Exposure to ambient particles accelerates monocyte release from bone marrow in atherosclerotic rabbits
Yukinobu Goto,1
James C. Hogg,1
Chih-Horng Shih,1
Hiroshi Ishii,1
Renaud Vincent,2 and
Stephan F. van Eeden1
1James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia V6Z 1Y6; and 2Environmental Health Directorate, Health Canada, Ottawa, Ontario, Canada K1A 0L2
Submitted 2 December 2003
; accepted in final form 27 February 2004
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ABSTRACT
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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 PM10 exposure. WHHL rabbits were given twice weekly intrapharyngeal instillations of 5 mg of PM10 for 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). PM10 instillation 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 PM10 exposure accelerates this process in relation to the amount of particles phagocytosed by alveolar macrophages.
air pollution; alveolar macrophages; atherosclerosis; inflammation; leukocytes
ATMOSPHERIC CONTAMINATION by ambient particulate matter [particles <10 µm (PM10)] causes excessive morbidity and mortality from cardiopulmonary events (5, 7, 22). It is estimated that an increase in PM10 of 10 µg/m3 increases total daily mortality by 1.8%, respiratory mortality by 3.4% and cardiovascular mortality by 1.4% (5, 7). Elevation of atmospheric PM10 concentration also increases the risk of chronic obstructive pulmonary disease (22) or acute myocardial infarction (21). Subjects with preexisting conditions, such as vascular diseases and diabetes mellitus, and the elderly are at particular risk for these air pollution-induced adverse health effects (21, 26, 39). Seaton and colleagues (27) proposed that the inhalation of these fine particles provokes a low-grade inflammatory response in the lung, followed by an exacerbation of preexisting lung disease and a change in blood coagulability that results in increased pulmonary and cardiovascular events. Subsequent studies have shown that repeated PM10 exposure stimulates the bone marrow to increase the production and release of circulating immature polymorphonuclear leukocytes (PMN) as a systemic inflammatory response (18, 30) and also that this response is associated with the destabilization of atherosclerotic plaques in the coronary arteries and aorta (30).
Monocytes play a key role in the pathogenesis of atherosclerotic lesions by adhering to the arterial endothelium, migrating into the subendothelial space, and differentiating into macrophages that scavenge lipids to become foam cells (10, 24). The inflammatory changes at the vascular intima include an interaction between PMN and endothelium that assists in monocyte accumulation through the production of monocyte chemotactic protein (MCP)-1 (25). Inflammatory mediators released by alveolar macrophages (AM) and lung epithelial cells following exposure to PM10 stimulate the bone marrow to release PMN (9, 19, 29, 32). We have previously shown that PM10 exposure induced a systemic inflammatory response that includes stimulation of the marrow with an expansion of the marrow pool of PMN and increase in circulating band cells (18). It also causes progression of atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits (30). The present study was designed to determine the natural rate of monocytopoiesis in these animals and measure the effect of PM10 exposure on this process. Rabbits were exposed to ambient particles for 4 wk using a protocol previously described (18, 30), and bone marrow monocyte response was measured using the thymidine analog 5'-bromo-2'-deoxyuridine (BrdU) to label the dividing monocyte precursor cells in the bone marrow (12).
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MATERIALS AND METHODS
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Urban air particulate.
The PM10 particles (EHC-93) were obtained from Environmental Health Directorate, Health Canada (Ottawa, ON, Canada). A detailed analysis of the EHC-93, including the elemental composition, has been described elsewhere (37). The particles were recovered from nylon bag filters with a nominal cutoff of 0.3 µm from a single-pass filtration system of the Environmental Health Centre in Ottawa (100% outdoor air). This dust sample has a mean particle diameter of 0.8 ± 0.4 µm (median ± SD) with 99% of particles <3.0 µm. The EHC-93 contains a small amount of endotoxin (6.4 ± 1.8 estimated units/ml or <3.0 ng/ml) that has been shown not to stimulate AM or bronchial epithelial cells in vitro or cause either a local or systemic effect when instilled into the lung of rabbits (3, 9, 17).
Experimental animals.
Female WHHL rabbits (38) (n = 10; weight, 2.9 ± 0.3 kg; Covance Research Products, Denver, PA) were used in this study. All animals were 42 wk old at the start of the experimental protocol and were fed standard rabbit chow. We also used female New Zealand White (NZW) rabbits (n = 6; weight, 2.5 ± 0.9 kg) without atherosclerosis as additional controls. The protocol was approved by the Animal Experimentation Committee of University of British Columbia.
Experimental design.
The animals were challenged with intrapharyngeal instillation (18) of either the particles suspended in saline (WHHL, n = 5) or just saline (WHHL, n = 5; NZW, n = 6). Briefly, the rabbits were anesthetized with 4% isoflurane, and 1 ml of normal saline or PM10 (5 mg of EHC-93 mixed with 1 ml of saline) was instilled twice a week for 4 wk, as previously described in detail (18, 30). The dividing cells in the bone marrow were labeled by infusing 100 mg/kg of BrdU (Sigma Chemical, St. Louis, MO) intravenously 24 h before the sixth instillation (30). Blood samples obtained from the central ear artery just before (baseline) and at intervals 7 days after the initial instillation of PM10 were used to measure total leukocyte counts and were also taken at intervals from 4 to 168 h or 24168 h after BrdU injection to determine the number of BrdU-labeled monocytes (MOBrdU) or PMN (PMNBrdU), respectively (12, 34). Differential white blood cell (WBC) counts were determined by counting 200 leukocytes in randomly selected fields of view on Wright-Giemsa-stained blood smears. Sedation [fentanyl (20 µg/kg) and droperidol (1 mg/kg)] was administered by subcutaneous injection to facilitate blood collection. The rabbits were killed 4 days after the last (8th) instillation with an overdose of pentobarbital sodium, and the lungs and aorta were removed for histological evaluation using methods previously described in detail (18, 30).
Immunohistochemical detection of BrdU-labeled leukocytes in the circulation.
Monocytes were identified using RbM2 (ICN Biomedicals, Aurora, OH), a monoclonal antibody specific for rabbit monocyte lysosomal antigen (28). To determine the fraction of MOBrdU in the circulation, cells on cytospin preparations (12) were stained for the presence of both monocyte cytoplasm RbM2 antigen (red) and nuclear BrdU (blue) (12) using the alkaline phosphatase and antialkaline phosphatase method (6).
Cytospin preparations were also stained by the APAAP method using anti-BrdU monoclonal antibody Bu20a (Dako Laboratories, Copenhagen, Denmark) to determine the fraction of PMNBrdU (4). MOBrdU and PMNBrdU or the different subpopulations of PMNBrdU (G3, G2, and G1 cells) were evaluated, and their transit through the bone marrow was calculated as previously described in detail (12, 34). All slides were coded and evaluated by investigators without knowledge of their origin.
Histology of the lungs.
Random histological sections of formalin-fixed, paraffin-embedded lung tissue stained with hematoxylin-eosin were examined for AM-containing particles. AM were divided into three categories: macrophages containing no particles in their cytoplasm (negative), <5% of the AM cytoplasm containing PM10, or >5% of the AM cytoplasm containing PM10 (18).
Statistical analysis.
The results are expressed as means ± SE and analyzed using a repeated-measure ANOVA over time where the effect of multiple comparisons was corrected using the Bonferroni method. The transit times of MOBrdU or PMNBrdU were compared by one-way ANOVA, followed by Fisher's protected least significant differences test as the post hoc test among the groups. The correlation between parameters was examined by Spearman's rank correlation test. A corrected P < 0.05 was considered significant throughout the study.
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RESULTS
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Distribution of PM10 in the lung.
AM-containing particles in the PM10 group of WHHL rabbits were distributed diffusely in all lung regions and had a higher percentage of particle-positive AM (17.1 ± 5.4% vs. 3.5 ± 0.7%, PM10 vs. control, P = 0.026; Fig. 1). Most positive AM have <5% of the AM cytoplasm occupied by particles (14.4 ± 4.3% vs. 3.3 ± 0.6%, PM10 vs. control, P = 0.021). There was no statistical difference in the percentage of particle-positive AM between WHHL and NZW controls.

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Fig. 1. Distribution of particulate matter, particles <10 µm (PM10), in the cytoplasmic surface area of alveolar macrophages exposed to PM10 (filled bars) for 4 wk or saline (control, open bars). A higher percentage of alveolar macrophages that phagocytosed particles was seen in PM10-exposed group, especially in which <5% of the cytoplasmic surface area was occupied by particles. Each value represents means ± SE from 5 Watanabe heritable hyperlipidemic (WHHL) rabbits. *P < 0.05 vs. control group. Please refer to the histology images in Refs. 18 and 30.
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Atherosclerosis in rabbits.
The volume fraction (Vv) of atherosclerotic lesions of the aorta was estimated as previously described (30). The values tended to be higher and more variable in the PM10 compared with the control group, but this was not statistically significant (29.5 ± 12.9% vs. 20.9 ± 3.5%, PM10 vs. control, P = not significant). However, there was a correlation between the percentage of AM positive for particles and the Vv of atherosclerotic lesions in the vessels (r2 = 0.694, P = 0.011). No atherosclerotic lesions were observed in the NZW rabbits.
Leukocytes in the circulation.
The repeated instillation exposure to PM10 did not change WBC, red blood cell, and platelet counts (data not shown) or monocyte and PMN counts compared with the control group (Fig. 2A). However, the percentage of circulating nonsegmented PMN (band cells) increased from the third week of exposure (Fig. 2B). The number of band cells in the circulation followed the same pattern (day 15: 17.4 ± 3.9 vs. 5.2 ± 2.7 x107/liter, PM10 vs. control, P < 0.05; day 20: 22.1 ± 2.2 vs. 4.9 ± 0.6 x107/liter, PM10 vs. control, P < 0.05). No significant difference was seen between the circulating leukocyte counts in WHHL and NZW controls.

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Fig. 2. Circulating polymorphonuclear leukocyte (PMN; squares) and monocyte (circles) counts (A) and the percentage of band cells (triangles; B) in the circulation of rabbits exposed to PM10 (filled symbols) for 4 wk or saline (control, open symbols). Arrows show the time points of PM10 instillation. The percentage of the circulating band cells increased from the third week of exposure (day 15). Values at each time point represent means ± SE from 5 WHHL rabbits. *P < 0.05 vs. control group.
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MOBrdU in the circulation.
Figure 3 shows the release of MOBrdU and PMNBrdU in the circulation from the marrow with or without PM10 instillation exposure in WHHL rabbits. The first MOBrdU appeared in the circulation 4 h after labeling, which was earlier than PMNBrdU (at 24 h). The fraction of MOBrdU reached a peak at 16 h (PM10 group) and 24 h (control), with a more rapid increase of MOBrdU in the circulation in the PM10 group (at 1216 h, P < 0.05). The curves for the percentage of MOBrdU in the circulation were similar to the curves for the numbers of MOBrdU. In contrast, there was no significant difference in the fraction and the number of PMNBrdU in the circulation between groups.

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Fig. 3. Release of 5'-bromo-2'-deoxyuridine (BrdU)-labeled monocytes (MOBrdU; circles) and BrdU-labeled PMN (PMNBrdU; squares) into the circulation after instillation exposure of WHHL rabbits to PM10 (filled symbols; n = 5) or saline (control, open symbols: n = 5) for 4 wk. The first MOBrdU and PMNBrdU appear in the circulation at 4 and 24 h after BrdU labeling, respectively. The data show that the percentage of MOBrdU increased more rapidly in the PM10-exposed group (a peak at 16 h) compared with the control group (a peak at 24 h). *P < 0.05 vs. controls. Each value represents means ± SE.
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To determine the size of the bone marrow pool, the cumulative number of MOBrdU or PMNBrdU in the circulation was calculated as previously described (33). Figure 4 shows the cumulative frequency distribution of MOBrdU, all PMNBrdU, and G1 cells (weakly stained PMNBrdU). The repeated PM10 instillation exposure did not change the overall size of the bone marrow pool of monocytes (Fig. 4A), but there was an increase in the size of the bone marrow mitotic pool of PMN (G1 cells, P < 0.05, Fig. 4C) in the PM10 group. Moreover, there was a correlation between the percentage of AM that have phagocytosed particles in the lung and the size of the bone marrow mitotic pool of PMN (r2 = 0.404, P = 0.029; Fig. 5B).

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Fig. 4. Cumulative number of MOBrdU (A), all PMNBrdU (B), and G1 cells (weakly stained PMN; C) in the circulation of rabbits exposed to PM10 (filled symbols) for 4 wk or saline (control, open symbols). Instillation exposure to PM10 increased the size of the marrow mitotic pool of PMN (G1 cells) but did not affect the size of bone marrow monocyte pool. *P < 0.05 vs. control group. Each value represents means ± SE from 5 WHHL rabbits.
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Fig. 5. Correlation between the percentage of alveolar macrophages that have phagocytosed PM10 and the transit time of monocytes through the bone marrow (A) and the bone marrow mitotic pool size of PMN (G1 cells; B) in WHHL rabbits.
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Transit time of monocytes through the marrow.
Table 1 shows the calculated mean transit time of MOBrdU, all PMNBrdU, and the different subpopulations of PMNBrdU (G3 and G1 cells) through the bone marrow. The monocyte transit times of the control WHHL rabbits was shorter than the control NZW rabbits (30.4 ± 1.9 h vs. 35.2 ± 0.9 h, P = 0.041). Moreover, the instillation exposure of the WHHL rabbits to PM10 further shortened monocyte marrow transit time (23.2 ± 1.6 h vs. 30.4 ± 1.9 h, P = 0.021). The transit time of MOBrdU through the marrow also correlated with the percentage of AM that had phagocytosed particles in the lung (r2 = 0.456, P = 0.019; Fig. 5A). The PM10 exposure did not change the transit time of all PMNBrdU through the marrow, but there was a trend toward a reduction of their transit time through the postmitotic pool of PMN (G3 cells, P = 0.054).
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DISCUSSION
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Recent work from our laboratory (30) has shown that repeated exposure to PM10 causes the progression of atherosclerosis in WHHL rabbits. These studies also showed an increase in circulating immature PMN counts with an increase in the size of the bone marrow mitotic pool of PMN. The present study extends these observations by showing that PM10 exposure accelerates the release of monocytes from the bone marrow as a part of the systemic response to the deposition of PM10 in the lung. This was associated with an increase in the bone marrow turnover of monocytes and a shortening of their transit time through the marrow without increasing the monocyte marrow pool size. The extent of this stimulation of the bone marrow by PM10 exposure was related to the extent of PM10 phagocytosed by AM in the lung. These monocytes released from the bone marrow appear into the circulation earlier than PMN. Together, these results show that PM10 exposure stimulates the bone marrow to accelerate the release of monocytes with a different pattern from PMN.
Controlled inhalation of ambient particles by animals induces both pulmonary and cardiovascular changes (2, 5, 37). Several reports, including our own (1, 13, 18), have used instillation of particles and documented similar cardiopulmonary change. Instillation of particles allows more accurate control of the amount of particles that reaches the airways and lung cells that process these particles. Experimental animals have different patterns of breathing and filtering ambient particles; instillation, therefore, provides a convenient experimental tool to quantify the local and the systemic inflammatory response elicited by exposure to particles. We used intrapharyngeal instillation in our study to promote diffuse deposition and avoid localized deposition of particles in the lung. This method is well described in our previous studies (18, 30). These studies showed that
20% (1 mg) of the dose delivered by intrapharyngeal instillation was aspirated into the lung, and <4% reached the alveolar surface. This dose of particles is comparable with other animal experiments and is relevant to human exposure (2, 18, 31). We calculated an alveolar exposure of 3.1 ng/cm2 for each dose or 24.8 ng/cm2 throughout the study period. Assuming a 6.5-m2 alveolar surface area for a 2.9-kg rabbit, the magnitude of exposure is smaller than an estimated human exposed to 35.1 ng/cm2 for 90 days at the average concentration in six U.S. cities (7).
The WHHL rabbits are hyperlipidemic as a result of consistent inbreeding from mutant rabbits (38). Their clinical features include spontaneous development of aortic atherosclerosis that bears a marked resemblance to human atherosclerosis (38). Because subjects with preexisting vascular disease and the elderly are at particular risk for these air pollution-induced adverse health effects (21, 26, 39), we have used these rabbits that naturally develop atherosclerosis. The present results confirmed that repeated exposure to PM10 increased the size of the bone marrow mitotic pool of PMN and released more immature PMN (band cells) from the marrow without a clearly measurable effect on PMN bone marrow transit times (Figs. 2B and 4C and Table 1). Because of lower circulating PMN counts in PM10-exposed rabbits in our current study (Fig. 2A), the calculated PMN mitotic pool size was larger in our previous study (30). In contrast, the same exposure was associated with an accelerated monocyte transit time through the marrow and an increase in their release into the circulation with no change in marrow pool size (Figs. 3 and 4A and Table 1). Together, these results confirm our previous reports on the behavior of PMN after particulate exposure (18, 30) and extend these observations by showing a different pattern of monocyte release following the same stimulation. Moreover, our results show a correlation between the percentage of AM that phagocytosed PM10 and the bone marrow transit time of monocytes (Fig. 5A), suggesting that the deposition of PM10 in the lung accelerates the release of monocytes from the marrow. The present data also show that the monocyte bone marrow pool size is independent of PM10 exposure (Fig. 4A), which supports the concept that newly formed monocytes enter the circulation immediately without undergoing a maturation process in the marrow (12, 15, 36).
Work from several laboratories, including our own (9, 16, 35), has shown that AM and lung epithelial cells both secrete cytokines when exposed to PM10 and that this production is enhanced by interaction between these cell types (9). We have also shown that several of these mediators are capable of stimulating the bone marrow as part of a systemic inflammatory response (19, 29, 32). The hematopoeitic growth factors, granulocyte/macrophage (GM)-CSF and monocyte colony-stimulating factor, IL-6, and the
-chemokines, all mediators produced by AM and lung epithelial cells, are thought to be important mediators for the production and mobilization of monocytes from the bone marrow (20). For example, the importance of IL-6 in monocytopoiesis was demonstrated in vitro in serum-deprived bone marrow cultures where the addition of exogenous IL-6 to cultures stimulated with GM-CSF resulted in increased numbers of monocytic colonies (14). We previously reported that human AM exposed to PM10 in vitro produce tumor necrosis factor (TNF)-
in a dose-dependent manner (17, 35). An early event in the pathogenesis of atherosclerosis is the adherence of monocytes to the arterial endothelium followed by migration into the lesion where they become lipid-taken foam cells (10, 24). TNF-
is known to upregulate the secretion of MCP-1 by endothelial cells (23) to promote the migration of monocytes into atherosclerotic lesions and activate arterial endothelium to increase L-selectin-dependent monocyte adhesion (11).
Monocyte accumulation in the inflammatory sites is induced by the local production of chemotactic factors (8). Schratzberger and colleagues (25) showed that interaction between PMN and the endothelium causes the release of active MCP-1, which assists in the recruitment of monocytes into atherosclerotic lesions. Interestingly, our data also show that the monocyte bone marrow transit times of the control WHHL rabbits with atherosclerosis are shorter than those of NZW rabbits without atherosclerosis (30.4 ± 1.9 h vs. 35.2 ± 0.9 h, P = 0.041, Table 1). This supports the concept that atherosclerosis is an inflammatory process that includes a systemic inflammatory response. Our data suggest that as part of this systemic inflammatory response, the bone marrow monocyte production is increased and that this production is further accelerated by the deposition of atmosphere particulates in the lung. These results support the hypothesis that PM10 exposure induces the release of monocytes into the circulation, and we speculate that they may contribute to the accelerated atherogenesis associated with exposure to particulate matter air pollution.
In summary, our results show that the monocyte transit times are shorter in WHHL rabbits with atherosclerosis, and chronic PM10 deposition in the lung further accelerates the release of monocytes from the bone marrow. These monocytes are released into the circulation earlier than PMN in response to PM10, and the number released is related to the amount of particles phagocytosed by AM in the lung. We postulate that these newly released monocytes may play a critical role in the accelerated atherogenesis associated with particulate air pollution.
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GRANTS
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This work was supported by grants from the British Columbia Lung Association, Canadian Institute for Health Research, the Toxic Substance Research Initiative, and Heart and Stroke Foundation of British Columbia and Yukon.
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ACKNOWLEDGMENTS
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S. van Eeden is the recipient of a Career Investigator Award from the American Lung Association and the William Thurlbeck Distinguished Researcher Award.
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FOOTNOTES
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Address for reprint requests and other correspondence: S. F. van Eeden, James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, St. Paul's Hospital, Univ. of British Columbia, 1081 Burrard St., Vancouver, BC, Canada V6Z 1Y6 (E-mail: svaneeden{at}mrl.ubc.ca).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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REFERENCES
|
---|
- Adamson IY, Vincent R, and Bakowska J. Differential production of metalloproteinases after instilling various urban air particle samples to rat lung. Exp Lung Res 29: 375388, 2003.[CrossRef][ISI][Medline]
- Adamson IY, Vincent R, and Bjarnason SG. Cell injury and interstitial inflammation in rat lung after inhalation of ozone and urban particulates. Am J Respir Cell Mol Biol 20: 10671072, 1999.[Abstract/Free Full Text]
- Becker S and Soukup JM. Exposure to urban air particulates alters the macrophage-mediated inflammatory response to respiratory viral infection. J Toxicol Environ Health 57: 445457, 1999.[CrossRef][ISI]
- Bicknell S, van Eeden S, Hayashi S, Hards J, English D, and Hogg JC. A non-radioisotopic method for tracing neutrophils in vivo using 5'-bromo-2'-deoxyuridine. Am J Respir Cell Mol Biol 10: 1623, 1994.[Abstract]
- Committee of the Environmental and Occupational Health Assembly of the American Thoracic Society. Health effects of outdoor air pollution. Am J Respir Crit Care Med 153: 350, 1996.[Abstract]
- Cordell JL, Falini B, Erber WN, Ghosh AK, Abdulaziz Z, MacDonald S, Pulford KA, Stein H, and Mason DY. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 32: 219229, 1984.[Abstract]
- Dockery DW, Pope CA III, Xu X, Spengler JD, Ware JH, Fay ME, Ferris BG Jr, and Speizer FE. An association between air pollution and mortality in six US cities. N Engl J Med 329: 17531759, 1993.[Abstract/Free Full Text]
- Doherty DE, Haslett C, Tonnesen MG, and Henson PM. Human monocyte adherence: a primary effect of chemotactic factors on the monocyte to stimulate adherence to human endothelium. J Immunol 138: 17621771, 1987.[Abstract/Free Full Text]
- Fujii T, Hayashi S, Hogg JC, Mukae H, Suwa T, Goto Y, Vincent R, and van Eeden SF. Interaction of alveolar macrophages and airway epithelial cells following exposure to particulate matter produces mediators that stimulate the bone marrow. Am J Respir Cell Mol Biol 27: 3441, 2002.[Abstract/Free Full Text]
- Gerrity RG. The role of the monocyte in atherogenesis: I. Transition of blood-borne monocytes into foam cells in fatty lesions. Am J Pathol 103: 181190, 1981.[Abstract]
- Giuffre L, Cordey AS, Monai N, Tardy Y, Schapira M, and Spertini O. Monocyte adhesion to activated aortic endothelium: role of L-selectin and heparan sulfate proteoglycans. J Cell Biol 136: 945956, 1997.[Abstract/Free Full Text]
- Goto Y, Hogg JC, Suwa T, Quinlan KB, and van Eeden SF. A novel method to quantify the turnover and release of monocytes from the bone marrow using the thymidine analog 5'-bromo-2'-deoxyuridine. Am J Physiol Cell Physiol 285: C253C259, 2003.[Abstract/Free Full Text]
- Henderson RF, Driscoll KE, Harkema JR, Lindenschmidt RC, Chang IY, Maples KR, and Barr EB. A comparison of the inflammatory response of the lung to inhaled versus instilled particles in F344 rats. Fundam Appl Toxicol 24: 183197, 1995.[CrossRef][ISI][Medline]
- Jansen JH, Kluin-Nelemans JC, Van Damme J, Wientjens GJ, Willemze R, and Fibbe WE. Interleukin 6 is a permissive factor for monocytic colony formation by human hematopoietic progenitor cells. J Exp Med 175: 11511154, 1992.[Abstract]
- Meuret G and Hoffmann G. Monocyte kinetic studies in normal and disease states. Br J Haematol 24: 275285, 1973.[ISI][Medline]
- Mills PR, Davies RJ, and Devalia JL. Airway epithelial cells, cytokines, and pollutants. Am J Respir Crit Care Med 160: S38S43, 1999.[Abstract/Free Full Text]
- Mukae H, Hogg JC, English D, Vincent R, and van Eeden SF. Phagocytosis of particulate air pollutants by human alveolar macrophages stimulates the bone marrow. Am J Physiol Lung Cell Mol Physiol 279: L924L931, 2000.[Abstract/Free Full Text]
- Mukae H, Vincent R, Quinlan K, English D, Hards J, Hogg JC, and van Eeden SF. The effect of repeated exposure to particulate air pollution (PM10) on the bone marrow. Am J Respir Crit Care Med 163: 201209, 2001.[Abstract/Free Full Text]
- Nakagawa M, Terashima T, D'Yachkova Y, Bondy GP, Hogg JC, and van Eeden SF. Glucocorticoid-induced granulocytosis: contribution of marrow release and demargination of intravascular granulocytes. Circulation 98: 23072313, 1998.[Abstract/Free Full Text]
- Oppenheim J. Human chemokines: an update. Annu Rev Immunol 15: 675705, 1998.[CrossRef][ISI][Medline]
- Peters A, Dockery DW, Muller JE, and Mittleman MA. Increased particulate air pollution and the triggering of myocardial infarction. Circulation 103: 28102815, 2001.[Abstract/Free Full Text]
- Pope CA III, Thun MJ, Namboodiri MM, Dockery DW, Evans JS, Speizer FE, and Heath CW Jr. Particulate air pollution as a predictor of mortality in a prospective study of U.S. adults. Am J Respir Crit Care Med 151: 669674, 1995.[Abstract]
- Rollins BJ, Yoshimura T, Leonard EJ, and Pober JS. Cytokine-activated human endothelial cells synthesize and secrete a monocyte chemoattractant, MCP-1/JE. Am J Pathol 136: 12291233, 1990.[Abstract]
- Ross R. The pathogenesis of atherosclerosisan update. N Engl J Med 314: 488500, 1986.[ISI][Medline]
- Schratzberger P, Dunzendorfer S, Reinisch N, Kahler CM, Herold M, and Wiedermann CJ. Release of chemoattractants for human monocytes from endothelial cells by interaction with neutrophils. Cardiovasc Res 38: 516521, 1998.[CrossRef][ISI][Medline]
- Schwartz J. Short term fluctuations in air pollution and hospital admissions of the elderly for respiratory disease. Thorax 50: 531538, 1995.[Abstract]
- Seaton A, MacNee W, Donaldson K, and Godden D. Particulate air pollution and acute health effects. Lancet 345: 176178, 1995.[CrossRef][ISI][Medline]
- Shimokawa Y, Takeya M, Miyauchi Y, and Takahashi K. A monoclonal antibody, RbM2, specific for a lysosomal membrane antigen of rabbit monocyte/macrophages. Immunology 70: 513519, 1990.[ISI][Medline]
- Suwa T, Hogg JC, English D, and Van Eeden SF. Interleukin-6 induces demargination of intravascular neutrophils and shortens their transit in marrow. Am J Physiol Heart Circ Physiol 279: H2954H2960, 2000.[Abstract/Free Full Text]
- Suwa T, Hogg JC, Quinlan KB, Ohgami A, Vincent R, and van Eeden SF. Particulate air pollution induces progression of atherosclerosis. J Am Coll Cardiol 39: 935942, 2002.[CrossRef][ISI][Medline]
- Tan WC, Qiu D, Liam BL, Ng TP, Lee SH, van Eeden SF, D'Yachkova Y, and Hogg JC. The human bone marrow response to acute air pollution caused by forest fires. Am J Respir Crit Care Med 161: 12131217, 2000.[Abstract/Free Full Text]
- Terashima T, English D, Hogg JC, and van Eeden SF. Release of polymorphonuclear leukocytes from the bone marrow by interleukin-8. Blood 92: 10621069, 1998.[Abstract/Free Full Text]
- Terashima T, Wiggs B, English D, Hogg JC, and van Eeden SF. The effect of cigarette smoking on the bone marrow. Am J Respir Crit Care Med 155: 10211026, 1997.[Abstract]
- Terashima T, Wiggs B, English D, Hogg JC, and van Eeden SF. Polymorphonuclear leukocyte transit times in bone marrow during streptococcal pneumonia. Am J Physiol Lung Cell Mol Physiol 271: L587L592, 1996.[Abstract/Free Full Text]
- Van Eeden SF, Tan WC, Suwa T, Mukae H, Terashima T, Fujii T, Qui D, Vincent R, and Hogg JC. Cytokines involved in the systemic inflammatory response induced by exposure to particulate matter air pollutants (PM10). Am J Respir Crit Care Med 164: 826830, 2001.[Abstract/Free Full Text]
- Van Furth R, Diesselhoff-den Dulk MC, and Mattie H. Quantitative study on the production and kinetics of mononuclear phagocytes during an acute inflammatory reaction. J Exp Med 138: 13141330, 1973.[ISI][Medline]
- Vincent R, Bjarnason SG, Adamson IY, Hedgecock C, Kumarathasan P, Guenette J, Potvin M, Goegan P, and Bouthillier L. Acute pulmonary toxicity of urban particulate matter and ozone. Am J Pathol 151: 15631570, 1997.[Abstract]
- Watanabe Y. Serial inbreeding of rabbits with hereditary hyperlipidemia (WHHL-rabbit). Atherosclerosis 36: 261268, 1980.[ISI][Medline]
- Zanobetti A and Schwartz J. Cardiovascular damage by airborne particles: are diabetics more susceptible? Epidemiology 13: 588592, 2002.[CrossRef][ISI][Medline]
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