Influence of Epinastine Hydrochloride, an -Receptor Antagonist, on the Function of Mite Allergen-Pulsed Murine Bone Marrow-Derived Dendritic Cells In Vitro and In Vivo

There is established concept that dendritic cells (DCs) play essential roles in the development of allergic immune responses. However, the influence of receptor antagonists on DC functions is not well defined. The aim of the present study was to examine the effect of epinastine hydrochloride (EP), the most notable histamine receptor antagonists in Japan, onDermatophagoides farinae (Der f)-pulsed mouse bone marrow-derived DCs in vitro and in vivo. EP at more than 25 ng/mL could significantly inhibit the production of IL-6, TNF- and IL-10 fromDer f-pulsed DCs, which was increased byDer fchallenge in vitro. On the other hand, EP increased the ability ofDer f-pulsed DCs to produce IL-12. Intranasal instillation ofDer f-pulsed DCs resulted in nasal eosinophilia associated with a significant increase in IL-5 levels in nasal lavage fluids.Der f-pulsed and EP-treated DCs significantly inhibited nasal eosinophila and reduced IL-5. These results indicate that EP inhibits the development of Th2 immune responses through the modulation of DC functions and results in favorable modification of clinical status of allergic diseases.

Download Full-text

Expression of human adenosine deaminase in murine hematopoietic cells

Molecular and Cellular Biology ◽

10.1128/mcb.8.12.5116-5125.1988 ◽

1988 ◽

Vol 8 (12) ◽

pp. 5116-5125

Author(s):

J W Belmont ◽

G R MacGregor ◽

K Wager-Smith ◽

F A Fletcher ◽

K A Moore ◽

...

Keyword(s):

Bone Marrow ◽

Adenosine Deaminase ◽

High Titer ◽

Virus Production ◽

Marrow Transplant ◽

Mouse Bone Marrow ◽

Regulation Of Expression ◽

Murine Bone Marrow

Multiple replication-defective retrovirus vectors were tested for their ability to transfer and express human adenosine deaminase in vitro and in vivo in a mouse bone marrow transplantation model. High-titer virus production was obtained from vectors by using both a retrovirus long terminal repeat promoter and internal transcriptional units with human c-fos and herpes virus thymidine kinase promoters. After infection of primary murine bone marrow with one of these vectors, human adenosine deaminase was detected in 60 to 85% of spleen colony-forming units and in the blood of 14 of 14 syngeneic marrow transplant recipients. This system offers the opportunity to assess methods for increasing efficiency of gene transfer, for regulation of expression of foreign genes in hematopoietic progenitors, and for long-term measurement of the stability of expression in these cells.

Download Full-text

Pasteurella multocida Toxin Activates Human Monocyte-Derived and Murine Bone Marrow-Derived Dendritic Cells In Vitro but Suppresses Antibody Production In Vivo

Infection and Immunity ◽

10.1128/iai.73.1.413-421.2005 ◽

2005 ◽

Vol 73 (1) ◽

pp. 413-421 ◽

Cited By ~ 22

Author(s):

Kenneth C. Bagley ◽

Sayed F. Abdelwahab ◽

Robert G. Tuskan ◽

George K. Lewis

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

Phospholipase C ◽

Cholera Toxin ◽

Pasteurella Multocida ◽

Human Monocyte ◽

Mouse Bone Marrow ◽

Dependent Manner

ABSTRACT Pasteurella multocida toxin (PMT) is a potent mitogen for fibroblasts and osteoblastic cells. PMT activates phospholipase C-β through Gqα, and the activation of this pathway is responsible for its mitogenic activity. Here, we investigated the effects of PMT on human monocyte-derived dendritic cells (MDDC) in vitro and show a novel activity for PMT. In this regard, PMT activates MDDC to mature in a dose-dependent manner through the activation of phospholipase C and subsequent mobilization of calcium. This activation was accompanied by enhanced stimulation of naïve alloreactive T cells and dominant inhibition of interleukin-12 production in the presence of saturating concentrations of lipopolysaccharide. Surprisingly, although PMT mimics the activating effects of cholera toxin on human MDDC and mouse bone marrow-derived dendritic cells, we found that PMT is not a mucosal adjuvant and that it suppresses the adjuvant effects of cholera toxin in mice. Together, these results indicate discordant effects for PMT in vitro compared to those in vivo.

Download Full-text

Expression of human adenosine deaminase in murine hematopoietic cells.

Molecular and Cellular Biology ◽

10.1128/mcb.8.12.5116 ◽

1988 ◽

Vol 8 (12) ◽

pp. 5116-5125 ◽

Cited By ~ 70

Author(s):

J W Belmont ◽

G R MacGregor ◽

K Wager-Smith ◽

F A Fletcher ◽

K A Moore ◽

...

Keyword(s):

Bone Marrow ◽

Adenosine Deaminase ◽

High Titer ◽

Virus Production ◽

Marrow Transplant ◽

Mouse Bone Marrow ◽

Regulation Of Expression ◽

Murine Bone Marrow

Download Full-text

Chronic Myelogenous Leukemia Cells Contribute to the Stromal Myofibroblasts in Leukemic NOD/SCID MouseIn Vivo

Journal of Oncology ◽

10.1155/2012/901783 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Ryosuke Shirasaki ◽

Haruko Tashiro ◽

Yoko Oka ◽

Takuji Matsuo ◽

Tadashi Yamamoto ◽

...

Keyword(s):

Bone Marrow ◽

Chronic Myelogenous Leukemia ◽

Mononuclear Cells ◽

Severe Combined Immunodeficiency ◽

Myelogenous Leukemia ◽

Mouse Bone Marrow ◽

Murine Bone Marrow ◽

Endothelial Growth Factor

We recently reported that chronic myelogenous leukemia (CML) cells converted into myofibroblasts to create a microenvironment for proliferation of CML cellsin vitro. To analyze a biological contribution of CML-derived myofibroblastsin vivo, we observed the characters of leukemic nonobese diabetes/severe combined immunodeficiency (NOD/SCID) mouse. Bone marrow nonadherent mononuclear cells as well as human CD45-positive cells obtained from CML patients were injected to the irradiated NOD/SCID mice. When the chimericBCR-ABLtranscript was demonstrated in blood, human CML cells were detected in NOD/SCID murine bone marrow. And CML-derived myofibroblasts composed with the bone marrow-stroma, which produced significant amounts of human vascular endothelial growth factor A. When the parental CML cells were cultured with myofibroblasts separated from CML cell-engrafted NOD/SCID murine bone marrow, CML cells proliferated significantly. These observations indicate that CML cells make an adequate microenvironment for their own proliferationin vivo.

Download Full-text

Synergistic combination of murine bone marrow-derived dendritic cells loaded ex vivo with whole tumor lysate and systemic chemotherapy mediates antitumor immune responses in vivo

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2017.06.046 ◽

2017 ◽

Vol 93 ◽

pp. 286-295

Author(s):

Mohamed L. Salem ◽

Mohamed Nassef ◽

Soha Gomaa ◽

Ibrahim Essa

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

Immune Responses ◽

Systemic Chemotherapy ◽

Ex Vivo ◽

Tumor Lysate ◽

Murine Bone Marrow ◽

Synergistic Combination

Download Full-text

Characterization of a 5-fluorouracil-enriched osteoprogenitor population of the murine bone marrow

Blood ◽

10.1182/blood.v82.12.3580.bloodjournal82123580 ◽

1993 ◽

Vol 82 (12) ◽

pp. 3580-3591

Author(s):

N Falla ◽

Vlasselaer Van ◽

J Bierkens ◽

B Borremans ◽

G Schoeters ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Cells ◽

Collagen Matrix ◽

Collagen Type I ◽

Nodule Formation ◽

Mouse Bone Marrow ◽

Type I ◽

Murine Bone Marrow

In the presence of beta-glycerophosphate and vitamin C, cultures of normal mouse bone marrow cells form three-dimensional structures that stain positive with the Von Kossa technique and express alkaline phosphatase (ALP), collagen type I, and osteocalcin. Little is known about the characteristics and frequency of the cells that contribute to this phenomenon. Most likely, mature osteoblastic cells do not contribute to the nodule formation because no osteocalcin expressing cells are detected in the flushed marrow by in situ hybridization. Limiting dilution analysis shows that, in normal bone marrow, 1 of 2.2 x 10(5) cells has the potency to form a bone nodule and to express ALP, collagen, and osteocalcin in a temporal fashion. Upon in vivo treatment with 5-fluorouracil (5-FU), this frequency increases 12-fold, eg, 1 in 1.75 x 10(4) cells shows osteogenic activity. In comparison, fibroblast colony forming cells occur at a frequency of 1 of 2.5 x 10(4) or 1 of 5 x 10(3) plated cells in normal or 5-FU-treated marrow, respectively. Using density centrifugation, the majority of the osteoprogenitor cells in 5-FU marrow are found in the low-density (1.066 to 1.067 g/mL) fractions. In addition, these cells bind to nylon wool but not to plastic and aggregate in the presence of wheat germ agglutinin and soybean agglutinin. Scanning and transmission electron microscopy shows that the bone nodules in 5-FU marrow cultures are composed of fibroblastoid cells embedded in a mineralized collagen matrix. In conclusion, our results show that a quiescent cell population in the murine bone marrow with fibroblastoid characteristics contributes to the formation of bone-like nodules in vitro.

Download Full-text

PARP-1 inhibition prevents CNS migration of dendritic cells during EAE, suppressing the encephalitogenic response and relapse severity

Multiple Sclerosis Journal ◽

10.1177/1352458511399113 ◽

2011 ◽

Vol 17 (7) ◽

pp. 794-807 ◽

Cited By ~ 26

Author(s):

Leonardo Cavone ◽

Alessandra Aldinucci ◽

Clara Ballerini ◽

Tiziana Biagioli ◽

Flavio Moroni ◽

...

Keyword(s):

Bone Marrow ◽

Dendritic Cells ◽

Molecular Mechanisms ◽

Neurological Impairment ◽

Mouse Bone Marrow ◽

In Vivo Models ◽

In Vitro Techniques ◽

Parp 1

Background: Pharmacological inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1) are currently evaluated in clinical trials for various malignancies but, interestingly, also proved of remarkable efficacy in preclinical models of autoimmune disorders including experimental autoimmune encephalomyelitis (EAE). Objectives: The objectives of the study were to determine molecular mechanisms underlying suppression of the encephalitogenic response by these drugs; likewise, whether clinically-relevant post-treatment paradigms with PARP-1 inhibitors could prevent EAE relapses. Methods: Adopted both in vitro techniques (bone marrow-derived cultured DC) as well as in vivo models of chronic or relapsing–remitting (RR) EAE. Results: We report that two structurally unrelated PARP-1 inhibitors negatively regulated NFκB activation, as well as maturation, cytokine production and APC function of cultured mouse bone marrow-derived dendritic cells (DCs). PARP-1 inhibitors also reduced the number and APC function of DCs migrating in the draining lymph nodes of ovalbumin-immunized mice. In C57Bl mice with chronic EAE or SJL mice with RR EAE, pharmacological inhibition of PARP-1 reduced CNS DC migration and demyelination as well as neurological impairment to an extent similar to that achieved with the potent immunosuppressant cyclosporine A. Remarkably, PARP-1 inhibitors injected after the first phase of disease reduced relapse incidence and severity, as well as the spinal cord number of autoreactive Th17 cells. Under this clinically-relevant treatment paradigm, PARP inhibitors also suppressed epitope spreading of the encephalitogenic response. Conclusions: Overall, data underscore the potential relevance of PARP-1 inhibitors to MS therapy and suppression of autoimmunity.

Download Full-text

Characterization of a 5-fluorouracil-enriched osteoprogenitor population of the murine bone marrow

Blood ◽

10.1182/blood.v82.12.3580.3580 ◽

1993 ◽

Vol 82 (12) ◽

pp. 3580-3591 ◽

Cited By ~ 68

Author(s):

N Falla ◽

Vlasselaer Van ◽

J Bierkens ◽

B Borremans ◽

G Schoeters ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Cells ◽

Collagen Matrix ◽

Collagen Type I ◽

Nodule Formation ◽

Mouse Bone Marrow ◽

Type I ◽

Murine Bone Marrow

Abstract In the presence of beta-glycerophosphate and vitamin C, cultures of normal mouse bone marrow cells form three-dimensional structures that stain positive with the Von Kossa technique and express alkaline phosphatase (ALP), collagen type I, and osteocalcin. Little is known about the characteristics and frequency of the cells that contribute to this phenomenon. Most likely, mature osteoblastic cells do not contribute to the nodule formation because no osteocalcin expressing cells are detected in the flushed marrow by in situ hybridization. Limiting dilution analysis shows that, in normal bone marrow, 1 of 2.2 x 10(5) cells has the potency to form a bone nodule and to express ALP, collagen, and osteocalcin in a temporal fashion. Upon in vivo treatment with 5-fluorouracil (5-FU), this frequency increases 12-fold, eg, 1 in 1.75 x 10(4) cells shows osteogenic activity. In comparison, fibroblast colony forming cells occur at a frequency of 1 of 2.5 x 10(4) or 1 of 5 x 10(3) plated cells in normal or 5-FU-treated marrow, respectively. Using density centrifugation, the majority of the osteoprogenitor cells in 5-FU marrow are found in the low-density (1.066 to 1.067 g/mL) fractions. In addition, these cells bind to nylon wool but not to plastic and aggregate in the presence of wheat germ agglutinin and soybean agglutinin. Scanning and transmission electron microscopy shows that the bone nodules in 5-FU marrow cultures are composed of fibroblastoid cells embedded in a mineralized collagen matrix. In conclusion, our results show that a quiescent cell population in the murine bone marrow with fibroblastoid characteristics contributes to the formation of bone-like nodules in vitro.

Download Full-text

Fate of Mycobacterium tuberculosis within Murine Dendritic Cells

Infection and Immunity ◽

10.1128/iai.69.2.800-809.2001 ◽

2001 ◽

Vol 69 (2) ◽

pp. 800-809 ◽

Cited By ~ 145

Author(s):

Kendra A. Bodnar ◽

Natalya V. Serbina ◽

JoAnne L. Flynn

Keyword(s):

Nitric Oxide ◽

Bone Marrow ◽

Immune Response ◽

Dendritic Cells ◽

Mycobacterium Tuberculosis ◽

Immune Responses ◽

Intracellular Bacteria ◽

Murine Bone Marrow ◽

Oxide Synthase

ABSTRACT The interaction of microbes with dendritic cells (DCs) is likely to have an enormous impact on the initiation of the immune response against a pathogen. In this study, we compared the interaction ofMycobacterium tuberculosis with murine bone marrow-derived DCs and macrophages (Mφ) in vitro. M. tuberculosis grew equally well within nonactivated DCs and Mφ. Activation of DCs and Mφ with gamma interferon and lipopolysaccharide inhibited the growth of the intracellular bacteria in a nitric oxide synthase-dependent fashion. However, while this activation enabled Mφ to kill the intracellular bacteria, the M. tuberculosis bacilli within activated DCs were not killed. Thus, DCs could restrict the growth of the intracellular mycobacteria but were less efficient than Mφ at eliminating the infection. These results may have implications for priming immune responses to M. tuberculosis. In addition, they suggest that DCs may serve as a reservoir for M. tuberculosis in tissues, including the lymph nodes and lungs.

Download Full-text

Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow

Journal of Experimental Medicine ◽

10.1084/jem.20091046 ◽

2009 ◽

Vol 206 (11) ◽

pp. 2483-2496 ◽

Cited By ~ 505

Author(s):

Satoru Morikawa ◽

Yo Mabuchi ◽

Yoshiaki Kubota ◽

Yasuo Nagai ◽

Kunimichi Niibe ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Mouse Bone Marrow ◽

Quiescent State ◽

Murine Bone Marrow ◽

Multipotent Mesenchymal Stem Cells ◽

Hematopoietic Niche

Mesenchymal stem cells (MSCs) are defined as cells that undergo sustained in vitro growth and can give rise to multiple mesenchymal lineages. Because MSCs have only been isolated from tissue in culture, the equivalent cells have not been identified in vivo and little is known about their physiological roles or even their exact tissue location. In this study, we used phenotypic, morphological, and functional criteria to identify and prospectively isolate a subset of MSCs (PDGFRα+Sca-1+CD45−TER119−) from adult mouse bone marrow. Individual MSCs generated colonies at a high frequency and could differentiate into hematopoietic niche cells, osteoblasts, and adipocytes after in vivo transplantation. Naive MSCs resided in the perivascular region in a quiescent state. This study provides the useful method needed to identify MSCs as defined in vivo entities.

Download Full-text