scholarly journals AMD3100 ameliorates cigarette smoke-induced emphysema-like manifestations in mice

2018 ◽  
Vol 315 (3) ◽  
pp. L382-L386 ◽  
Author(s):  
Daria Barwinska ◽  
Houssam Oueini ◽  
Christophe Poirier ◽  
Marjorie E. Albrecht ◽  
Natalia V. Bogatcheva ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cigarette Smoke ◽  
Inflammatory Cell ◽  
Therapeutic Benefit ◽  
Static Compliance ◽  
Cell Counts ◽  
Stromal Cell Derived Factor ◽  
And Function ◽  
Potential Therapeutic Benefit ◽  
Marked Suppression

We have shown that cigarette smoke (CS)-induced pulmonary emphysema-like manifestations are preceded by marked suppression of the number and function of bone marrow hematopoietic progenitor cells (HPCs). To investigate whether a limited availability of HPCs may contribute to CS-induced lung injury, we used a Food and Drug Administration-approved antagonist of the interactions of stromal cell-derived factor 1 (SDF-1) with its chemokine receptor CXCR4 to promote intermittent HPC mobilization and tested its ability to limit emphysema-like injury following chronic CS. We administered AMD3100 (5mg/kg) to mice during a chronic CS exposure protocol of up to 24 wk. AMD3100 treatment did not affect either lung SDF-1 levels, which were reduced by CS, or lung inflammatory cell counts. However, AMD3100 markedly improved CS-induced bone marrow HPC suppression and significantly ameliorated emphysema-like end points, such as alveolar airspace size, lung volumes, and lung static compliance. These results suggest that antagonism of SDF-1 binding to CXCR4 is associated with protection of both bone marrow and lungs during chronic CS exposure, thus encouraging future studies of potential therapeutic benefit of AMD3100 in emphysema.

scholarly journals Galgeun-tang Attenuates Cigarette Smoke and Lipopolysaccharide Induced Pulmonary Inflammation via IκBα/NF-κB Signaling

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2489 ◽  
Author(s):  
Na-Rae Shin ◽  
Chul Kim ◽  
Chang-Seob Seo ◽  
Je-Won Ko ◽  
Young-Kwon Cho ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Inflammatory Cell ◽  
Pulmonary Inflammation ◽  
Water Extract ◽  
Lavage Fluid ◽  
Chronic Obstructive ◽  
Necrosis Factor Alpha ◽  
Obstructive Pulmonary Disease ◽  
Cell Counts ◽  
Oxide Synthase

Galgeun-tang water extract (GGWE) is used to treat various diseases such as the common cold, eczema and asthma in China and Korea. In this study, we investigated the anti-inflammatory effect of GGWE using a cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced induced pulmonary inflammation mouse model. The mice were exposed to CS for a total of seven days (eight cigarettes per day for 1 h) and LPS was administered intranasally to mice on day 4. GGWE was administered by oral gavage at doses of 50 mg/kg or 100 mg/kg 1 h before exposure to CS. GGWE decreased inflammatory cell counts, and expression of inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) in bronchoalveolar lavage fluid (BALF) from mice exposed to CS and LPS. GGWE reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the phosphorylation of inhibitor of kappa-B subunit alpha (IκBα) and nuclear factor kappa-B (NF-κB) in CS- and LPS-exposed mice. Histological examinations revealed that GGWE suppressed inflammatory cell infiltration into lung tissue compared to untreated CS- and LPS-exposed mice. In conclusion, GGWE effectively suppressed CS- and LPS-induced pulmonary inflammation. Our results indicate that GGWE may be used as a protective drug to control pulmonary inflammation diseases such as chronic obstructive pulmonary disease.

scholarly journals Glioblastoma-synthesized G-CSF and GM-CSF contribute to growth and immunosuppression: Potential therapeutic benefit from dapsone, fenofibrate, and ribavirin

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769979 ◽  
Author(s):  
Richard E Kast ◽  
Quentin A Hill ◽  
Didier Wion ◽  
Håkan Mellstedt ◽  
Daniele Focosi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Antiviral Drug ◽  
Therapeutic Benefit ◽  
Lipid Lowering ◽  
Common Finding ◽  
European Medicines Agency ◽  
Gm Csf ◽  
Growth Promoting ◽  
The Brain ◽  
Potential Therapeutic Benefit

Increased ratio of circulating neutrophils to lymphocytes is a common finding in glioblastoma and other cancers. Data reviewed establish that any damage to brain tissue tends to cause an increase in G-CSF and/or GM-CSF (G(M)-CSF) synthesized by the brain. Glioblastoma cells themselves also synthesize G(M)-CSF. G(M)-CSF synthesized by brain due to damage by a growing tumor and by the tumor itself stimulates bone marrow to shift hematopoiesis toward granulocytic lineages away from lymphocytic lineages. This shift is immunosuppressive and generates the relative lymphopenia characteristic of glioblastoma. Any trauma to brain—be it blunt, sharp, ischemic, infectious, cytotoxic, tumor encroachment, or radiation—increases brain synthesis of G(M)-CSF. G(M)-CSF are growth and motility enhancing factors for glioblastomas. High levels of G(M)-CSF contribute to the characteristic neutrophilia and lymphopenia of glioblastoma. Hematopoietic bone marrow becomes entrained with, directed by, and contributes to glioblastoma pathology. The antibiotic dapsone, the lipid-lowering agent fenofibrate, and the antiviral drug ribavirin are Food and Drug Administration– and European Medicines Agency–approved medicines that have potential to lower synthesis or effects of G(M)-CSF and thus deprive a glioblastoma of some of the growth promoting contributions of bone marrow and G(M)-CSF.

SDF-1 Responsiveness Does Not Correlate With CXCR4 Expression Levels of Developing Human Bone Marrow B Cells

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 2990-2998 ◽  
Author(s):  
Marek Honczarenko ◽  
Raymond S. Douglas ◽  
Clarissa Mathias ◽  
Benhur Lee ◽  
Mariusz Z. Ratajczak ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Cxcr4 Expression ◽  
B Lymphopoiesis ◽  
Cell Stage ◽  
Immature B Cells ◽  
Stromal Cell Derived Factor ◽  
And Migration ◽  
And Function

Abstract Chemokines and their receptors are broadly expressed in different tissues and are involved in diverse biologic processes. Gene inactivation studies have shown that both stromal cell derived factor-1 (SDF-1) and chemokine receptor 4 (CXCR4) are essential for B lymphopoiesis. However, it is not yet clear by which mechanisms B lymphopoiesis is affected. In the present study, we have examined CXCR4 expression and function on primary B cells representing sequential stages of development (eg, pro-B, pre-B, immature, and mature B cells) in fetal and adult bone marrow. The expression of CXCR4 was observed to be sinusoidal. Expression was highest on pre-B cells, decreased as cells developed into immature B cells, and then increased again upon transition to the mature B-cell stage. The corresponding ligand SDF-1 was shown to trigger vigorous cell signaling and migration responses, which are restricted to early lineage B cells. The responsiveness to SDF-1 was markedly decreased for immature and mature B cells despite relatively high levels of CXCR4 expression. Thus, the diminished responsiveness to SDF-1 by more mature B cells was determined to be disproportionate to the level of CXCR4 expression. These findings raise the possibility that CXCR4 function is differentially controlled during B lymphopoiesis and may be relevant to the compartmentalization of B-cell precursors in the bone marrow.

Functional CXCR4 Expressing Microparticles and SDF-1 Correlate with Circulating AML Cell Counts.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4375-4375
Author(s):  
Alexander Kalinkovich ◽  
Sigal Tavor ◽  
Abraham Avigdor ◽  
Joy Kahn ◽  
Alexander Brill ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Proteolytic Enzymes ◽  
Cxcr4 Antagonist ◽  
Human Cd34 ◽  
Cell Counts ◽  
Normal Individuals ◽  
Bone Marrow Plasma ◽  
Stromal Cell Derived Factor

Abstract Stromal cell-derived factor-1 (SDF-1/CXCL12) and its receptor CXCR4 are implicated in the pathogenesis and prognosis of AML. Cellular microparticles (MPs), the submicron vesicles shed from the plasma membrane of various circulating cells, are associated with numerous human disorders. In the present study, we studied the putative relationships between CXCR4/SDF-1 axis and MPs in AML. We detected CXCR4 expressing MPs (CXCR4+MPs) in the peripheral blood and bone marrow plasma samples of normal donors (n=24) and newly diagnosed adult AML patients (n=26). The majority of CXCR4+MPs in AML patients were CD45+ whereas in normal individuals they were mostly CD41+. In samples from AML patients, the levels of CXCR4+MPs and total SDF-1 were significantly elevated as compared to normal individuals. Importantly, we found a strong correlation between the levels of CXCR4+MP and white blood cell (WBC) counts in the peripheral blood and bone marrow plasma obtained from the AML patients. Of interest, functional, non-cleaved SDF-1 levels were reduced in these patients compared to normal individuals, and also strongly correlated with the WBC counts. Furthermore, our data indicate N-terminal truncation of the CXCR4 molecule in the MPs of AML patients. This was found also in MPs obtained from the conditioned media of normal human CD34+ progenitors lentiviarlly transduced with CXCR4 vector in vitro. Appearance of MPs possessing N-terminally truncated CXCR4 in AML patients is likely to be dependent on proteolytic enzymes, such as elastase, which was elevated. However, MPs isolated from AML patients were capable of transferring functional CXCR4 molecule to the AML-derived HL-60 cells, enhancing their migration to SDF-1 in vitro and increasing their homing to the bone marrow of irradiated NOD/SCID mice. The CXCR4 antagonist AMD3100 reduced the increased migration and homing of MP treated HL-60 cells. Taken together, these findings suggest that functional CXCR4+MPs and SDF-1 are involved in the progression of AML. We propose that their levels are potentially valuable as an additional diagnostic AML parameter. Moreover, our findings suggest also the need for CXCR4- and SDF-1-target therapeutic approaches, clinically relevant in AML in the near future.

SDF-1 Responsiveness Does Not Correlate With CXCR4 Expression Levels of Developing Human Bone Marrow B Cells

Blood ◽  
1999 ◽  
Vol 94 (9) ◽  
pp. 2990-2998 ◽  
Author(s):  
Marek Honczarenko ◽  
Raymond S. Douglas ◽  
Clarissa Mathias ◽  
Benhur Lee ◽  
Mariusz Z. Ratajczak ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Cxcr4 Expression ◽  
B Lymphopoiesis ◽  
Cell Stage ◽  
Immature B Cells ◽  
Stromal Cell Derived Factor ◽  
And Migration ◽  
And Function

Chemokines and their receptors are broadly expressed in different tissues and are involved in diverse biologic processes. Gene inactivation studies have shown that both stromal cell derived factor-1 (SDF-1) and chemokine receptor 4 (CXCR4) are essential for B lymphopoiesis. However, it is not yet clear by which mechanisms B lymphopoiesis is affected. In the present study, we have examined CXCR4 expression and function on primary B cells representing sequential stages of development (eg, pro-B, pre-B, immature, and mature B cells) in fetal and adult bone marrow. The expression of CXCR4 was observed to be sinusoidal. Expression was highest on pre-B cells, decreased as cells developed into immature B cells, and then increased again upon transition to the mature B-cell stage. The corresponding ligand SDF-1 was shown to trigger vigorous cell signaling and migration responses, which are restricted to early lineage B cells. The responsiveness to SDF-1 was markedly decreased for immature and mature B cells despite relatively high levels of CXCR4 expression. Thus, the diminished responsiveness to SDF-1 by more mature B cells was determined to be disproportionate to the level of CXCR4 expression. These findings raise the possibility that CXCR4 function is differentially controlled during B lymphopoiesis and may be relevant to the compartmentalization of B-cell precursors in the bone marrow.

scholarly journals CD4+FOXP3+ T Cells in Rheumatoid Arthritis Bone Marrow Are Partially Impaired

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 549
Author(s):  
Magdalena Massalska ◽  
Anna Radzikowska ◽  
Ewa Kuca-Warnawin ◽  
Magdalena Plebanczyk ◽  
Monika Prochorec-Sobieszek ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Marrow ◽  
T Cells ◽  
Ex Vivo ◽  
Enzyme Linked Immunosorbent Assay ◽  
Suppressive Activity ◽  
Replacement Surgery ◽  
Hip Replacement Surgery ◽  
Stromal Cell Derived Factor ◽  
And Function

There is evolving evidence that dysregulation of immune homeostasis in the bone marrow (BM) adjacent to the inflamed joints is involved in the pathogenesis of. In this study, we are addressing the phenotype and function of regulatory T cells (Tregs) residing in the BM of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). BM and peripheral blood samples were obtained from RA and OA patients undergoing hip replacement surgery. The number and phenotype of Tregs were analyzed by flow cytometry and immunohistochemistry. The function of Tregs was investigated ex vivo, addressing their suppressive activity on effector T cells. [3H]-Thymidine incorporation assay and specific enzyme-linked immunosorbent assay were used for quantification of cell proliferation and pro-inflammatory (TNF, IFN-γ) cytokine release, respectively. Significantly lower numbers of CD4+FOXP3+ T cells were found in the BM of patients with RA compared to control patients with OA. High expression of CD127 (IL-7α receptor) and relatively low expression of CXCR4 (receptor for stromal cell-derived factor CXCL12) are characteristics of the CD4+FOXP3+ cells residing in the BM of RA patients. The BM-resident Tregs of RA patients demonstrated a limited suppressive activity on the investigated immune response. Our results indicate that the reduced number and impaired functional properties of CD4+FOXP3+ T cells present in the BM of RA patients may favor the inflammatory process, which is observed in RA BM.

scholarly journals Cigarette Smoke Suppresses the Surface Expression ofc-kitand FcεRI on Mast Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
M. E. Givi ◽  
B. R. Blokhuis ◽  
C. A. Da Silva ◽  
I. Adcock ◽  
J. Garssen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cells ◽  
Cigarette Smoke ◽  
Inflammatory Cells ◽  
Surface Expression ◽  
Chronic Obstructive ◽  
Independent Manner ◽  
Obstructive Pulmonary Disease ◽  
Short Term Exposure ◽  
And Function

Chronic obstructive pulmonary disease (COPD) is a multicomponent disease characterized by emphysema and/or chronic bronchitis. COPD is mostly associated with cigarette smoking. Cigarette smoke contains over 4,700 chemical compounds, including free radicals and LPS (a Toll-Like Receptor 4 agonist) at concentrations which may contribute to the pathogenesis of diseases like COPD. We have previously shown that short-term exposure to cigarette smoke medium (CSM) can stimulate several inflammatory cells via TLR4 and that CSM reduces the degranulation of bone-marrow-derived mast cells (BMMCs). In the current study, the effect of CSM on mast cells maturation and function was investigated. Coculturing of BMMC with CSM during the development of bone marrow progenitor cells suppressed the granularity and the surface expression ofc-kitand FcεRI receptors. Stimulation with IgE/antigen resulted in decreased degranulation and release of Th1 and Th2 cytokines. The effects of CSM exposure could not be mimicked by the addition of LPS to the culture medium. In conclusion, this study shows that CSM may affect mast cell development and subsequent response to allergic activation in a TLR4-independent manner.

Partial marrow shielding and total-body irradiation

1963 ◽  
Vol 18 (3) ◽  
pp. 629-632 ◽  
Author(s):  
W. D. Noyes ◽  
C. A. Finch ◽  
H. Wasserman ◽  
K. Glickman
Keyword(s):  
Bone Marrow ◽  
Total Body Irradiation ◽  
Marrow Cell ◽  
Red Cell ◽  
Peripheral Cell ◽  
Hemoglobin Synthesis ◽  
Cell Counts ◽  
Total Body ◽  
And Function ◽  
Functional Stress

The effects of shielding one femur on bone marrow morphology and function were studied in rats receiving total-body irradiation. Animals were exposed to 550 r from a Co60 source. Shielding consisted of 100 mm of lead, reducing exposure to one femur to 16 r. Marrow cell counts, radioiron localization in femurs, plasma iron turnover, red cell radioiron utilization, and peripheral cell counts were observed. Phlebotomy in some animals served as a functional stress. There was no observed morphological change in shielded marrow despite marked depopulation of nucleated cells in heavily irradiated marrow. In phlebotomized shielded animals, the rate of hemoglobin synthesis was nearly half that of unirradiated controls although retarded by several days whereas in unshielded animals, hemoglobin synthesis was further delayed and less than a third of control values. Initially the erythropoietic function resides primarily in shielded marrow as evidenced by radioiron localization and marrow cell counts with no evidence of indirect depression. Cellular repopulation appears more rapidly in partially shielded animals and compares favorably with the effectiveness of marrow transfusion. Submitted on December 5, 1962

scholarly journals The composition of cigarette smoke determines inflammatory cell recruitment to the lung in COPD mouse models

2013 ◽  
Vol 126 (3) ◽  
pp. 207-221 ◽  
Author(s):  
Gerrit John ◽  
Katrin Kohse ◽  
Jürgen Orasche ◽  
Ahmed Reda ◽  
Jürgen Schnelle-Kreis ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cigarette Smoke ◽  
Mouse Models ◽  
Inflammatory Cell ◽  
Biological Effects ◽  
Acute Inflammatory Response ◽  
Cell Recruitment ◽  
Gm Csf ◽  
Cell Counts ◽  
Inflammatory Cell Recruitment

COPD (chronic obstructive pulmonary disease) is caused by exposure to toxic gases and particles, most often CS (cigarette smoke), leading to emphysema, chronic bronchitis, mucus production and a subsequent decline in lung function. The disease pathogenesis is related to an abnormal CS-induced inflammatory response of the lungs. Similar to active (mainstream) smoking, second hand (sidestream) smoke exposure severely affects respiratory health. These processes can be studied in vivo in models of CS exposure of mice. We compared the acute inflammatory response of female C57BL/6 mice exposed to two concentrations [250 and 500 mg/m3 TPM (total particulate matter)] of sidestream and mainstream CS for 3 days and interpreted the biological effects based on physico-chemical differences in the gas and particulate phase composition of CS. BAL (bronchoalveolar lavage fluid) was obtained to perform differential cell counts and to measure cytokine release. Lung tissue was used to determine mRNA and protein expression of proinflammatory genes and to assess tissue inflammation. A strong acute inflammatory response characterized by neutrophilic influx, increased cytokine secretion [KC (keratinocyte chemoattractant), TNF-α (tumour necrosis factor α), MIP-2 (macrophage inflammatory protein 2), MIP-1α and MCP-1 (monocyte chemoattractant protein-1)], pro-inflammatory gene expression [KC, MIP-2 and MMP12 (matrix metalloproteinase 12)] and up-regulated GM-CSF (granulocyte macrophage colony-stimulating factor) production was observed in the mainstream model. After sidestream exposure there was a dampened inflammatory reaction consisting only of macrophages and diminished GM-CSF levels, most likely caused by elevated CO concentrations. These results demonstrate that the composition of CS determines the dynamics of inflammatory cell recruitment in COPD mouse models. Different initial inflammatory processes might contribute to COPD pathogenesis in significantly varying ways, thereby determining the outcome of the studies.

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