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Abderrahim Nemmar

Publications and source records attributed to Abderrahim Nemmar.

15 recordsLinked to original sources
PubMed2006

Cardiovascular and lung inflammatory effects induced by systemically administered diesel exhaust particles in rats.

Pollution by particulates has consistently been associated with increased cardiorespiratory morbidity and mortality. It has been suggested that ultrafine particles, of which diesel exhaust particles (DEP) are significant contributors, are able to translocate from the airways into the bloodstream in vivo. In the present study, we assessed the effect of systemic administration of DEP on cardiovascular and respiratory parameters. DEP were administered into the tail vein of rats, and heart rate, blood pressure, blood platelet activation, and lung inflammation were studied 24 h later. Doses of 0.02, 0.1, or 0.5 mg DEP/kg (8, 42, or 212 microg DEP/rat) induced a significant decrease of heart rate and blood pressure compared with saline-treated rats. Although the number of platelets was not affected, all the doses of DEP caused a shortening of the bleeding time. Similarly, in addition to triggering lung edema, the bronchoalveolar lavage analysis revealed the presence of neutrophil influx in DEP-treated rats in a dose-dependent manner. We conclude that the presence of DEP in the systemic circulation leads not only to cardiovascular and haemostatic changes but it also triggers pulmonary inflammation.

Animals↗
PubMed2006

Quantification of extrapulmonary translocation of intratracheal-instilled particles in vivo in rats: effect of lipopolysaccharide.

Particulate air pollution is associated with respiratory and cardiovascular morbidity and mortality. However, important uncertainties remain in the quantification of extrapulmonary translocation of ultrafine particles into blood circulation. Therefore, the widely used radioiodinated technique was applied to radiolabel polystyrene particles with an average diameter of 56.4 and 202 nm, respectively. The extrapulmonary distribution of these particles (3.7 x 10(5) Bq/rat) was quantified at 0.5, 2, 24 and 120 h after intratracheal instillation in rats. Moreover, we have taken into account the possible involvement of pulmonary inflammation in this process. Rats which received a single intratracheal instillation of free 125I or a single intravenous injection of labeled ultrafine particles served as control. The results indicated that the pulmonary deposition of radioactivity was almost unchanged for both sizes. Only small amounts of radioactivity (1.64-2.49%) were recovered in blood shortly after administration of both types of particle, in healthy rats. However, the extent of particle translocation into the blood of the ultrafine size following the pretreatment with lipopolysaccharides was significantly higher (from 1.96 +/- 0.67 to 4.73 +/- 0.31%) compared to larger particles (from 2.19 +/- 0.77 to 2.21 +/- 0.64%). In conclusion, our findings suggest that only a small fraction of intratracheal-instilled ultrafine particles can pass rapidly into systemic circulation, but this translocation is markedly increased following LPS pretreatment. Thus, pulmonary inflammation seems to play a major role in enhancing the extrapulmonary translocation of particles.

Administration, Inhalation↗
PubMed2006

Effects of particulate air pollution on hemostasis.

Exposure to particulate air pollution is associated with acute and chronic cardiovascular morbidity and mortality. The mechanisms involved in these effects are not fully elucidated. Research has proved that fine particles, principally the ultrafine fraction, which are predominantly derived from combustion of fossil fuel, are the most toxic. Recent clinical and experimental studies have reported mechanistic observations linking fine and ultrafine particles to the coagulation cascade, platelet function, and subsequent development of atherosclerosis and thrombosis. These effects have been explained either by release of soluble mediators by the lungs, which affect blood coagulation parameters, or by the direct translocation of ultrafine particles into the systemic circulation or the alteration of autonomic cardiac control. Despite recent advances, additional studies are needed to investigate the pathophysiologic mechanisms linking particulate air pollution and hemostasis.

Air Pollutants↗
PubMed2005

Evaluation of particle translocation across the alveolo-capillary barrier in isolated perfused rabbit lung model.

Particulate air pollution is associated with respiratory and cardiovascular morbidity and mortality. It has been suggested that ultrafine particles are able to translocate from the airways into the bloodstream in vivo. We have investigated this in an isolated perfused and ventilated rabbit lung preparation lacking pulmonary lymphatic flow. Fluorescent polystyrene particles of different diameters (24, 110 or 190 nm) and surface chemistry (carboxylate or amine modified) were injected either intratracheally (i.t.) or intravascularly (i.v.) and, after a period of 2 h, their presence in the perfusion liquid or in the bronchoalveolar lavage (BAL) fluid, was assessed by spectrofluorimetry. Vascular pressures and lung weights were monitored. Following the i.t. administration, no particle translocation was observed from the alveoli into the vascular compartment. Similarly, no particle translocation was found after i.v. administration of particles. However, when microvascular permeability was pharmacologically increased by administering histamine (10(-4) M) in the vascular compartment, inducing a positive driving force provided by fluid filtration, a fluorescent signal in BAL was recorded (2.5 +/- 1% of the dose of particles administered), suggesting a translocation of particles through the alveolo-capillary barrier. We conclude that ultrafine polystyrene particles cannot significantly diffuse from lung into the vascular compartment in our model, but they are able to translocate in the opposite direction when the microvascular permeability is increased by histamine. The relevance of these ex vivo findings for the in vivo translocation of inhaled ultrafine particles remains to be established.

Air Pollutants↗
PubMed2005

Silica particles enhance peripheral thrombosis: key role of lung macrophage-neutrophil cross-talk.

RATIONALE: Inflammation and thrombosis are related via interactions between leukocytes, platelets, the vasculature, and the coagulation system. However, the mechanisms behind these interactions remain poorly understood. OBJECTIVES: We have investigated the effects of the well known pulmonary inflammation induced by silica for the development of peripheral thrombogenicity in a hamster model of thrombosis. In addition, the consequences of pulmonary macrophage and circulating monocyte and neutrophil depletion on the thrombogenicity were investigated. METHODS: Silica particles (2-200 mug/hamster) were intratracheally instilled, and experimental thrombosis in photochemically induced femoral vein lesions was assessed 24 hours later, in association with cellular infiltration in the lung. MEASUREMENTS AND MAIN RESULTS: Intratracheally instilled silica particles (20 and 200 mug/hamster) triggered pulmonary inflammation, together with stimulation of peripheral platelet-rich thrombus formation. Both the selective depletion of lung macrophages by intratracheal administration of clodronate liposomes and the combined depletion of circulating monocytes and neutrophils by intraperitoneal injection of cyclophosphamide significantly reduced silica-induced influx of macrophages and neutrophils in bronchoalveolar lavage, and reduced peripheral thrombogenicity. Silica-induced lung inflammation was accompanied by increased neutrophil elastase levels in bronchoalveolar lavage and in plasma. Specific neutrophil elastase inhibition in the lung did not affect lung inflammation but reduced peripheral thrombogenicity. CONCLUSION: These findings uncover pulmonary macrophage-neutrophil cross-talk releasing neutrophil elastase into the blood circulation. Elastase, triggering activation of circulating platelets, may then predispose platelets to initiate thrombotic events on mildly damaged vasculature.

Animals↗
PubMed2004

Pharmacological stabilization of mast cells abrogates late thrombotic events induced by diesel exhaust particles in hamsters.

BACKGROUND: Particulate air pollution is associated with cardiovascular diseases and myocardial infarction (MI). METHODS AND RESULTS: We investigated the relationship between airway inflammation and thrombosis 24 hours after intratracheal (IT) instillation of diesel exhaust particles (DEP; 50 microg/hamster). Mild thrombosis was induced in the femoral vein by endothelial injury, and the consequences of airway inflammation on thrombogenicity were studied via online video microscopy. Lung inflammation and histamine analysis in bronchoalveolar lavage (BAL) and plasma were performed after pretreatment with dexamethasone (DEX) or sodium cromoglycate (SC). DEP induced airway inflammation and histamine release in BAL and in plasma, and increased thrombosis, without elevating plasma von Willebrand factor (vWF) levels. The IT instillation of 400-nm positively charged polystyrene particles (500 microg/hamster), serving as particles that do not penetrate into the circulation, equally produced airway inflammation, histamine release, and enhanced thrombosis. Histamine in plasma resulted from basophil activation. Intraperitoneal (IP) pretreatment with DEX (5 mg/kg) abolished the DEP-induced histamine increase in BAL and plasma and abrogated airway inflammation and thrombogenicity. The IT pretreatment with DEX (0.5 mg/kg) showed a partial but parallel inhibition of all of these parameters. Pretreatment with SC (40 mg/kg, IP) strongly inhibited airway inflammation, thrombogenicity, and histamine release. CONCLUSIONS: Our results are compatible with the triggering of mast cell degranulation and histamine release by DEP. Histamine plays an initial central role in airway inflammation, further release of histamine by circulating basophils, and peripheral thrombotic events. Antiinflammatory pretreatment can abrogate the peripheral thrombogenicity by preventing histamine release from mast cells.

Air Pollutants↗
PubMed2004

Possible mechanisms of the cardiovascular effects of inhaled particles: systemic translocation and prothrombotic effects.

Particulate air pollution is associated with cardiovascular morbidity and mortality. Fine particles with a diameter <2.5 microm (PM2.5) have an important role in triggering biological responses. These particles, and particularly the ultrafine fraction (<100 nm) penetrate deeply into the respiratory tract. Recently, we have demonstrated that ultrafine particles are able to translocate from the lung into the systemic circulation in hamsters and humans. In urban areas, diesel engines are considered to be the major source of PM2.5. We therefore evaluated the acute effect (1 h) of diesel exhaust particles (DEP) in a hamster model of peripheral vascular thrombosis induced by free-radical mediated endothelial injury, using intravenous Rose Bengal and local illumination. Intratracheal doses of 5-500 microg of DEP per animal induced inflammation with elevation of neutrophils, total proteins and histamine in bronchoalveolar lavage. DEP enhanced experimental arterial and venous platelet rich-thrombus formation in vivo. Blood samples taken from hamsters 30 and 60 min after instillation of DEP caused platelet activation, when analyzed in the Platelet Function Analyser (PFA-100). The direct addition of DEP to untreated hamster blood also caused platelet aggregation. These effects persisted up to 24 h after instillation. Our results provide plausible mechanistic explanations for the epidemiologically established link between air pollution and acute cardiovascular effects.

Adult↗
PubMed2003

Pulmonary inflammation and thrombogenicity caused by diesel particles in hamsters: role of histamine.

Short-term increases in particulate air pollution are associated with increased incidence of cardiovascular events. Previously, we showed that intratracheally instilled diesel exhaust particles (DEPs) are prothrombotic. Here, we investigated the time course and the mechanisms. At 1, 6, and 24 hours after instillation of 50 microg DEPs per hamster, the mean size of in vivo-induced and quantified venous thrombosis was increased by 480%, 770%, and 460%, respectively. Platelets activation in blood was confirmed by a shortened closure time in the platelet function analyzer (PFA-100). In bronchoalveolar lavage, neutrophils and histamine levels were increased at all time points. In plasma, histamine was increased at 6 and 24 hours but not at 1 and 3 hours. Pretreatment with a histamine H1-receptor antagonist (diphenhydramine, 30 mg/kg intraperitoneally) abolished the DEP-induced neutrophil influx in bronchoalveolar lavage at all time points. However, diphenhydramine pretreatment did not affect DEP-induced thrombosis or platelet activation at 1 hour, whereas both were markedly reduced at 6 and 24 hours. In conclusion, pulmonary inflammation and peripheral thrombosis are correlated at 6 and 24 hours, but at 1 hour, the prothrombotic effects do not appear to result from pulmonary inflammation but possibly from the blood penetration of DEP-associated components or by DEP particles themselves.

Animals↗
PubMed2003

Diesel exhaust particles in lung acutely enhance experimental peripheral thrombosis.

BACKGROUND: Pollution by particulates has consistently been associated with increased cardiovascular morbidity and mortality, but a plausible biological basis for this association is lacking. METHODS AND RESULTS: Diesel exhaust particles (DEPs) were instilled into the trachea of hamsters, and blood platelet activation, experimental thrombosis, and lung inflammation were studied. Doses of 5 to 500 micro g of DEPs per animal induced neutrophil influx into the bronchoalveolar lavage fluid with elevation of protein and histamine but without lactate dehydrogenase release. The same doses enhanced experimental arterial and venous platelet rich-thrombus formation in vivo. Blood samples taken from hamsters 30 and 60 minutes after instillation of 50 micro g of DEPs yielded accelerated aperture closure (ie, platelet activation) ex vivo, when analyzed in the Platelet Function Analyser (PFA-100). The direct addition of as little as 0.5 micro g/mL DEPs to untreated hamster blood significantly shortened closure time in vitro. CONCLUSIONS: The intratracheal instillation of DEPs leads to lung inflammation as well as a rapid activation of circulating blood platelets. The kinetics of platelet activation are consistent with the reported clinical occurrence of thrombotic complications after exposure to pollutants. Our findings, therefore, provide a plausible explanation for the increase in cardiovascular morbidity and mortality accompanying urban air pollution.

Animals↗
PubMed2003

Size effect of intratracheally instilled particles on pulmonary inflammation and vascular thrombosis.

Particulate air pollution is associated with cardiorespiratory effects and ultrafine particles (UFPs, diameter < 100 nm) are believed to play an important role. We studied the acute (1 h) effect of intratracheally instilled unmodified (60 nm), negatively charged carboxylate-modified (60 nm), or positively charged amine-modified (60 or 400 nm) polystyrene particles on bronchoalveolar lavage (BAL) indices and on peripheral thrombosis in hamster. The latter was assessed by measuring the extent of photochemically induced thrombosis in a femoral vein via transillumination. Unmodified and negative UFPs did not modify thrombosis and BAL indices. Positive UFPs increased thrombosis at 500 microg per animal (+ 341 +/- 96%) and at 50 microg per animal (+ 533 +/- 122%), but not at 5 microg per animal. Neutrophils, lactate dehydrogenase, and histamine were increased in BAL at all these doses but protein concentration was increased only at 500 microg per animal. Positive 400-nm particles (500 microg per animal) did not affect thrombosis, although they led to a neutrophil influx and an increase in BAL proteins and histamine. Using the Platelet Function Analyser (PFA-100), the platelets of hamsters were activated by the in vitro addition of positive UFPs and 400-nm particles to blood. We conclude that intratracheally administered positive ultrafine and 400-nm particles induce pulmonary inflammation within 1 h. Positive UFPs, but not the 400-nm particles enhance thrombosis. Hence, particle-induced lung inflammation and thrombogenesis can be partially uncoupled.

Air Pollutants↗
PubMed2002

Ultrafine particles affect experimental thrombosis in an in vivo hamster model.

Particulate air pollution is associated with cardiovascular morbidity and mortality. To investigate this association, we studied the effect of ultrafine (60 nm) polystyrene particles on thrombus formation in a hamster model after intravenous and intratracheal administration of unmodified, carboxylate-polystyrene, or amine-polystyrene particles. Unmodified particles had no effect on thrombosis up to 5 mg/kg. Carboxylate-polystyrene particles significantly inhibited thrombus formation at 500 and 100 microg/kg body weight but not at 50 microg/kg body weight. In contrast, amine-polystyrene particles significantly enhanced thrombosis at 500 and 50 microg/kg body weight but not at 5 microg/kg body weight. Similarly, the intratracheal instillation of 5,000 microg of amine-polystyrene particles significantly increased thrombus formation. The unmodified particles and carboxylate-polystyrene particles had no effect. During platelet aggregation in human platelet-rich plasma, induced with 1.25 microM ADP, unmodified particles had no effect up to 100 microg/ml, and carboxylate-polystyrene particles weakly enhanced platelet aggregation at 25 to 100 microg/ml. However, amine-polystyrene particles (50 and 100 microg/ml) induced platelet aggregation themselves and strongly increased the ADP-induced aggregation. We conclude that the presence of (ultrafine) particles in the circulation may affect hemostasis. The observed in vivo prothrombotic tendency results, at least in part, from platelet activation by positively charged amine-polystyrene particles.

Adenosine Diphosphate↗