Of the several factors believed to exacerbate asthmatic symptoms, air pollution and viral infections are considered to be particularly important. Although evidence indicates that each of these respiratory insults individually can increase asthma severity in susceptible individuals, we know little about the extent to which exposure to environmental oxidant pollutants can influence the course of respiratory viral infection and its associated inflammation. To investigate the interaction of these two stimuli within their common epithelial cell targets in the upper and lower respiratory tracks, we infected primary human nasal epithelial cells and cells of the BEAS-2B line grown at the air-liquid interface with human rhinovirus type 16 (RV16) and exposed them to NO2 (2.0 ppm) or O3 (0.2 ppm) for 3 hr. Independently, RV16, NO2, and O3 rapidly increased release of the inflammatory cytokine interleukin-8 through oxidant-dependent mechanisms. The combined effect of RV16 and oxidant ranged from 42% to 250% greater than additive for NO2 and from 41% to 67% for O3. We abrogated these effects by treating the cells with the antioxidant N-acetylcysteine. Surface expression of intercellular adhesion molecule 1 (ICAM-1) underwent additive enhancement in response to combined stimulation. These data indicate that oxidant pollutants can amplify the generation of proinflammatory cytokines by RV16-infected cells and suggest that virus-induced inflammation in upper and lower airways may be exacerbated by concurrent exposure to ambient levels of oxidants commonly encountered the indoor and outdoor environments.

The vesicular monoamine transporter 2 (VMAT2, SLC18A2) takes up cytosolic monoamines into intracellular secretory vesicles, preventing their neurotoxicity in the cytosol and discharging them into extracellular space by exocytosis. It has been shown that one-copy deletion of the VMAT2 gene increases locomotion activity significantly in response to drug treatments and dopamine neuron death rate in response to neurotoxin treatments in knockout mice. Little is known about promoter polymorphisms and their influence on SLC18A2 promoter activity. We have re-sequenced a 17.4 kb DNA in the SLC18A2 promoter region for Caucasians and revealed 47 polymorphisms that confer 13 haplotypes. One of the haplotypes reaches a frequency as high as 65%, likely due to positive selection. In vitro analysis showed a 20% difference in promoter activity between two frequent haplotypes and identified some of the polymorphisms that influence promoter activity. Four haplotype-defining single nucleotide polymorphisms (hdSNPs) can define the frequent haplotypes and by genotyping these hdSNPs, we find that haplotypes with -14234G and -2504C of SLC18A2 promoter region represent a protective factor against alcoholism (P = 0.0038 by Fisher's exact tests). Therefore, SLC18A2 promoter haplotypes defined here create a foundation for transcriptional characterization of individuality and for association study on monoamine-related human diseases.

Difference between arch diameter and true lumen diameter in the descending aorta was studied in patients with type B aortic dissection. The diameters of the aortic arch (Proximal ) and mid-descending aorta (Distal ) were measured on computer tomography angiography (CTA) in 20 healthy adults. Forty-two patients with type B aortic dissection who underwent endovascular repair were divided into two groups: an acute group (23 patients) and a chronic group (19 patients). The diameters of the arch (Proximal ) and the true lumen of the mid-descending aorta (Distal ) were measured on digital subtraction angiography (DSA) and CTA. The taper ratio was defined as (Proximal -Distal )/(Proximal )x100%. In the control group, the taper ratio was 13.0+/-4.7% on CTA. In the acute patients group, the taper ratio was 23.6+/-11.3% on DSA and 21.9+/-12.1% on CTA. In the chronic patients group, the taper ratio was 31.5+/-13.6% on DSA and 30.1+/-11.4% on CTA. In both acute and chronic type B aortic dissection, the aorta tapers significantly from arch to true lumen in the descending aorta. Stent-graft with tapered design may be a viable treatment option for endovascular repair of type B aortic dissection.

Epithelial cells of the human respiratory tract express human leukocyte antigen (HLA) and the costimulatory molecules B7-1 and B7-2. Little is known, however, about the constitutive expression of genes encoding for the more recently identified members of the B7 homolog family of costimulatory molecules or about the influence of cellular differentiation and cytokines on their activity or on that of HLA or B7-1 and B7-2. Human nasal epithelial (HNE) cells were grown at the air-liquid interface (ALI) for 2 or 21 days to model in vivo conditions. Expression of genes for HLA-B and HLA-DR1 increased during mucociliary differentiation during this period and became more similar to HNE cells obtained fresh by brush biopsy from nasal turbinates. Gene transcripts for B7-H3 and B7-H2 were abundantly expressed in cells cultured at the ALI, but neither their activities nor that of B7-2 was significantly altered during differentiation. IFN-gamma and TNF-alpha upregulated mRNA encoding for both HLA molecules, but not for the B7 molecules. This study describes, for the first time, the expression of B7-H3 and B7-H2 by HNE cells and thus expands the range of potential costimulatory signals through which these cells may interact with activated mucosal T lymphocytes. In addition, the results suggest that the extent of mucociliary differentiation of cultured cells may influence this capability

Primary human epithelial cells obtained from the middle meatus express genes associated with antigen presentation function. The pattern of gene expression is modulated by cytokine stimulation and changes as the cells differentiate at the ALI. These findings suggest that mature middle meatal epithelial cells have the cellular machinery to interact with T cells and therefore may be direct participants in the modulation of T-cell activity in chronic sinusitis.

Bronchial epithelial cells provide a functional barrier to the movement of water and solutes between the luminal and interstitial compartments of the lung. Barrier integrity can be compromised by a variety of factors, including polycationic proteins released by inflammatory cells. We investigated the characteristics of epithelial barrier function and its modulation by cationic stimuli in canine bronchial epithelial (CBE) cells grown in culture. Morphologic characteristics were examined, and barrier function was assessed by measurements of transepithelial mannitol flux (flux) and electrical resistance (RT) during a stable, 3- to 14-day culture period. CBE cultures exhibited progressive mucociliary differentiation and contained nonciliated, ciliated, and neutral and acidic mucin-secretory cells. The synthetic polycation, poly-L-lysine (PLL), from 2.5 to 10 micrograms/ml, caused dose-related increases in flux and decreases in RT that were not accompanied by detectable release of lactate dehydrogenase (LDH) or changes in histochemical appearance. The effect on RT spontaneously reversed over a 15-h recovery period. The action of PLL on flux was not attenuated by treatment of the cells to stabilize cytoskeletal contractile elements but was immediately attenuated by the addition of heparin to the challenged cells. These results indicate that modulation of the barrier integrity of bronchial epithelial cells by cationic proteins, such as those released by inflammatory cells, represents a physiologic process that may be regulated by endogenous anionic factors.

SBP/DBP, (Cardiol J 2016; 23, 4: 473-481)

This study was undertaken to determine the relationship of soluble intercellular adhesion molecule 1 (sICAM-1) levels in bronchoalveolar lavage (BAL) fluid during allergic airway inflammation to those in the vascular compartment and to cellular components in the BAL fluids. A group of 11 allergic subjects underwent initial bronchoscopy during which a control BAL was performed and normal saline (NS) and specific antigen (Ag) were administered to two sublobar segments. A second bronchoscopy was performed 17 to 21 h later, and the NS and Ag segments were lavaged. Blood was drawn before each bronchoscopic procedure. The mean concentration of sICAM-1 in BAL fluid from NS-challenged segments was 59.2 +/- 7.6 ng/ml and was not different from that in unchallenged segments (51.5 +/- 5.6 ng/ml). In BAL fluid from Ag-challenged segments, mean concentrations of sICAM-1 increased significantly to 97.5 +/- 12.5 ng/ml. Segmental antigen challenge was associated with a small but statistically significant increase in sICAM-1 concentrations in serum. The concentrations of sICAM-1 in BAL fluid after antigen challenge exceeded levels that could be accounted for by passive transudation from the circulation, based upon the magnitude of increases in BAL albumin concentrations. The levels of sICAM-1 in BAL from Ag-challenged segments were correlated significantly with the total white cell, lymphocyte, neutrophil, and eosinophil counts in BAL fluids. These results are supportive of the notion that the local release of sICAM-1 may play a role in allergen-induced inflammatory processes in the airways.