Particulate matter exposure induces persistent lung inflammation and endothelial dysfunction

Abstract

Epidemiologic and animal studies have shown that exposure to particulate matter air pollution (PM) is a risk factor for the development of atherosclerosis. Whether PM-induced lung and systemic inflammation is involved in this process is not clear. We hypothesized that PM exposure causes lung and systemic inflammation, which in turn leads to vascular endothelial dysfunction, a key step in the initiation and progression of atherosclerosis. New Zealand White rabbits were exposed for 5 days (acute, total dose 8 mg) and 4 wk (chronic, total dose 16 mg) to either PM smaller than 10 mum (PM(10)) or saline intratracheally. Lung inflammation was quantified by morphometry; systemic inflammation was assessed by white blood cell and platelet counts and serum interleukin (IL)-6, nitric oxide, and endothelin levels. Endothelial dysfunction was assessed by vascular response to acetylcholine (ACh) and sodium nitroprusside (SNP). PM(10) exposure increased lung macrophages (P<0.02), macrophages containing particles (P<0.001), and activated macrophages (P<0.006). PM(10) increased serum IL-6 levels in the first 2 wk of exposure (P<0.05) but not in weeks 3 or 4. PM(10) exposure reduced ACh-related relaxation of the carotid artery with both acute and chronic exposure, with no effect on SNP-induced vasodilatation. Serum IL-6 levels correlated with macrophages containing particles (P=0.043) and ACh-induced vasodilatation (P=0.014 at week 1, P=0.021 at week 2). Exposure to PM(10) caused lung and systemic inflammation that were both associated with vascular endothelial dysfunction. This suggests that PM-induced lung and systemic inflammatory responses contribute to the adverse vascular events associated with exposure to air pollution.

Cardiovascular effects of nose-only water-pipe smoking exposure in mice

“…This finding is suggestive of a bone marrow response, causing an increase in red blood cells. A consistent link between inhalation of pollutants and the bone marrow response has previously been reported, indicating a strong link between lung and systemic events (37). The elevation in erythrocytes and hematocrit observed in the present study corroborate previous findings that showed a rise of erythrocytes and hematocrit in young male smokers (18).…”

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

“…We conclude that lovastatin downregulates the PM10-induced overactive bone marrow by attenuating PM10-induced systemic inflammatory responses. polymorphonuclear leukocytes; interleukin-6 MANY WELL-DOCUMENTED STUDIES have supported the concept that ambient particulate matter (particles less than 10 m or PM 10 ) exposure induces systemic inflammatory responses, characterized by an increase in circulating proinflammatory mediators (10,22) and blood elements such as leukocytes (8, 16) or platelets (18). These systemic responses to PM 10 exposure have been implicated in the risk for downstream cardiovascular events (4).…”

“…The present study was designed to determine the effects of statins on the bone marrow of rabbits exposed to PM 10 (EHC-93). We used a well-established rabbit model of PM 10 exposure for 3 wk (6,16,22) and determined the bone marrow response by using thymidine analog, 5=-bromo-2=-deoxyuridine (BrdU) to label the dividing myeloid cells in the bone marrow. BrdU labeling enables morphological differentiation to quantify newly released PMNs from the bone marrow.…”

Sirt1 protects against thrombomodulin down-regulation and lung coagulation after particulate matter exposure

“…PM 2.5 can reach deep in the lung to the small airway and alveoli, 6 and directly cause lung inflammation and injury. [7][8][9][10][11][12][13] The pulmonary complications may lead to detrimental effects on other organs, particularly cardiovascular dysfunction such as systemic microvascular dysfunction and thrombosis. 1,2,4,5,13 A recent study demonstrated that short-term UPM exposure triggered the activation of primary hemostasis in healthy mice, with no substantial secondary hemostasis activation, leading to arterial but not venous thrombosis.…”