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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 rag) to either PM smaller than 10 [micro]m ([PM.sub.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.sub.10] exposure increased lung macrophages (P < 0.02), macrophages containing particles (P < 0.001), and activated macrophages (P < 0.006). [PM.sub.10] increased serum IL-6 levels in the first 2 wk of exposure (P < 0.05) but not in weeks 3 or 4. [PM.sub.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.sub.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. air pollution; alveolar macrophage; systemic inflammation; interleukin-6

Epidemiologic studies have shown an association between exposure to ambient particulate air pollution atherosclerosis; adhesion molecules

Inflammation accelerates polymorphonuclear leukocyte (PMN) release from the bone marrow, and these PMNs are implicated in inappropriate tissue injury. We have previously developed a method using 5'-bromo-2'deoxyuridine (BrdU) to study PMN kinetics using an immunocytochemical grading system of PMN on cytospin slides. The aim of this study was to develop a flow cytometric method to quantify the number of positively stained PMN and grade the intensity of staining for the transit time calculation of PMN through the marrow. Dividing myeloid progenitors in the marrow of rabbits were labeled with a pulse dosage of intravenous BrdU. BrdU-labeled PMN ([PMN.sup.BrdU]) were detected in the circulation using a FITC-conjugated anti-BrdU monoclonal antibody. The [PMN.sup.BrdU] were assigned to five groups according to their FITC intensity, and the transit times of PMN at different stages of development in the marrow were calculated. Results were compared using parallel immunocytochemical analysis of the same samples. In control animals, [PMN.sup.BrdU] in the circulation peaked at 72 h after BrdU labeling with 36.0% of PMN labeled. In normal rabbits, the transit times of PMN through the mitotic pool (49.5 [+ or -] 4.2 h) and maturation pool (65.5 [+ or -] 3.1 h) correlated well with immunocytochemical analysis and previously published values. Using this method, we demonstrated that exposure to air pollution particles accelerates the release of [PMN.sup.BrdU] from the marrow. We conclude that a flow cytometric approach for identifying BrdU-labeled leukocytes provides an objective and accurate method for studying leukocyte kinetics and behavior. polymolphonuclear neutrophil; flow cytometry; transit time

Inhalation exposure to particles < 10 [micro]m in size that are suspended in the troposphere (P[M.sub.10]) is a factor in respiratory and cardiovascular diseases. The extent of the injury, local to systemic inflammation, is dependent on the number, size, and composition of the particles to which an individual is exposed. The physical properties of and compounds on P[M.sub.10] that are responsible for these adverse effects on human health are the subject of intense investigation. Here, we report a laboratory method that involved the creation of 1-120 particles per trial that were of known size and composition, followed by deposition of them directly onto individual human lung cells within a cell culture, and after an incubation period, a downstream biological response was measured. To illustrate this methodology, particles that each contained 50 pg of lipopolysaccharide were created and deposited onto individual cells over a region

Alveolar macrophages (AM) play a key role in clearing atmospheric particulates from the lung surface and stimulating epithelial cells to produce proinflammatory mediators. The present study examines the role of 'acute response' cytokines TNF-[alpha] and IL-1[beta] released by AM exposed to ambient particulate matter with a diameter of 0.05), and the combination of the two antibodies most effective. When HBEC were treated similarly, anti-TNF-[alpha] antibodies had the greatest effect. In A549 cells P[M.sub.10]-exposed AM supernatants increased NF-[kappa]B, activator protein (AP)-1 and specificity protein 1 binding, while anti-TNF-[alpha] and anti-IL-1[beta] antibodies reduced NF-[kappa]B and AP-1 binding. We conclude that AM-derived TNF-[alpha] and IL-1[beta] provide a major stimulus for the production of proinflammatory mediators by lung epithelial cells and that their relative importance may depend on the type of epithelial cell target. ribonuclease protection assay; transcription factors; enzyme-linked immunosorbent assay; proinflammatory mediators; particulate matter with diameter < 10 [micro]m

Exposure to air pollution [particulate matter, particles air pollution; alveolar macrophages; atherosclerosis; inflammation; leukocytes

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 ([MO.sup.BrdU]), and their release into the blood and disappearance from the circulation were monitored using a double immunostaining method. The first [MO.sup.BrdU] appeared in the circulation 4 h after labeling with BrdU and peaked at 18 h when 34.3 [+ or -] 5.8% of monocytes were labeled. The calculated transit time of monocytes through bone marrow was 38.1 [+ or -] 3.1 h in control rabbits with a half-life ([T.sub.1/2]) 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 [+ or -] 1.8 vs. 22.6 [+ or -] 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. leukocytes; transit time; half life; pneumonia; rabbits

We examined the hypothesis that ambient particulate matter with a diameter of interleukin-8; monocyte chemoattractant protein-1; intercellular adhesion molecule-1; nuclear factor-[kappa]B; transcription factor specificity protein 1; particulate matter

Interleukin-6 (IL-6) shortens the transit time of polymorphonuclear leukocytes (PMN) through the marrow and accelerates their release into the circulation. In contrast to other inflammatory stimuli, this response is associated with a decrease in L-selectin levels on circulating PMN. The present study was designed to determine the effect of IL-6 on L-selectin levels of PMN in rabbits. Recombinant human IL-6 (2 [micro]g/kg) caused a decrease in L-selectin levels on circulating PMN 3 to 12 h after treatment (P < 0.05). L-selectin levels decreased on PMN already in the circulation for up to 4 h (P < 0.05), on PMN released from the marrow posttreatment for up to 12 h (P < 0.01) and on PMN in the marrow for up to 6 h (P < 0.05) after IL-6 treatment. We conclude that IL-6 decreases L-selectin levels on circulating PMN by demarginating PMN with low levels of L-selectin and by releasing PMN from the marrow with low levels of L-selectin. We postulate that this prolonged downregulation of L-selectin on circulating PMN could influence their recruitment into inflammatory sites. cytokine; bone marrow; neutrophil

Experiments were performed to investigate the migration of polymorphonuclear leukocytes (PMN) or neutrophils from the bone marrow into the lung tissue succeeding bacteremic infection. The bone marrow release and sequestration of PMNs during a focal subcutaneous infection were measured using immunohistochemistry. Granulocytopenia was observed following the infection and was attributed to the release of younger and immature PMNs in the circulation.

The transit times of polymorphonuclear leukocytes (PMN) in the mitotic and postmitotic pools of rabbit bone marrow (BM) were analyzed by utilizing 5'-bromo-2'-deoxyuridine thymidine analogues. The total PMN transit time in rabbit BM is 95 hours. PMN transit time in the mitotic pools of the BM is 51 hours while the PMN transit time in the postmitotic or maturation pool is 65 hours. However, the local pneumonic process decreases the transit time in the mitotic and maturation pools indicating the role of PMN in the pathogenesis of lung injury.

Background: People with human immunodeficiency virus (PWH) have an increased risk of developing chronic obstructive pulmonary disease (COPD).Methods: We phenotyped lung macrophages in 4 subgroups-M1 (CD40+CD163-), M2 (CD40-CD163+), double positives (CD40+CD163+), and double negatives and (CD40-CD163-)-and we determined their phagocytic capacity in PWH with and without COPD.Results: People with human immunodeficiency virus with COPD have more double-negative macrophages (84.1%) versus PWH without (54.3%) versus controls (23.9%) (P=.004) and reduced phagocytosis (P=.012). Double-negative macrophages had the worst phagocytic capacity (P<.001).Conclusions: People with human immunodeficiency virus with COPD have an abundance of nonpolarized macrophages, which have poor phagocytic capacity and therefore predispose PWH to increased risk of disease progression. [ABSTRACT FROM AUTHOR]