Exposure to ambient particles accelerates monocyte release from bone marrow in atherosclerotic rabbits

2004 ◽  
Vol 287 (1) ◽  
pp. L79-L85 ◽  
Author(s):  
Yukinobu Goto ◽  
James C. Hogg ◽  
Chih-Horng Shih ◽  
Hiroshi Ishii ◽  
Renaud Vincent ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Transit Time ◽  
Alveolar Macrophages ◽  
Ambient Particles ◽  
Cell Counts ◽  
Thymidine Analog ◽  
Rapid Release ◽  
Dividing Cells ◽  
Progression Of Atherosclerosis ◽  
Stimulation Of

Exposure to air pollution [particulate matter, particles <10 μm (PM10)] causes a systemic inflammatory response that includes stimulation of the bone marrow (BM) and progression of atherosclerosis. Monocytes are known to play a key role in atherogenesis by migration into subendothelial lesions where they appear as foam cells. The present study was designed to quantify the BM monocyte response in Watanabe heritable hyperlipidemic (WHHL) rabbits after PM10exposure. WHHL rabbits were given twice weekly intrapharyngeal instillations of 5 mg of PM10for 4 wk to a total of 40 mg and compared with control WHHL or New Zealand White (NZW) rabbits. The thymidine analog 5′-bromo-2′-deoxyuridine was used to label dividing cells in the BM and a monoclonal antibody to identify monocytes in peripheral blood. The transit time of monocytes through the BM was faster in WHHL than in NZW rabbits (30.4 ± 1.9 h vs. 35.2 ± 0.9 h, WHHL vs. NZW; P < 0.05). PM10instillation exposure increased circulating band cell counts, caused rapid release of monocytes from the BM, and further shortened their transit time through the BM to 23.2 ± 1.6 h ( P < 0.05). The percentage of alveolar macrophages containing particles in the lung correlated with the BM transit time of monocytes (r2= 0.45, P <0.05). We conclude that atherosclerosis increases the release of monocytes from the BM, and PM10exposure accelerates this process in relation to the amount of particles phagocytosed by alveolar macrophages.

scholarly journals Novel properties of statins: suppression of the systemic and bone marrow responses induced by exposure to ambient particulate matter (PM10) air pollution

2012 ◽  
Vol 303 (6) ◽  
pp. L492-L499 ◽  
Author(s):  
Ryohei Miyata ◽  
Ni Bai ◽  
Renaud Vincent ◽  
Don D. Sin ◽  
Stephan F. Van Eeden
Keyword(s):  
Bone Marrow ◽  
Particulate Matter ◽  
Transit Time ◽  
Polymorphonuclear Leukocytes ◽  
Inflammatory Responses ◽  
Ambient Particulate Matter ◽  
Bone Marrow Stimulation ◽  
Dividing Cells ◽  
Prolonged Retention ◽  
Progression Of Atherosclerosis

Exposure to ambient particulate matter (PM10) elicits systemic inflammatory responses that include the stimulation of bone marrow and progression of atherosclerosis. The present study was designed to assess the effect of repeated exposure of PM10on the turnover and release of polymorphonuclear leukocytes (PMNs) from the bone marrow into the circulation and the effect of lovastatin on the PM10-induced bone marrow stimulation. Rabbits exposed to PM10three times a week for 3 wk, were given a bolus of 5′-bromo-2′-deoxyuridine to label dividing cells in the marrow to calculate the transit time of PMNs in the mitotic or postmitotic pool. PM10exposure accelerated the turnover of PMNs by shortening their transit time through the marrow (64.8 ± 1.9 h vs. 34.3 ± 7.4 h, P < 0.001, control vs. PM10). This was predominantly due to a rapid transit of PMNs through the postmitotic pool (47.9 ± 0.7 h vs. 21.3 ± 4.3 h, P < 0.001, control vs. PM10) but not through the mitotic pool. Lovastatin delayed the transit time of postmitotic PMNs (38.2 ± 0.5 h, P < 0.001 vs. PM10) and shifted the postmitotic PMN release peak from 30 h to 48 h. PM10exposure induced the prolonged retention of newly released PMNs in the lung, which was reduced by lovastatin ( P < 0.01). PM10exposure increased plasma interleukin-6 levels with significant reduction by lovastatin ( P < 0.01). We conclude that lovastatin downregulates the PM10-induced overactive bone marrow by attenuating PM10-induced systemic inflammatory responses.

Phagocytosis of particulate air pollutants by human alveolar macrophages stimulates the bone marrow

2000 ◽  
Vol 279 (5) ◽  
pp. L924-L931 ◽  
Author(s):  
Hiroshi Mukae ◽  
James C. Hogg ◽  
Dean English ◽  
Renaud Vincent ◽  
Stephan F. Van Eeden
Keyword(s):  
Bone Marrow ◽  
Transit Time ◽  
Alveolar Macrophages ◽  
Epidemiologic Studies ◽  
Dependent Manner ◽  
Ambient Particulate Matter ◽  
Cell Counts ◽  
Human Alveolar Macrophages ◽  
Factor Α ◽  
Dose Dependent

Epidemiologic studies have shown an association between the level of ambient particulate matter < 10 μm (PM10) and cardiopulmonary mortality. We have shown that exposure of rabbits to PM10stimulates the bone marrow. In this study, we determined whether human alveolar macrophages (AMs) that phagocytose atmospheric PM10produce mediators capable of stimulating the bone marrow. AMs incubated with PM10for 24 h produced tumor necrosis factor-α in a dose-dependent manner (86.8 ± 53.29 pg/ml with medium alone; 1,087.2 ± 257.3 pg/ml with 0.1 mg/ml of PM10; P < 0.02). Instillation of the supernatants from AMs incubated with 0.1 mg/ml of PM10into the lungs of rabbits ( n = 6) increased circulating polymorphonuclear leukocyte (PMN) and band cell counts as well as shortened the PMN transit time through the bone marrow (87.9 ± 3.3 h) compared with unstimulated human AMs (104.9 ± 2.4 h; P < 0.01; n = 5 rabbits). The supernatants from rabbit AMs incubated with 0.1 mg/ml of PM10( n = 4 rabbits) caused a similar shortening in the PMN transit time through the bone marrow (91.5 ± 1.6 h) compared with human AMs. We conclude that mediators released from AMs after phagocytosis of PM10induce a systemic inflammatory response that includes stimulation of the bone marrow.

A novel method to quantify the turnover and release of monocytes from the bone marrow using the thymidine analog 5′-bromo-2′-deoxyuridine

2003 ◽  
Vol 285 (2) ◽  
pp. C253-C259 ◽  
Author(s):  
Yukinobu Goto ◽  
James C. Hogg ◽  
Tatsushi Suwa ◽  
Kevin B. Quinlan ◽  
Stephan F. van Eeden
Keyword(s):  
Bone Marrow ◽  
Streptococcus Pneumoniae ◽  
Transit Time ◽  
Half Life ◽  
Double Immunostaining ◽  
Thymidine Analog ◽  
Novel Method

The present study was designed to develop methods to study the production and release of monocytes from the bone marrow using the thymidine analog 5′-bromo-2′-deoxyuridine (BrdU). Dividing monocytes in bone marrow were labeled with BrdU (MOBrdU), and their release into the blood and disappearance from the circulation were monitored using a double immunostaining method. The first MOBrdUappeared in the circulation 4 h after labeling with BrdU and peaked at 18 h when 34.3 ± 5.8% of monocytes were labeled. The calculated transit time of monocytes through bone marrow was 38.1 ± 3.1 h in control rabbits with a half-life ( T1/2) of 12.7 h. Instillation of Streptococcus pneumoniae into the lung accelerated the release of monocytes from bone marrow (peak at 10 h) and shortened their bone marrow transit time (27.1 ± 1.8 vs. 22.6 ± 0.6, vehicle vs. pneumonia; P < 0.05). We conclude that this nonradioisotope method provides a novel way to monitor monocyte kinetics and confirmed previous reports that a focal pneumonia shortens monocyte marrow transit and increases their release into the circulation.

Thrombopoietin-Induced Stimulation of Megakaryocyte- Enriched Bone Marrow Cultures

1979 ◽  
Author(s):  
K. L. Kellar ◽  
B. L. Evatt ◽  
C. R. McGrath ◽  
R. B. Ramsey
Keyword(s):  
Bone Marrow ◽  
Dna Synthesis ◽  
Bone Marrow Cells ◽  
Rabbit Plasma ◽  
Bone Marrow Cultures ◽  
Plasma Fractions ◽  
Marrow Cultures ◽  
Stimulation Of

Liquid cultures of bone marrow cells enriched for megakaryocytes were assayed for incorporation of 3H-thymidine (3H-TdR) into acid-precipitable cell digests to determine the effect of thrombopoietin on DNA synthesis. As previously described, thrombopoietin was prepared by ammonium sulfate fractionation of pooled plasma obtained from thrombocytopenic rabbits. A control fraction was prepared from normal rabbit plasma. The thrombopoietic activity of these fractions was determined in vivo with normal rabbits as assay animals and the rate of incorporation of 75Se-selenomethionine into newly formed platelets as an index of thrombopoietic activity of the infused material. Guinea pig megakaryocytes were purified using bovine serum albumin gradients. Bone marrow cultures containing 1.5-3.0x104 cells and 31%-71% megakaryocytes were incubated 18 h in modified Dulbecco’s MEM containing 10% of the concentrated plasma fractions from either thrombocytopenic or normal rabbits. In other control cultures, 0.9% NaCl was substituted for the plasma fractions. 3H-TdR incorporation was measured after cells were incubated for 3 h with 1 μCi/ml. The protein fraction containing thrombopoietin-stimulating activity caused a 25%-31% increase in 3H-TdR incorporation over that in cultures which were incubated with the similar fraction from normal plasma and a 29% increase over the activity in control cultures to which 0.9% NaCl had been added. These data suggest that thrombopoietin stimulates DNA synthesis in megakaryocytes and that this tecnique may be useful in assaying thrombopoietin in vitro.

NUMERICAL SIMULATION OF THE ROLE OF CO-TRANSMISSION BY ACETYLCHOLINE AND SEROTONIN ON MOTILITY OF THE GUT

2006 ◽  
Vol 06 (04) ◽  
pp. 399-428
Author(s):  
R. MIFTAHOF
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Transit Time ◽  
Receptor Agonist ◽  
Muscle Cells ◽  
Receptor Antagonists ◽  
One Dimensional ◽  
Circular Smooth Muscle ◽  
Spatio Temporal ◽  
Stimulation Of

Electrophysiological mechanisms of co-transmission by serotonin (5-HT) and acetylcholine (ACh), co-expression of their receptor types, i.e., 5-HT type 3 and 4, nicotinic cholinerginc (nACh) and muscarinic cholinergic (μACh), and effects of selective and non-selective 5-HT3 and 5-HT4 receptor agonists/antagonists, on electromechanical activity of the gut were studied numerically. Two series of numerical experiments were performed. First, the dynamics of the generation and propagation of electrical signals interconnected with the primary sensory (AH) neurons, motor (S) neurons and smooth muscle cells were studied in a one-dimensional model. Simulations showed that stimulation of the 5-HT3 receptors reduced the threshold of activation of the mechanoreceptors by 17.6%. Conjoint excitation of the 5-HT3 and 5-HT4 receptors by endogenous serotonin converted the regular firing pattern of electrical discharges of the AH and S neurons to a beating mode. Activation confined to 5-HT3 receptors, located on the somas of the adjacent AH and S type neurons, could not sustain normal signal transduction between them. It required ACh as a co-transmitter and co-activation of the nACh receptors. Application of selective 5-HT3 receptor antagonists inhibited dose-dependently the production of action potentials at the level of mechanoreceptors and the soma of the primary sensory neuron and increased the threshold activation of the mechanoreceptors. Normal mechanical contractile activity depended on co-stimulation of the 5-HT4 and μACh receptors on the membrane of smooth muscle cells. In the second series of simulations, which involved a spatio-temporal model of the functional unit, effects of co-transmission by ACh and 5-HT on the electromechanical response in a segment of the gut were analyzed. Results indicated that propagation of the wave of excitation between the AH and S neurons within the myenteric nervous plexus in the presence of 5-HT3 receptor antagonists was supported by co-release of ACh. Co-stimulation of 5-HT3, nACh and μACh receptors impaired propulsive activity of the gut. The bolus showed uncoordinated movements. In an ACh-free environment Lotronex (GlaxoSmithKline), a 5-HT3 receptor antagonist, significantly increased the transit time of the pellet along the gut. In the presence of ACh, Lotronex produced intensive tonic-type contractions in the longitudinal and circular smooth muscle layers and eliminated propulsive activity. The 5HT4 receptor agonist, Zelnorm (Novartis), preserved the reciprocal electromechanical relationships between the longitudinal and circular smooth muscle layers. The drug changed the normal propulsive pattern of activity to an expulsive (non-mixing) type. Treatment of the gut with selective 5HT4 receptor antagonists increased the transit time by disrupting the migrating myoelectrical complex. Cisapride (Janssen), a mixed 5HT3 and 5HT4 receptor agonist, increased excitability of the AH and S neurons and the frequency of slow waves. Longitudinal and circular smooth muscle syncytia responded with the generation of long-lasting tonic contractions, resulting in a "squeezing" type of pellet movement. Comparison of the theoretical results obtained on one-dimensional and spatio-temporal models to in vivo and in vitro experimental data indicated satisfactory qualitative, and where available, quantitative agreement.

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