrow stromal cells.

Cellulose ester membranes (CEM) were coated with stromal cells from bone marrow (BM) or bone and implanted intraperitoneally (IP) in CAF1 mice for intervals of 1 to 6 months. Previous studies indicated that matrix factors [glycoproteins (GPs), proteoglycans (PGs), and glycosaminoglycans (GAGs)] were secreted by the regenerating stromal cells and adsorbed by the CEM. After 1 to 6 months, the CEMs were removed, scraped free of adherent cells, and irradiated in vitro with 40 Gy. The scraped and irradiated CEMs were then reimplanted IP or subcutaneously (SC) for periods of 1 to 6 months in secondary syngeneic murine hosts. They were then removed for histologic study. CEMs reimplanted in SC sites developed bone and hematopoiesis as early as 1 month after implantation. Maximum hematopoiesis and bone formation was observed after 3 months. CEMs coated during the initial implantation with bone-derived stromal cells contained more bone and hematopoietic cells than did CEMs coated with marrow-derived stromal cells after SC implementation. Neither the CEMs coated with bone stromal cells nor those coated with marrow stromal cells developed new bone or trilineal hematopoiesis after being implanted IP. A few CEMs contained small foci of granulopoiesis only. We conclude that noncellular matrix substances deposited on CEMs by bone, and to a lesser degree by marrow cells, can induce prestromal cells in the SC tissues to produce a microenvironment suitable for trilineal hematopoiesis.

Animals↗
PubMedDate not supplied

[Distribution of aromatic amino acid residues according to the character of their microenvironment and the dynamics of the conformational properties of the protein molecule C1q].

The distribution of aromatic amino acid residues in the Clq molecule according to their microenvironment was studied by the methods of difference thermal and solvent perturbation spectroscopy, fluorescence and chemical modification. Out of the three tryptophan residues located in the globular part of A- chain one residue is completely exposed on the surface, while other two are only partially exposed to a solvent. Chemical modification of tryptophanyls significantly affects the hemolytic activity of Clq, that may evidence for the formation of immunoglobulin-binding sites with participation of A- chains as well as for the location of, at least, one of the three tryptophan residues in A- chain close to the immunoglobulin-binding site or even participation in the formation of the latter. The average rotation relaxation time of tryptophanyls estimated from the data on fluorescence is 210 +/- 10 ns. It specifies mobility of the globular and collagen parts of the molecule.

Amino Acids↗
PubMed1988

Influence of organ microenvironment on pigmentation of a metastatic murine melanoma.

The purpose of these studies was to investigate the relationship of the host microenvironment to the metastatic and pigmented phenotypes of the SW-1 variant of the murine K-1735 melanoma. The SW-1 subline was isolated from an amelanotic lung metastasis in a C3H/HeN mouse given an s.c. injection of the K-1735 melanoma. Cells of this line were highly metastatic and produced tumor deposits in many organs. In all sites except the brain, these lesions were predominantly amelanotic. K-1735 SW-1 cells were isolated from metastases in various organs and subsequently reinoculated into normal syngeneic recipients. Whereas the metastatic phenotype remained stable and thus was heritable, pigmentation was unstable and appeared to be modulated by the site of tumor growth. Further differences in the phenotype of K-1735 SW-1 cells growing in vivo and in culture were revealed by assays for tyrosinase activity. K-1735 SW-1 cells growing in culture did not produce melanin nor did they respond to agents that can stimulate melanin production in another mouse melanoma, the B16 line. K-1735 SW-1 cells do not, however, lack tyrosinase, since these cells are capable of producing melanin when growing in certain organs in vivo. We conclude that the host organ environment may influence a phenotype of malignant melanoma cells, i.e., pigmentation. These findings also suggest caution when extrapolating the results of in vitro biochemical assays to properties of tumor cells growing in vivo.

Animals↗
PubMed1985

Hematopoiesis on cellulose ester membranes (CEM). VIII. Studies of the hematopoietic microenvironment developing on intraperitoneally implanted CEM in S1/S1d and S1+/S1+ mice.

Cellulose ester membranes (CEM) were implanted intraperitoneally into S1/S1d and S1+/ S1+ mice. These CEM rapidly became coated with peritoneal cells capable of supporting primarily granulocytic colony development after seven days. S1/S1d-coated CEM showed a diminished capacity to support colony development compared with S1+/ S1+ CEM, perhaps reflecting the defect in the hematopoietic microenvironment of these mice. Marrow cells from S1+/S1+ and S1/S1d mice generated similar numbers of colonies on S1+/S1+ CEM. When CEM were transferred from a primary to a secondary host there was a tendency to remodel the CEM toward the characteristics of the secondary host. Peritoneal cells coating CEM from S1/S1d mice had less phagocytosis of yeast particles than peritoneal cells from S1+/S1+ mice. The cell coat on the membranes from S1/S1d mice was fewer cell layers in thickness than those on membranes coated in S1+/ S1+ mice.

Anemia, Macrocytic↗
PubMed1987

Immunoregulation in the Peyer's patch microenvironment. Cellular basis for the enhanced responses by the B cells of X-linked immunodeficient CBA/N mice.

The Peyer's patches (PP) of X-linked immunodeficient (xid) CBA/N and hemizygous (CBA/N X DBA/2)F1 (CDF1) male mice contain a B cell subpopulation that expresses the Lyb-5 maturational marker and is responsive to type 2 and T cell-dependent antigens in vitro, a B cell phenotype which is absent from the spleens of xid mice. Experiments reported here show that xid spleen B cells co-cultured with B cell-depleted PP cells from xid mice differentiated into specific plaque-forming cells in response to trinitrophenyl-Ficoll (type 2) and sheep erythrocytes (T cell-dependent). Two cell types were involved in this normalization of xid B cell responses. An accessory cell activity present in the PP, but not the spleens, of both CDF1 male (xid) and CDF1 female (normal) mice was required for the response to either the type 2 or T cell-dependent antigens. In the presence of this PP accessory cell, T cells from the PP of either xid or normal mice supported responses to both classes of antigens. In contrast, T cells from the spleens of xid mice did not support the response to trinitrophenyl-Ficoll, although the splenic T cells from normal mice did synergize with PP accessory cells in allowing plaque-forming cell development by xid B cells to this type 2 antigen. The xid PP T cell activity required for the type 2 response by xid B cells was present in the Ly-1+, Lyt-2- subpopulation, and the xid PP accessory cell activity was provided by an enriched population of dendritic accessory cells. These results demonstrate the the lymphoreticular cells comprising the PP microenvironment provide effective support for the differentiation of xid B cells in response to type 2 and T cell-dependent antigens.

Animals↗
PubMed1988

A novel T-lymphocyte molecule that may function in the induction of self-tolerance and MHC-restriction within the human thymic microenvironment.

T-cell differentiation is known to take place in the thymus, but the precise mechanisms involved remain unresolved. In order to analyse the role of the thymic microenvironment in thymocyte maturation and generation of the T-cell repertoire, we have raised monoclonal antibodies (mAb) to thymic stromal cells, and with these can recognize, in the non-lymphoid component of the thymus, several antigenically distinct compartments. One mAb, MR6, binds to both the cortical epithelium and medullary macrophages/dendritic (M phi/DC) cells in sections of the human thymus. Recently, the molecule detected by MR6 has also been detected at low levels on the surface of T lymphocytes. We now report that this molecule has a relative molecular mass of 145,000 (p145-MR6) and that this appears to be the same for both thymic lymphocytes and stromal cells. Functional studies show that mAb MR6 inhibits both the antigen-specific and the IL-2-induced proliferative response of MHC class II-restricted cloned helper T cells and peripheral blood mononuclear cells (PBMC). These results suggest that the molecule to which mAb MR6 binds could be responsible for the inhibition of T-cell proliferation to self-antigens, and hence may be involved in tolerance induction and MHC restriction.

Animals↗
PubMed1988

Heparan sulfate is necessary for adhesive interactions between human early hemopoietic progenitor cells and the extracellular matrix of the marrow microenvironment.

Human hemopoietic blast colony-forming cells (BI-CFCs) recognize and adhere to the extracellular matrix (ECM) produced by marrow-derived stromal cells in vitro. We have investigated the requirements for this interaction by testing the capacity of BI-CFCs to adhere to ECM components under a variety of conditions. Binding was prevented completely by prior treatment of stromal ECM with nitrous acid, in large part by treatment with heparitinase or hyaluronidase, and slightly by treatment with chondroitinases. Whereas heparan sulfate isolated from marrow stromal cultures effectively blocked binding, heparan sulfate from bovine kidney did not. Chondroitin sulfate and hyaluronic acid did not have any effect in this test. In contrast, collagen was not sufficient for the interaction because dishes coated with collagen type I or IV did not act as adhesive surfaces for BI-CFCs. Ligands for integrin receptors (e.g., fibronectin) did not participate in BI-CFC binding because the synthetic pentapeptide glycine-arginine-glycine-asparagine-serine did not compete with stroma in binding BI-CFCs. These findings indicate that heparan sulfate in the bone marrow microenvironment is necessary for BI-CFC binding to ECM and may contribute to localizing hemopoietic stem cells in hemopoietic tissue.

Antigens, Surface↗
PubMedDate not supplied

[Study of the effect of the microenvironment on magnetic resonance parameters of spin-labeled human serum albumin in a 2-mm ESR range].

Basic values of g-tensor and Azz component of HF tensor of two spin labels and spin probe on HSA and nitroxyl radicals HO-15, HO-34 in the solvents of different polarity were measured by 2 mm band ESR of 2 mm range. Magnetic-resonance parameters of liophylized and water-solved spin-labeled HSA were shown to correspond to the parameters of the solvents of the label HO-15 and HO-34 in ethyl alcohol and water. A conclusion was drawn concerning the identity of microenvironment of the nitroxyl fragment of liophylized HSA and frozen solution of the label HO-15 and HO-34 in ethyl alcohol and solvatation of the nitroxyl fragment of spin-labeled HSA and label HO-15 (HO-34) by water molecules.

Chemical Phenomena↗
PubMedDate not supplied

[The role of thymic microenvironment in T-cell maturation].

The role played by different components of thymic microenvironment in T-cell-maturation is examined: antibodies to a soluble thymic factor (STF) were thus shown to inhibit T-cell maturation in the chicken while incubation of bursal "null" cells with STF could induce the differentiation of some of them into T cells. In addition to STF, whose properties resemble those of other soluble thymic factors, an insoluble thymic factor (ITF) is described: it is localized mainly in membranes associated with medullary blood vessels, and its injection to mice provokes an influx of marrow stem cells into the thymus.

Animals↗
PubMed1988

Hierarchical organization of hematopoietic microenvironments: role of proteoglycans.

The orderly process of hematopoietic cell differentiation depends on the organization of specific microenvironments which function by assembling progenitor cells and appropriate concentrations of necessary growth factors. We propose that this organization involves a spectrum of microenvironmental complexity concomitant with changing cellular requirements, that it is achieved by the extracellular matrix produced by marrow stromal cells, and that its specificity is conferred by the heterogeneity intrinsic in the conformation of proteoglycans and their constituent glycosaminoglycans.

Animals↗
PubMed1988

Human thymic epithelium in culture: an experimental model for the study of thymic microenvironment.

The thymus plays a central role in the differentiation of T-lymphocytes. During the past years several in vitro models have been developed for the elucidation of the functional role of different thymic stromal cells. After reviewing the literature, the authors discuss: a) the in vivo and in vitro data on the structural organization of the thymus microenvironment, with particular reference to the epithelial cells; b) the endocrine function of the thymus; c) the interaction between the thymic epithelium and T-cell precursors. The experimental approaches to these problems are also discussed. In particular, the authors examine in detail the experimental aspects which are at present under investigation in their laboratories.

Animals↗
PubMed1988

Cell surface topography of thymic microenvironments.

In the thymus gland, differentiating T lymphocytes interact, at various levels of differentiation, with the thymic stroma. This type of interaction is generally thought to be important in the "education" of T lymphocytes. This paper focuses on the complexity of the thymic stroma and identifies various types of lympho-stromal interactions, using scanning electron microscopy as a tool. We show heterogeneity at the level of stromal cells in both thymic compartments, the cortex and medulla. In addition, specialized epithelial reticulum occurs in the subcapsular area, known to be the site where immature thymocytes proliferate and differentiate. Here "basket" type epithelial structures retain groups of thymocytes. Furthermore, virtually closed lympho-stromal complexes, resembling "thymic nurse" cells are located in this area. Lymphoid cells show signs of active migration between epithelial reticular cells. These cells even transit from or into the thymic nurse cell-like structures. The medulla is characterized by other stromal elements, such as short fat-bodied epithelial cells and bone marrow derived interdigitating reticular cells. In addition, cysts lined by ciliated columnar epithelial cells occur in the corticomedullary junction area. The physiologic significance of these various microenvironments in the various steps of T cell differentiation is discussed.

Animals↗
PubMed1987

[Myelofibrosis. Pathology of the microenvironment].

Myelofibrosis is the most representative model of the association between the hemopoiesis failure end the abnormalities of the myeloid microenvironment. Long term culture in Dexter's liquid system is a good model for the in vitro study of myeloid differentiation. An experimental in vitro system using an irradiated under layer and aplastic patients plasma has yielded some preliminary results allowing the production of megakaryocytic colonies. Close contact between these colonies and the fibroblasts or stromal cells in the adherent layer could probably be used for the study of the interrelation between the stromal abnormalities and myeloid pathology.

Hematopoietic Stem Cells↗
PubMed1986

Generation of stable cellular phenotypes in a human malignant cell line conditioned by alterations in the cellular microenvironment.

Microenvironmental conditions may result in phenotypic changes of malignant cells and/or selection of preexisting variants with a growth advantage under the new growth conditions. The present study was initiated to evaluate the stability of changes in crucial cellular attributes as induced in vivo by nonimmunological mechanisms. Expression of major histocompatibility antigens, membrane immunoglobulin, in vitro growth rate, chromosome complement, and modal chromosome number were thus examined in a human B-lymphoma line (RH-L4) prior to and after short-term passage through the peritoneal cavity or spleen of newborn mice. Seven sublines (four from spleen and three from peritoneal cavity) of RH-L4 cells were established after the passage. These lines were found to differ phenotypically from the original line in respect to several or all of the attributes that were studied. These differences were stable for greater than 100 cell generations. Analyses of major histocompatibility complex Class II antigen expression indicated that the modulation of this antigen was independent of the immunological competence of the mice and unrelated to cell cycle-dependent variations. The emergence of the variant sublines seemed not to reflect a microenvironmentally determined selection of minority subpopulation in the original RH-L4 lymphoma line but, instead, induced by the growth conditions in the cellular microenvironment in the mouse. It is suggested that inductive processes may be of importance in the generation of phenotypic diversity within individual tumor cell populations, including the generation of phenotypic variants with high metastatic activity.

Animals↗
PubMed1987

Functional maturation of murine B lymphocyte precursors. II. Analysis of cells required from the bone marrow microenvironment.

The development of mature B cells in cultures of early B cell precursors depends on the presence of a confluent adherent bone marrow (aBM) cell layer. Adherent and sIgM+ cell-depleted bone marrow (BM) from untreated or 5-fluorouracil-pretreated donors or day 12 fetal liver cells were used as precursor cell populations. When adherent cells from thymus or highly enriched BM-derived macrophages were co-cultured with precursor cells, mature B cells were not developed. Similarly, aBM cell layers generated in the presence of hydrocortisone and horse serum were unable to support aBM cell-dependent precursor differentiation, even though cortisone was removed before the addition of precursor cells. In contrast, this type of microenvironment promoted the differentiation of precursor of myeloid cell lineages. Repeated treatment of established aBM cell populations with a monoclonal anti-macrophage antibody (31.3, known to recognize a surface marker on a subset of BM macrophages) and complement abolished the capacity of otherwise functional aBM cells to sustain the development of B cell precursors. Macrophage-depleted aBM cells regained their function after supplementation with highly enriched BM-derived macrophages grown in vitro. Limiting dilution analysis of aBM cells in microcultures containing saturating numbers of early B cell progenitors also suggests the participation of more than one cell type in the BM cell population. In conclusion, differentiation of early B cell progenitors requires macrophages in addition to at least one additional cell type contained in the aBM cell population.

Animals↗
PubMed1986

Phenotypic characterization of the thymus microenvironment study of the human thymus architecture.

Phenotypic characterization of the human thymic microenvironment shows the heterogeneity of the epithelial component. Using monoclonal antibody L191, we define here a new antigen common to the flat epithelial cells lining up the thymic capsule and septum, stellate epithelial cells from the subcapsular area and the medulla (M), but lacking on stellate epithelial cells from the inner cortex. Thus, this cell population can be characterized by a series of antigens (TE-4 and P19--shared with HTLV--previously described by B. Haynes et al.) which reflect a common differentiation program--including neuroendocrine specialization--with remarkable differences in the expression of these antigens, occurring during ontogeny and after birth. Another Ab we obtained shows particularities in the cytoskeletal organization of this cell population. Finally the organization of the mesenchymal component was also investigated with a third, anticollagen, antibody. A striking observation we made, using these antibodies, was the relationship between the thymic septum and flat epithelial cells with medullary and Hassal's body (HB) epithelial cells: septae deeply penetrate the medulla so that flat epithelial cells come into direct contact with medullary epithelial cells; in addition, HB are in close contact with the deepest portion of the septae, often separated solely by a single stellate cell. This architectural organization might be related to the differentiation--regeneration process of the thymic epithelium.

Antibodies, Monoclonal↗
PubMed1987

Clothing surface area as related to body volume and clothing microenvironment volume.

The evaluation of clothing surface area becomes important in analyses of heat exchange between the clothed body and its environment. The evidence accumulated in the studies of radiation area has led to the conclusion that the ratio of clothing surface area to body surface area (fcl) may be defined as a function of clothing insulation. However, the effects of clothing fit have been disregarded. Radiation area factors (Ar/AD) were derived from pictures of five subjects wearing four different helicopter pilot suits. While sitting on a seat suspended in the center of a box-shaped frame, photographs were taken of the subjects with a fish-eye lens at 90 equidistant points on the six sides of the frame. The derived Ar/AD of 0.7 +/- 0.18 for the unclothed subjects closely agreed with that reported by Fanger, while it scattered in a relatively wide range for a given suit. The present study proposes a new approach for predicting fcl as related to body volume and the clothing microenvironment volume. The predictions show a good correlation with the values derived from the photographs. It is, therefore, suggested that improvement in the prediction of fcl has been achieved by incorporating clothing fit.

Anthropometry↗