HIV-1 infection does not impair human alveolar macrophage phagocytic function unless combined with cigarette smoking

OBJECTIVE: Macrophages are an important reservoir for the HIV and contribute to innate lung defense by their ability to phagocytose, digest, and process invading pathogens. We hypothesized that HIV-1 infection may lead to a defect in the phagocytic activity of alveolar macrophages. DESIGN: In order to test this hypothesis, the phagocytic activity of alveolar macrophages from asymptomatic HIV-1 seropositive subjects was compared to healthy seronegative control subjects. Macrophages from one cohort were fed with Escherichia coli and from another cohort with opsonized sheep RBCs (SRBCs), and the phagocytic index was determined at different time intervals. SETTING: A tertiary-care, urban, university-based referral center. PARTICIPANTS: Asymptomatic HIV-1 seropositive subjects and healthy seropositive control subjects recruited from local community. RESULTS: No differences were found in the phagocytic activity between alveolar macrophages from the first cohort of eight seropositive and nine seronegative subjects. Although not statistically significant, there was a trend toward a lower phagocytic activity of HIV-positive smokers compared to HIV-positive nonsmokers. Opsonized phagocytic capacity (using opsonized SRBCs) was further analyzed in a second set of five HIV-positive subjects and five healthy control subjects. Whereas HIV status did not affect opsonized SRBC uptake, a history of smoking was associated with a statistically significant depression in phagocytic index. CONCLUSIONS: Although there is no significant impairment of phagocytic capacity in HIV-positive subjects compared to HIV-negative control subjects, cigarette smoking produces a significant depression in phagocytic activity that is amplified in HIV-positive smokers.     

Acute eosinophilic pneumonia induced by cigarette smoking]

The subject was a 24-year-old man who presented with acute fever, dry cough, and dyspnea. Chest X-ray films revealed diffuse infiltrates in both lungs. Bronchoalveolar lavage fluid specimens contained an increased number of eosinophils. Transbronchial lung biopsy specimens demonstrated the infiltration of eosinophils into alveolar walls and air spaces. These findings were consistent with acute eosinophilic pneumonia. The patient recovered without medical treatment. Eight days prior to admission, he had resumed smoking after 3 years of abstention. It was suggested that the cause of acute eosinophilic pneumonia in this case was associated with the resumption of smoking. To confirm that association, a smoking challenge test is usually necessary. However, similar symptoms also developed later, after the patient was passively exposed to cigarette smoke. Therefore, we concluded that smoking was probably the etiologic agent of his illness.     

SCCmecⅢ型MRSA诱导SD大鼠肺泡巨噬细胞凋亡的研究

目的研究SCCmecIII型耐甲氧西林金黄色葡萄球菌（MRSA）诱导SD大鼠肺泡巨噬细胞（AM）凋亡的能力。方法荧光显微镜和流式细胞仪分别用于观察和检测MRSA感染AM 2h、6h和12h后Annexin V-FITC/PI染色的凋亡细胞形态和凋亡率,实时荧光定量PCR（qRT-PCR）检测凋亡相关基因。结果 AM在MRSA感染后6h和12h时凋亡率与对照组相比差别均有统计学意义（P〈0.01）;感染12h时凋亡相关基因Apaf-1、caspase-9和Bax表达显著上调,Bcl-2mRNA表达显著下调（P〈0.05）。结论 MRSA可通过线粒体通路经多基因参与诱导AM凋亡;AM凋亡的研究可为MRSA肺部感染时AM凋亡分子机制的进一步研究提供基础。     

Acute eosinophilic pneumonia induced by cigarette smoking: positive lymphocyte stimulation test of a cigarette extract]

A 21-year-old man was admitted to our hospital with high fever, general fatigue and dyspnea. Chest radiography on admission showed diffuse bilateral infiltrate shadows with Kerley's B lines, and a CT scan showed patches of infiltrates with thickened interlobular septa in both lungs. Examination of the bronchoalveolar lavage fluid and the clinical course led to a diagnosis of acute eosinophilic pneumonia. The patient improved without steroid therapy. We suspected that the disease was related to smoking because the patient had started smoking seven days before the onset of the symptoms. Because a lymphocyte stimulation test gave a positive reaction to a cigarette extract, a challenge test was done. After this, the patient had fever and hypoxemia. These findings suggest that cigarette smoking induces acute eosinophilic pneumonia.     

Contribution of arginase activation to vascular dysfunction in cigarette smoking

Background

Cigarette smoke increases the risk of several cardiovascular diseases and has synergistic detrimental effects when present with other risks that contribute to its pathogenesis. Oxidative injury to the endothelium via reactive oxygen species (ROS) and nitric oxide (NO) dysregulation is a common denominator of smoking-induced alterations in vascular function. However, the mechanisms underlying ROS and NO dysregulation due to smoking remain unclear. We tested if arginase (Arg) activation/upregulation contributes to this phenomenon by constraining nitric oxide synthase (NOS) activity.

Methods

Arg2 knockout (Arg2^−/−) and control C57BL/6J mice were either exposed to cigarette smoke, 6 h/day/2 weeks (Second Hand Smoking; SHS) or housed in normal environment (Non Smoking; NS). Arg activity, NO and ROS levels were determined by measuring urea production, fluorescent dye (DAF), and dihydroethedium (DHE) respectively in isolated mouse aorta.

Results

Arg activity and ROS levels were higher NO lower in SHS compared to NS mice. SHS failed to lower NO levels in Arg2^−/− mice. Endothelial dependent vasodilation (EDV) was attenuated in SHS mice as compared to controls (78.80% ± 8 vs 46.58% ± 5). This impaired EDV was abolished in Arg2^−/− mice (67.48% ± 7 in SHS vs. 78.80% ± 8 in NS). Vascular stiffness was increased in SHS mice as compared to NS controls but remained unchanged in Arg2^−/− mice.

Conclusion

Endothelial NOS is uncoupled by smoking exposure, leading to endothelial dysfunction and vascular stiffness, a process that is prevented by Arg2 deletion. Hence, we identify Arg2 upregulation as a critical pathogenic factor and target for therapy in oxidative injury following smoking exposure through reciprocal regulation of endothelial NOS.     

Unconjugated pteridines in bronchoalveolar lavage as indicators of alveolar macrophage activation

Bronchoalveolar lavage (BAL) has shown great efficacy in clarifying the role of immune processes in many disorders of the lower respiratory tract. Following the in vitro demonstration that neopterin is an indicator of the activation of macrophages, neopterin was measured in the BAL fluid and cells from patients with various pulmonary diseases. In most of the patients, high levels of neopterin were found in the serum, BAL fluid and BAL cells. Because neopterin in BAL fluid results from local production as well as from plasma transudation, neopterin in BAL cells seems to reflect the macrophage stimulation more directly. In addition, the correlation between cellular neopterin and lymphocyte count was found to be more significant than the correlation between cellular neopterin and macrophage count. Neopterin in BAL fluid and cells may be a useful measurement in the investigation and elucidation of pulmonary pathologies involving the cellular immune system.     

Acute eosinophilic pneumonia caused by cigarette smoking

It has been suggested that acute eosinophilic pneumonia (AEP) is associated with cigarette smoking because in Japan, the patients with AEP are young and have a high incidence of short-term smoking history. However, there has been no direct evidence to support that cigarette smoke causes AEP. Herein is reported the first case showing the direct evidence and a long-term clinical course of cigarette smoking-induced AEP, in which tolerance to repeated resumption of smoking cigarettes might have occurred. We should pay attention to the history of cigarette smoking in seeing patients with AEP, especially in young patients.     

Correlated effects of cigarette smoke components on alveolar macrophage adenosine triphosphatase activity and phagocytosis.

An initial examination was made of the hypothesis that one action of cigarette smoke components on pulmonary alveolar macrophage function involves the inhibition of contractile protein adenosine triphosphatase activity. Pulmonary alveolar macrophage calcium-dependent adenosine triphosphatase activity, magnesium-dependent adenosine triphosphatase activity, sodium-potassium-dependent adenosine triphosphatase activity, phagocytosis, and cell adhesiveness were measured in the presence of cigarette smoke, acrolein, ouabain, and ethacrynic acid. Calcium-dependent adenosine triphosphatase activity, magnesium-dependent adenosine triphosphatase activity, phagocytosis, and adhesiveness were inhibited by smoke and ethacrynic acid, but not by ouabain. Acrolein, a component of smoke, inhibited phagocytosis, adhesiveness, and calcium-dependent adenosine triphosphatase activity, indicating that another component of smoke must be effective at inhibiting magnesium-dependent adenosine triphosphatase activity. Sodium-potassium-dependent adenosine triphosphatase activity was inhibited by ouabain and ethacrynic acid, but not by smoke or acrolein. Finally, sulfhydryl reagents at least partially protected the macrophages against the inhibitory actions of each of the agents. The results are in accord with recently obtained experimental evidence that calcium-dependent adenosine triphosphatase and, perhaps, magnesium-dependent adenosine triphosphatase play a role in phagocytosis. The data also suggest that smoke components affect a number of macrophage activities, including adhesion and phagocytosis, by altering the cell's contractile apparatus.     

Delay discounting by adolescents experimenting with cigarette smoking

Aims To evaluate delay discounting and self‐reported impulsive behavior in a sample of adolescents experimenting with cigarette smoking compared with adolescents who had never smoked or were daily smokers. Design A cross‐sectional design was used to compare smoking‐status groups. Setting Columbus, Ohio, a city of approximately 780 000 people. Participants A sample of 141 male and female adolescents with a mean age of 15.37 (standard deviation = 1.09) years. Measurements Primary measures included a computerized assessment of delay discounting, a self‐report assessment of impulsivity [Barratt Impulsiveness Scale—adolescent (BIS‐11‐A)] and verifications of cigarette smoking status (breath carbon monoxide and urinary cotinine level). Findings Smokers discounted more by delay and had higher impulsivity scores than non‐smokers. Experimenters had scores intermediate to those of smokers and non‐smokers on both measures. In some analyses the difference between experimenters and non‐smokers was significant, with experimenters showing greater delay discounting, but in no case did experimenters differ significantly from the smokers. Conclusions Young people who experiment with cigarettes appear to be similar to those who smoke regularly in terms of tendency to discount future gains and report impulsive tendencies, and generally higher in these traits than non‐smokers.     

Association between alveolar macrophage plasminogen activator activity and indices of lung function in young cigarette smokers

Recent evidence suggests that connective tissue breakdown in the human lung leading to airway obstruction and emphysema involves proteinases expressed by neutrophils and macrophages that traffic to the lungs in response to cigarette smoke. It remains unclear why only a small fraction of all cigarette smokers develop symptomatic airway obstruction. In this study, we examined indexes of inflammation and proteolytic activity in samples of bronchoalveolar lavage from young cigarette smokers and questioned whether there was any correlation between the extent of inflammation or enzymatic activity and lung function. A total of 125 apparently healthy community volunteers who currently smoked at least one pack per day were evaluated by spirometry. Seven subjects with a relatively low FEV1/FVC (% predicted) were identified and further studied by bronchoalveolar lavage. These were compared with a group of 10 smokers of similar age (mean age, 33 yr) and pack-years and higher FEV1/FVC (% predicted). Both groups showed increased accumulation of lung macrophages and neutrophils as compared to nonsmokers, but there were no differences in total cells or cellular differentials between the groups. Similarly, there were no differences in either alveolar fluid phase elastase, antielastase, and plasminogen activator (PA) activities or macrophage elastolytic activity between the groups. In contrast, there was a clear difference in macrophage plasminogen activator activity between the groups, cells from the group with a lower FEV1/FVC (% predicted) having a higher PA activity than that of macrophages from the group with higher FEV1/FVC (% predicted), i.e., 0.50 +/- 0.16 international urokinase units/10(6) cells versus 0.30 +/- 0.10 units/10(6) cells (p less than 0.0007).(ABSTRACT TRUNCATED AT 250 WORDS)     

羟基红花黄色素A对香烟提取物诱导A549细胞炎症因子表达作用的研究

目的:探讨羟基红花黄色素A(HSYA)抑制香烟烟雾提取物(CSE)诱导的A549肺泡上皮细胞炎症介质表达升高的作用。方法:用CSE刺激A549肺泡上皮细胞建立损伤模型,细胞分七组:单纯HSYA组、Sham组、CSE组、CSE+HSYA低剂量组(1μmol/L)、CSE+HSYA中剂量组(4μmol/L)、CSE+HSYA高剂量组(16μmol/L)和CSE+阳性对照药红霉素(5μg/mL)组。以RT-qPCR技术检测白介素(IL)-6、白介素(IL)-1β、肿瘤坏死因子(TNF)-α、细胞间黏附分子(ICAM)-1和血管细胞黏附分子(VCAM)-1 mRNA的表达水平;ELISA法检测细胞培养液中IL-6、IL-1β及TNF-α的蛋白水平表达;蛋白质印迹法(western blot)检测细胞p38MAPK磷酸化的水平。结果:与Sham组相比,CSE组IL-6、IL-1β、TNF-α、ICAM-1和VCAM-1 mRNA水平均明显升高(P0.001),给予不同浓度的HSYA后炎症因子的高表达受到抑制,红霉素组也见较明显的抑制。与Sham组相比,CSE组细胞上清液中IL-6、IL-1β和TNF-α蛋白的表达水平明显升高(P0.001),给予不同浓度的HSYA后CSE所诱发的炎症因子的高表达受到抑制,红霉素组也见较明显的抑制。与Sham组比较,CSE组的p38 MAPK的磷酸化水平明显升高(P0.001),给予不同浓度的HSYA后细胞p38 MAPK的磷酸化水平升高受到抑制,红霉素组也可见明显的抑制。结论:HSYA可抑制CSE诱导A549细胞的炎症因子的表达升高。     

A single high dose of vitamin C counteracts the acute negative effect on microcirculation induced by smoking a cigarette.

Cigarette smoking is associated with marked acute changes in microcirculation including reduced blood flow. We tested the hypothesis that the reduced blood flow velocity is due to the imbalance between prooxidants and antioxidants that occurs as a consequence of smoking and that it can be reduced by an antioxidant. The effect of smoking a single cigarette on nail-fold microcirculation was analyzed in 24 healthy subjects with varying smoking habits. Vital capillary microscopy was used and the blood cell flow velocity in the capillaries was evaluated before and 1-30 min after smoking. Smoking induced a marked decrease in microcirculatory blood flow in 23 of the 24 subjects (40-50% decrease 1-5 min after smoking). This change was reduced by more than 50% in the same subjects after intake of 2 g of vitamin C 2 h before smoking (P < 0.0001 by ANOVA test) with smokers responding similarly to nonsmokers in these experiments. Intake of 1 g of vitamin C had no significant effect on the smoking-induced changes in most of the subjects tested (n = 11). Pretreatment with aspirin had little or no effect on the response to smoking (n = 9). Our results show that treatment with a single high dose of vitamin C can reduce and in some individuals even completely abolish the negative acute effect on microcirculation induced by smoking a single cigarette. This effect of vitamin C is not likely to be mediated by the cyclooxygenase system.