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At least 991 records · Page 55Linked to original sources
PubMed1997

The urokinase-receptor (CD87) is expressed in cells of the megakaryoblastic lineage.

Megakaryocytopoiesis is governed in the bone marrow microenvironment by cellular interactions that include various adhesion receptor systems and pericellular proteolysis for proper regulation of cell motility and differentiation. In order to define the role of cell surface molecules required for these processes, we searched for protease receptors on these cells. In an in vitro system utilizing different cell lines of the megakaryoblastic lineage (MEG-01, Dami), low level surface expression of the urokinase (uPA) receptor was noted. Following stimulation with phorbolester (PMA), a 3-6 fold higher expression of uPA receptor over a period of up to 5 days could be observed by fluorescent activated cell-sorting as well as by direct ligand-binding of amino-terminal fragment of uPA or vitronectin. Together with elevated expression of alpha IIb beta 3-integrin (glycoprotein IIb/IIIa complex), double immuno-fluorescence staining of stimulated cells confirmed the increased cell surface localization of uPA receptor. Semi-quantitative RT-PCR, ligand blot analysis and measurement of cell-bound proteolytic activity revealed a differentiation-dependent upregulation of the uPA receptor expression in megakaryoblastic cell lines as in monocytic cells. Due to its glycolipid anchorage, incubation with phosphatidylinositol-specific phospholipase C reduced uPA receptor-mediated ligand binding by about 60%, uPA receptor mRNA was expressed in cultured megakaryocytes derived from bone marrow, whereas no uPA receptor mRNA was detectable in platelets. These results indicate a differentiation-dependent increase in the expression of uPA receptor in megakaryoblastic cells. The characteristics of surface expression and functionality of the receptor on megakaryocytic cells may influence their maturation by regulating cellular communication in the bone marrow micro-environment.

Cell Differentiation↗
PubMed2002

Bone marrow immunoscintigraphy using technetium-99m anti-granulocyte antibody in multiple myeloma.

Conventional skeletal radiography and bone scan have certain limitations in the initial evaluation of bone and bone marrow lesions in multiple myeloma (MM). In this study we investigated the value of bone marrow immunoscintigraphy (BMIS) using anti-granulocyte monoclonal antibody (AGA) for the diagnosis of bone involvement of MM, in comparison with bone scan and skeletal radiography. Whole-body BMIS using technetium-99m-labelled AGA was performed in 22 MM patients (15 male, 7 female) and the imaging findings compared with those of skeletal radiography and (99m)Tc-methylene diphosphonate bone scan. The findings of bone marrow aspiration and serum biochemical findings were also compared with BMIS findings. Abnormal findings of BMIS were defined as presence of a focal photon defect in the axial skeleton or expansion of peripheral bone marrow. A total of 124 focal lesions were detected in 19 subjects (86%) by skeletal radiography, bone scan or BMIS. BMIS detected 92 lesions (74%) in 19 subjects, whereas skeletal radiography detected 58 focal lesions (47%) in 14 and bone scan 40 lesions (32%) in 11. Fifty-one (41%) of the 124 lesions were only seen on BMIS. Spine and pelvic lesions were better visualised by BMIS, whereas skull lesions were better seen with skeletal radiography, and bone scan detected more lesions in the ribs. Marrow expansion was noted in 15 subjects (68%) on BMIS, and its grade correlated with marrow cellularity and myeloma cell percentage in bone marrow aspirates ( P=0.0055 and P=0.0541, respectively). BMIS revealed abnormal lesions in one of three stage II patients and 17 out of 19 stage III patients. The number of lesions of the thoracolumbar vertebrae on BMIS was correlated with cellularity ( P=0.0393), but not with myeloma cell percentage ( P=0.1262). These findings suggest that the results of BMIS with (99m)Tc-labelled AGA correlate with clinical stage, and thus reflect the functional status of bone marrow in MM patients. BMIS might be useful for the detection of bone involvement of MM when skeletal radiography or bone scan is inconclusive, especially for vertebral lesions.

Adult↗
PubMed2005

Evidence for incorporation of bone marrow-derived endothelial cells into perfused blood vessels in tumors.

Recent studies have demonstrated that the cellular contribution of the bone marrow to tumor neovascularization is highly complex. In this context, the extent to which bone marrow-derived cells incorporate as bona fide endothelial (nonhematopoietic) cells into perfused tumor vessels, or any new vessels formed postnatally (vasculogenesis), is unclear. To this end, we developed models to characterize local vessel-derived and bone marrow-derived endothelial cells (BMD-ECs). Then, we characterized the BMD-ECs based on a set of endothelial markers and morphology. Finally, we quantified their contribution to perfused blood vessels in tumors using transplanted as well as spontaneous primary and metastatic tumor models. We demonstrate that BMD-ECs incorporate in perfused tumor vessels, and that this contribution varies with organ site and mouse strain.

Adenocarcinoma↗
PubMed1994

Peroxidase activity in murine and human hematopoietic progenitor cells: potential relevance to benzene-induced toxicity.

Peroxidases may be important in the mechanism of toxicity of a number of compounds including benzene, a chemical that has been associated with bone marrow toxicity and leukemia after chronic exposure. The major peroxidase in bone marrow is myeloperoxidase (MPO), which has been previously thought to be expressed at the promyelocytic stage of differentiation. Hematopoietic progenitor cells are important potential cellular targets of bone marrow toxins and leukemogens. We therefore examined peroxidase activity in both murine and human progenitor cells. Murine progenitor populations were purified as lineage-negative cells (> 99% enriched) and human progenitor populations were purified as CD34+ cells (> 95% enriched). Using conventional biochemical assays for peroxidase activity, murine and human progenitor cells were found to have 30% and 11% of the peroxidase activity of murine and human unpurified marrow, respectively. Peroxidase activity was confirmed in purified murine and human progenitor populations by flow cytometry using a 2,7-dichlorofluorescein assay, adapted to measure peroxidase activity. In addition, two-color flow cytometry of murine whole marrow using phycoerythrin-conjugated antibodies to lineage markers confirmed the peroxidase activity of the murine progenitor cell population. A reverse transcription-polymerase chain reaction assay was developed for MPO mRNA, which was detected in murine progenitor cells. These data show that MPO mRNA is expressed in murine progenitor cells and that both murine and human progenitor cells have marked peroxidase activity. These data may have relevance for studies of hematopoietic cell differentiation and for the examination of mechanisms underlying cell-specific toxicity in bone marrow.

Animals↗
PubMed1998

Cellular immune responses of human cadaver donor bone marrow cells and their susceptibility to commonly used immunosuppressive drugs in transplantation.

BACKGROUND: The cascade of immunological effects brought about by donor bone marrow cell (DBMC) infusions in human organ transplantation, especially in the context of continuous pharmacologic immunosuppression, is not fully understood. Yet, in inbred rodents and even primates, administration of specific bone marrow cells has caused a state of acquired immunologic tolerance. METHODS: In vitro mixed lymphocyte culture (MLC) and cell-mediated lympholysis (CML) culture systems were used to compare the responding and regulatory properties of DBMC and individual bone marrow cell subsets versus spleen cells in the presence or absence of pharmacologic immunosuppression. RESULTS: In the absence of immunosuppressive drugs, the DBMC proliferated in MLC and in response to phytohemagglutinin, but to a lower magnitude than donor spleen cells. In CML assays, DBMC failed to function as cytotoxic cells. Removal of both CD3+ and CD34+ cells together (not just singly) had to occur for complete abrogation of the proliferative response of DBMC evoked in the presence of allogeneic stimulating cells. Testing several experimental variables using flow cytometric analysis led to the conclusion that when purified DBMC CD34+ cells were placed in coculture with irradiated allogeneic peripheral blood mononuclear cells, such CD34+ cells give rise both to CD3- TCRalphabeta+ as well as to dimly staining CD3+ TCRalphabeta+ cells. Low pharmacologic concentrations of tacrolimus/cyclosporine (CsA) and mycophenolic acid (MPA) singly or in combination had no effect on the spontaneous proliferation of DBMC and had significantly less inhibitory activity on MLC responses of DBMC and its purified CD3+ or CD34+ subpopulations, compared with the responses of spleen cells. Moreover, the previously described regulatory effects of DBMC on the MLC responses of peripheral blood or splenic responding cells were not inhibited by these immunosuppressive drugs. CONCLUSIONS: Taken together, these results support the notion that in vitro DBMC subpopulations, which proliferate as responding cells in co-culture with x-irradiated allogeneic cells and which cause regulatory effects when added as a third component to MLC reactions, seem to be culture-generated lymphoid cell lineage(s) progeny of CD34+ cells. This possibly includes unique CD3+ "primitive" (dimly staining) T cells, which are not as inhibited in their function by tacrolimus/CsA and MPA, as are postthymic (splenic) T cells.

Antigens, CD34↗
PubMed1995

Bone marrow neutrophilia and suppressed bone turnover in human interleukin-6 transgenic mice. A cellular relationship among hematopoietic cells, osteoblasts, and osteoclasts mediated by stromal cells in bone marrow.

To elucidate the effect of interleukin-6 (IL-6) on bone and bone marrow (BM), human IL-6 transgenic mice (hIL-6 tgm) were produced. Their bone and BM were examined histologically, radiologically, histomorphometrically, and hematologically on a temporal basis. hIL-6 tgm showed histologically evident neutrophilia in BM. Increase in precursors of granulocytes and monocytes in hIL-6 tgm was demonstrated by an assay for colony forming unit in culture (CFU-C) of BM cells. Decrease in osteoblasts and osteoid and suppression of primary spongiosa formation were predominantly observed in hIL-6 tgm at 14 weeks old, the terminal stage of life for hIL-6 tgm. An assay for colony forming unit in fibroblastic (CFU-F) of BM cells revealed a decrease in osteoblast precursor (with regard to alkaline phosphatase-positive colonies) in hIL-6 tgm at 15 weeks old. Histomorphometry demonstrated a decrease of both osteoclast number and bone resorption in hIL-6 tgm. These results suggested that enhanced granulocytic hematopoiesis, suppressed bone turnover, and alteration of cellular population in stromal cells in BM occurred in hIL-6 tgm. Thus we provide new findings that facilitate understanding of cellular interrelationships among hematopoietic cells, osteoblasts, and osteoclasts mediated by stromal cells in BM.

Animals↗
PubMed1986

Increased chemotaxis of leukocytes from mice bearing tumors.

Increased chemotaxis toward activated serum was demonstrated by leukocytes from bone marrow, spleen, and peripheral blood of tumor-bearing mice as compared with those of normal mice. Increased chemotaxis was correlated with duration of tumor growth, which, in turn, was correlated with size of tumor. Upon surgical tumor removal, chemotaxis fell to normal levels unless metastasis had occurred, in which case, the extent of chemotaxis was correlated with the volume of the metastasis. Increased chemotaxis was seen in relation to the growth of a mammary adenocarcinoma as well as that of a chemically induced fibrosarcoma. The major chemotactant in serum was shown to be complement derived, and sera from tumor-bearing and normal animals were equally effective. The presence of a tumor resulted in an increase in the percentage of polymorphonuclear cells in the bone marrow. The numbers of cells which migrated were independent of the cellular composition of the bone marrow in normal mice. In contrast, a negative correlation was found between the percentage of lymphocytes present and the number of bone marrow cells which migrated toward activated serum when the cells originated in a tumor-bearing mouse. The data suggested the increased chemotaxis was a property of the cells rather than the soluble substances in the serum.

Adenocarcinoma↗
PubMed1998

Avascular necrosis of the femoral head: MR imaging with radiological and histological correlation.

OBJECTIVE: To assess the value of MR in the diagnosis of avascular necrosis (AVN) of the femoral head. METHODS: MR images in 34 consecutive patients (26 men and 8 women) with AVN (57 hips) were reviewed. All lesions were confirmed by radiographic, radionuclide, computed tomographic, and/or histologic examination. Eleven specimens were obtained after total replacement of the hip. Four hips underwent biopsy. All MR images were obtained using a 0.35 T superconductive imaging unit with SE sequence. Specimens were cut coronally into 5 mm thick section and radiographs were obtained. RESULTS: There were four types of MR patterns of AVN. Type one appeared liner or patchy low signal area in the superoanterior portion of the femoral head. In type two, a band or ring of low signal intensity was found surrounding a central area of high signal intensity on T1WI and intermediate signal intensity on T2WI. The low signal band or ring consisted of thickened trabecular bone, mesenchymal and fibrous tissue, and amorphous acidophilic cellular debris. The central zones within the ring were composed of necrotic bone and marrow that had not been reached by the repair process. In type three, the focal subchondral region showed intermediate signal intensity on T1WI and high signal on T2WI surrounded by a low signal ring. The low signal ring consisted of thickened trabecular bone and little mesenchymal tissue. The central area was composed of mesenchymal tissue rich in capillaries and cystic necrotic zones. In type four, the signal intensity of femoral head was inhomogeneous on both T1WI and T2WI. There were low signal bands in the femoral neck surrounding the necrotic zone. Only limited areas of some lesions had signal intensity isointense with fat on T1WI and T2WI. The inhomogeneous area of low signal intensity consisted of a mixture of necrotic bone and marrow, amorphous cellular debris. The first type of MR pattern corresponded to the early stage of radiograph, and the third type of MR pattern to stage 5. The second and fourth type of MR patterns correlated less with the radiographic stage. CONCLUSIONS: MR imaging plays an important role in the diagnosis of AVN of femoral head especially in the early detection of AVN. The MR patterns of AVN is not correlated with radiographic stages exactly.

Female↗
PubMed1995

Benzo[a]pyrene-induced alterations in total immune cell number and cell-surface antigen expression in the thymus, spleen and bone marrow of B6C3F1 mice.

Although considerable evidence suggests that carcinogenic polycyclic aromatic hydrocarbons are immunosuppressive compounds, limited information is available regarding precise effects of these agents on immune cells. In the present report, the effect of subchronic exposure to benzo[a]pyrene (B[a]P) on immune cells in bone marrow, thymus and spleen of B6C3F1 mice was investigated. B[a]P treatment was found to reduce thymic cellularity and also to significantly alter normal thymocyte differentiation, as indicated by expression of CD4 and CD8 cell-surface antigens. Exposure to B[a]P also reduced cellularity of the bone marrow, including decreased percentage and absolute number of CD45R+ B-lineage lymphocytes. Further, B[a]P treatment dramatically increased the percentage of CD44hi cells in bone marrow, while proportionately reducing CD44lo cells. These results may indicate CD44lo bone marrow cells, including prolymphocytic cells, represent sensitive targets of B[a]P. The spleens of treated mice were found deficient in both Thy 1.2+ T lymphocytes and CD45R+ B lymphocytes, effects that correlate well with the chemical-induced alterations observed in thymus and bone marrow, respectively.

Animals↗
PubMed2001

Immune response to perforated and partially demineralized bone allografts.

Immune responses have been shown to be involved in the pathogenesis of clinical complications of cortical bone allografts. In an attempt to reduce the immunogenicity of these allografts, we evaluated cortical bone allografts modified by laser perforation and partial demineralization transplanted orthotopically into sheep tibiae. The recipient animals were divided into three groups, of eight animals each, according to the type of cortical allograft that was transplanted: group 1, no treatment (control); group 2, demineralization only; and group 3, laser perforation and partial demineralization. All animals were tissue-typed by biochemical definition of MHC class I molecules, using unidimensional isoelectric focusing and Western blotting. Mismatches of donors and recipients were assessed by testing samples of each donor and recipient pair in parallel and by comparing their individual bands. Donor-specific alloantibodies were detected by a similar technique, using an enzyme-linked immunosorbent assay (ELISA) format. Negative controls were included in all tests. All grafts were poorly immunogenic, whether they were untreated, processed by partial demineralization, or processed by both laser perforation and partial demineralization. Only two recipient animals showed a transient, antibody-mediated donor-specific immune response. One of these animals had received a control allograft, whereas the other animal had received a laser-perforated and partially demineralized bone allograft. All of the grafts in this study, including control grafts, were stripped of soft tissues and their bone marrow was removed; cellular sources of alloantibody stimulation may have been eliminated by these processes. The results of this study suggest that immune responses to bone allografts may be reduced by removing the bone marrow and adjacent soft tissues. The processing of cortical bone allografts by laser perforation and partial demineralization appeared to have little effect on immune responses.

Animals↗
PubMed1994

Antisense oligonucleotide inhibition of acetylcholinesterase gene expression induces progenitor cell expansion and suppresses hematopoietic apoptosis ex vivo.

To examine the role of acetylcholinesterase (EC 3.1.1.7) in hematopoietic cell proliferation and differentiation, we administered a 15-mer phosphorothioate oligonucleotide, antisense to the corresponding ACHE gene (AS-ACHE), to primary mouse bone marrow cultures. Within 2 hr of AS-ACHE addition to the culture, ACHE mRNA levels dropped by approximately 90%, as compared with those in cells treated with the "sense" oligomer, S-ACHE. Four days after AS-ACHE treatment, ACHE mRNA increased to levels 10-fold higher than in S-ACHE cultures or in fresh bone marrow. At this later time point, differential PCR display revealed significant differences between cellular mRNA transcripts in bone marrow and those in AS-ACHE- or S-ACHE-treated cultures. These oligonucleotide-triggered effects underlay considerable alterations at the cellular level: AS-ACHE but not S-ACHE increased cell counts, reflecting enhanced proliferation. In the presence of erythropoietin it also enhanced colony counts, reflecting expansion of progenitors. AS-ACHE further suppressed apoptosis-related fragmentation of cellular DNA in the progeny cells, and it diverted hematopoiesis toward production of primitive blasts and macrophages in a dose-dependent manner promoted by erythropoietin. These findings suggest that the hematopoietic role of acetylcholinesterase, anticipated to be inverse to the observed antisense effects, is to reduce proliferation of the multipotent stem cells committed to erythropoiesis and megakaryocytopoiesis and macrophage production and to promote apoptosis in their progeny. Moreover, these findings may explain the tumorigenic association of perturbations in ACHE gene expression with leukemia.

Acetylcholinesterase↗
PubMed2004

Cellular niches controlling B lymphocyte behavior within bone marrow during development.

In bone marrow, hematopoiesis is thought to depend on special microenvironments known as niches that maintain blood cells. However, the identity of niches and interaction of blood cells with niches remain poorly understood. Here we identify stage-specific cellular niches for B lymphopoiesis. The earliest precursors, pre-pro-B cells and end-stage B cells, plasma cells require CXC chemokine ligand (CXCL)12. CXCL12-expressing cells are a small population of stromal cells, scattered throughout bone marrow and located some distance from the cells expressing interleukin (IL)-7. Multipotent hematopoietic progenitors are attached to the processes of CXCL12-expressing cells and pre-pro-B cells adjoin their cell bodies. Maturer pro-B cells that require IL-7 have moved away and adjoin the IL-7-expressing cells. Plasma cells again seed CXCL12-expressing cells. We demonstrate the B lymphocyte characteristic location and movement between specific niches within bone marrow during development and suggest that CXCL12 maintains the cells in the niche.

Animals↗
PubMed1986

Plasma membrane and intracellular expression of globotetraosylceramide (globoside) in mouse bone marrow-derived mast cells.

The cellular localization of globotetraosylceramide (globoside), one of the predominant neutral glycosphingolipids of mouse interleukin 3-dependent, bone marrow culture-derived mast cells (BMMC), has been determined by immunologic and chemical methods. Although less than 10% of BMMC expressed globoside on their surface, as assessed by cytofluorographic analysis of the binding of a mouse monoclonal IgM anti-globoside antibody, treatment of BMMC with nonactivating doses of pronase, trypsin, or neuraminidase increased the percentage of BMMC binding anti-globoside antibody by an average of six, three, or sixfold respectively. That most BMMC had globoside on their plasma membrane was confirmed by the surface radiolabeling of globoside with galactose oxidase and sodium borotritide, as detected by autoradiography of thin layer chromatograms of the extracted neutral glycosphingolipids. Thus, BMMC expressed globoside on their plasma membrane, but accessibility of a large probe such as IgM antibody to the glycosphingolipid was impeded by surrounding surface molecules. All BMMC bound anti-globoside antibody intracellularly, as assessed by indirect immunofluorescence staining and fluorescence microscopy on acetone-permeabilized cells, and the pattern of staining suggested that globoside was associated with the secretory granules of BMMC. Immunologic activation of BMMC resulted in a fivefold increase in the surface expression of globoside, as detected by cytofluorographic analysis of the binding of monoclonal anti-globoside antibody. The findings suggest that activation of BMMC causes a reorganization of the plasma membrane such that globoside is more exposed or that activation is accompanied by movement of globoside from internal membranes to the plasma membrane. The increased expression of globoside is a novel marker of the activated mouse BMMC.

Animals↗
PubMed1975

Megakaryocytes in agar cultures of mouse bone marrow.

Cytologic and immunofluorescent data demonstrate that cells morphologically resembling megakaryocytes appear in thin layer agar cultures of cellular fractions of mouse bone marrow and increase in number from zero to a maximum of approxiamately 60 per culture on day 6. It would appear that these "candidate" megakaryocytes are derived from a morphologically unidentified precursor(s) since they are not present in the original cell suspension cultured but begin to appear 24 hours later. Similarities between the ultrastructure of "candidate" megakaryocytes and that of femoral marrow megakaryocytes support morphological similarities at the light microscopic level. Pretreatment of mice with either vinblastine and nitrogen mustard or antiplatelet serum has no effect on the number of "candidate" megakaryocytes appearing in cultures of their marrow. Preliminary data suggest that the rate of appearance of these cells in culture is responsive to serum from thrombocytopenic donors.

Agar↗
PubMed2001

Marrow-derived cells populate scaffolds composed of xenogeneic extracellular matrix.

INTRODUCTION: The source of cells that participate in wound repair directly affects outcome. The extracellular matrix (ECM) and other acellular biomaterials have been used as therapeutic scaffolds for cell attachment and proliferation and as templates for tissue repair. The ECM consists of structural and functional proteins that influence cell attachment, gene expression patterns, and the differentiation of cells. OBJECTIVE: The objective of this study was to determine if the composition of acellular matrix scaffolds affects the recruitment of bone marrow-derived cellular elements that populate the scaffolds in vivo. METHODS: Scaffolds composed of porcine tissue ECM, purified Type I collagen, poly(L)lactic coglycolic acid (PLGA), or a mixture of porcine ECM and PLGA were implanted into subcutaneous pouches on the dorsum of mice. The origin of cells that populated the matrices was determined by first performing bone marrow transplantation to convert the marrow of glucose phosphate isomerase 1b (Gpi-1(b)) mice to cells expressing glucose phosphate isomerase 1a (Gpi-1(a)). RESULTS: A significant increase in Gpi-1(a) expressing cells was present in sites implanted with the porcine ECM compared to sites implanted with either Type I collagen or PLGA. Use of recipient mice transplanted with marrow cells that expressed beta-galactosidase confirmed that the majority of cells that populated and remodeled the naturally occurring porcine ECM were marrow derived. Addition of porcine ECM to the PLGA scaffold caused a significant increase in the number of marrow-derived cells that became part of the remodeled implant site. CONCLUSION: The composition of bioscaffolds affects the cellular recruitment pattern during tissue repair. ECM scaffolds facilitate the recruitment of marrow-derived cells into sites of remodeling.

Animals↗