scholarly journals Delayed neonatal lung macrophage differentiation in a mouse model of in utero ethanol exposure

2010 ◽  
Vol 299 (1) ◽  
pp. L8-L16 ◽  
Author(s):  
Theresa W. Gauthier ◽  
Xiao-Du Ping ◽  
Levan Gabelaia ◽  
Lou Ann S. Brown

We have previously demonstrated that fetal ethanol exposure deranges the function and viability of the neonatal alveolar macrophage. Although altered differentiation of the alveolar macrophage contributes to pulmonary disease states within the adult lung, the effects of fetal ethanol exposure on the normal differentiation of interstitial to alveolar macrophage in the newborn lung are unknown. In the current study, using a mouse model of fetal ethanol exposure, we hypothesized that altered terminal differentiation of the neonatal interstitial to alveolar macrophage contributes to the observed cellular dysfunction in the ethanol-exposed newborn mouse. Control alveolar macrophage differentiation was characterized by increased expression of CD32/CD11b ( P ≤ 0.05) and increased in vitro phagocytosis of Staphylococcus aureus ( P ≤ 0.05) compared with interstitial macrophage. After in utero ethanol exposure, both alveolar and interstitial macrophage lacked the acquisition of CD32/CD11b ( P ≤ 0.05) and displayed impaired in vitro phagocytosis ( P ≤ 0.05). Ethanol significantly increased transforming growth factor-β1(TGF-β1) in the bronchoalveolar lavage fluid ( P ≤ 0.05), as well as in both interstitial and alveolar macrophages ( P ≤ 0.05). Oxidant stress contributed to the ethanol-induced changes on the interstitial and alveolar cells, since maternal supplementation with the glutathione precursor S-adenosylmethionine during ethanol ingestion normalized CD32/CD11b ( P ≤ 0.05), phagocytosis ( P ≤ 0.05), and TGF-β1in the bronchoalveolar lavage fluid and macrophages ( P ≤ 0.05). Contrary to our hypothesis, fetal ethanol exposure did not solely impair interstitial to alveolar macrophage differentiation. Rather, fetal ethanol exposure impaired both neonatal interstitial and alveolar macrophage phagocytic function and differentiation. Increased oxidant stress and elevated TGF-β1contributed to the impaired differentiation of both interstitial and alveolar macrophage.

Cytokine ◽  
2013 ◽  
Vol 63 (2) ◽  
pp. 194-200 ◽  
Author(s):  
Seigo Okada ◽  
Shunji Hasegawa ◽  
Hideki Hasegawa ◽  
Akira Ainai ◽  
Ryo Atsuta ◽  
...  

Toxics ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 40
Author(s):  
Taisuke Tomonaga ◽  
Hiroto Izumi ◽  
Chinatsu Nishida ◽  
Kaori Kato ◽  
Kazuhiro Yatera ◽  
...  

Photocatalytic filters installed in air purifiers have been used to purify spaces by decomposing allergenic substances. However, we have not found any reports that evaluate the effectiveness of photocatalytic filters in suppressing allergic reactions in living organisms. In this study, we intratracheally instilled ovalbumin (OVA) into OVA-sensitized mice after the OVA was photocatalyzed by a titanium dioxide (TiO2) filter, and verified the experimental model for evaluating the allergy-suppressing effect of photocatalysts. Mice were sensitized to OVA (10 µg/mouse) four times, and were intratracheally instilled with OVA (10 µg/mouse) after photocatalysis three times. Non-sensitized animals were instilled with normal saline following the same exposure schedule. The mice were dissected 24 h after final exposure. The OVA after photocatalysis significantly decreased the number of eosinophils in bronchoalveolar lavage fluid, and the concentration of OVA-specific IgE and IgG1 in serum, which were elevated in untreated OVA. Moreover, our experimental model showed the suppression of allergic reactions in mice, along with the decomposition of OVA after photocatalysis using the photocatalytic filter. Taken together, our experimental model for evaluating allergic reactions in the respiratory tract suggested that the allergy-suppressing effect of the photocatalytic filter can be evaluated.


2011 ◽  
Vol 300 (1) ◽  
pp. L139-L147 ◽  
Author(s):  
Foula Sozo ◽  
Melissa Vela ◽  
Victoria Stokes ◽  
Kelly Kenna ◽  
Peter J. Meikle ◽  
...  

Prenatal ethanol exposure increases collagen deposition and alters surfactant protein (SP) expression and immune status in lungs of near-term fetal sheep. Our objectives were to determine 1) whether these prenatal effects of repeated gestational ethanol exposure persist after birth and 2) whether surfactant phospholipid composition is altered following prenatal ethanol exposure. Pregnant ewes were chronically catheterized at 90 days of gestational age (DGA) and given a 1-h daily infusion of ethanol (0.75 g/kg, n = 9) or saline ( n = 7) from 95 to 135 DGA; ethanol administration ceased after 135 DGA. Lambs were born naturally at full term (146 ± 0.5 DGA). Lung tissue was examined at 9 wk postnatal age for alterations in structure, SP expression, and inflammation; bronchoalveolar lavage fluid was examined for alterations in surfactant phospholipid composition. At 134 DGA, surfactant phospholipid concentration in amniotic fluid was significantly reduced ( P < 0.05) by ethanol exposure, and the composition was altered. In postnatal lambs, there were no significant differences between treatment groups in birth weight, postnatal growth, blood gas parameters, and lung weight, volume, tissue fraction, mean linear intercept, collagen content, proinflammatory cytokine gene expression, and bronchoalveolar lavage fluid surfactant phospholipid composition. Although SP-A, SP-B, and SP-C mRNA levels were not significantly different between treatment groups, SP-D mRNA levels were significantly greater ( P < 0.05) in ethanol-treated animals; as SP-D has immunomodulatory roles, innate immunity may be altered. The adverse effects of daily ethanol exposure during late gestation on the fetal lung do not persist to 2 mo after birth, indicating that the developing lung is capable of repair.


Medicina ◽  
2010 ◽  
Vol 46 (5) ◽  
pp. 315 ◽  
Author(s):  
Agnė Babušytė ◽  
Jolanta Jeroch ◽  
Rimantas Stakauskas ◽  
Kristina Stravinskaitė ◽  
Kęstutis Malakauskas ◽  
...  

Objective. The aim of study was to investigate a chemotactic effect of induced sputum and bronchoalveolar lavage fluid on blood neutrophils in patients with chronic obstructive pulmonary disease (COPD) and healthy individuals. Material and methods. Forty-three smokers with COPD, 19 ex-smokers with COPD, 13 healthy smokers, and 17 healthy nonsmokers were recruited to the study. Neutrophils were isolated from peripheral blood of study individuals. For the same experimental conditions, pooled induced sputum and bronchoalveolar lavage fluid of 20 COPD patients were used. Neutrophil chemotaxis in vitro was performed in cell-transmigration chamber. Substances tested for chemoattraction (interleukin-8, induced sputum, bronchoalveolar lavage fluid directly or in addition to interleukin-8) were added to lower wells. Upper wells were filled with 2.5×106/mL of neutrophil culture and incubated for 2 hours. Migration was analyzed by flow cytometry. Results. Interleukin-8 (10–100 ng/mL) induced a dose-dependant neutrophil migration in all the groups. Only 100 ng/L of interleukin-8 induced more intensive chemotaxis of neutrophils from COPD smokers as compared to ex-smokers (P<0.05). Such difference between healthy individuals was obtained using 30 ng/mL of interleukin-8 (P<0.05). Induced sputum/interleukin-8 (10–100 ng/mL), as well as induced sputum directly, induced neutrophil migration (P<0.05). Chemotaxis of neutrophils isolated from COPD patients and healthy nonsmokers did not depend on additional interleukin-8 concentration. Bronchoalveolar lavage fluid/interleukin-8 (30–100 ng/mL) induced more intensive migration of neutrophils from COPD patients than bronchoalveolar lavage fluid (P<0.05) alone. Conclusions. Migration of neutrophils isolated from patients with COPD was more intensive compared to healthy individuals. Induced sputum and bronchoalveolar lavage fluid directly and with addition of interleukin-8 stimulated chemotaxis, and it was higher in neutrophils from COPD patients. Migration of neutrophils did not depend on smoking status.


2013 ◽  
Vol 57 (8) ◽  
pp. 3883-3888 ◽  
Author(s):  
Koichi Yamada ◽  
Katsunori Yanagihara ◽  
Norihito Kaku ◽  
Yosuke Harada ◽  
Yohei Migiyama ◽  
...  

ABSTRACTAcinetobacter baumanniiis one of the main pathogens that cause ventilator-associated pneumonia (VAP) and is associated with a high rate of mortality. Little is known about the efficacy of macrolides againstA. baumannii. In order to confirm the efficacy of azithromycin (AZM) against VAP caused by multidrug-resistantA. baumannii(MDRAB), we used a mouse model that mimics VAP by placement of a plastic tube in the bronchus. AZM (10 and 100 mg/kg of body weight) was administered subcutaneously every 24 h beginning at 3 h after inoculation. Phosphate-buffered saline was administered as the control. Survival was evaluated over 7 days. At 48 h postinfection, mice were sacrificed and the numbers of viable bacteria in lungs and bronchoalveolar lavage fluid were compared. Histopathological analysis of lung specimens was also performed. The treatment groups displayed significantly longer survival than the control group (P< 0.05). AZM did not have an antimicrobial effect. Histopathological examination of lung specimens indicated that the progression of lung inflammation was prevented in the AZM-treated groups. Furthermore, total cell and neutrophil counts, as well as cytokine levels, in bronchoalveolar lavage fluid were significantly decreased (P< 0.05) in the AZM-treated groups. AZM may have a role for the treatment of VAP with MDRAB because of its anti-inflammatory effects.


mBio ◽  
2012 ◽  
Vol 4 (1) ◽  
Author(s):  
Ousmane H. Cissé ◽  
Marco Pagni ◽  
Philippe M. Hauser

ABSTRACTPneumocystis jiroveciiis a fungus that causes severe pneumonia in immunocompromised patients. However, its study is hindered by the lack of anin vitroculture method. We report here the genome ofP. jiroveciithat was obtained from a single bronchoalveolar lavage fluid specimen from a patient. The major challenge was thein silicosorting of the reads from a mixture representing the different organisms of the lung microbiome. This genome lacks virulence factors and most amino acid biosynthesis enzymes and presents reduced GC content and size. Together with epidemiological observations, these features suggest thatP. jiroveciiis an obligate parasite specialized in the colonization of human lungs, which causes disease only in immune-deficient individuals. This genome sequence will boost research on this deadly pathogen.IMPORTANCEPneumocystispneumonia is a major cause of mortality in patients with impaired immune systems. The availability of theP. jiroveciigenome sequence allows new analyses to be performed which open avenues to solve critical issues for this deadly human disease. The most important ones are (i) identification of nutritional supplements for development of culturein vitro, which is still lacking 100 years after discovery of the pathogen; (ii) identification of new targets for development of new drugs, given the paucity of present treatments and emerging resistance; and (iii) identification of targets for development of vaccines.


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