The inhalation of metal (including lead) nanoparticles poses a real health issue to people and animals living in polluted and/or industrial areas. In this study, we exposed mice to lead(II) nitrate nanoparticles [Pb(NO3)2 NPs], which represent a highly soluble form of lead, by inhalation. We aimed to uncover the effects of their exposure on individual target organs and to reveal potential variability in the lead clearance. We examined (i) lead biodistribution in target organs using laser ablation and inductively coupled plasma mass spectrometry (LA-ICP-MS) and atomic absorption spectrometry (AAS), (ii) lead effect on histopathological changes and immune cells response in secondary target organs and (iii) the clearance ability of target organs. In the lungs and liver, Pb(NO3)2 NP inhalation induced serious structural changes and their damage was present even after a 5-week clearance period despite the lead having been almost completely eliminated from the tissues. The numbers of macrophages significantly decreased after 11-week Pb(NO3)2 NP inhalation; conversely, abundance of alpha-smooth muscle actin (α-SMA)-positive cells, which are responsible for augmented collagen production, increased in both tissues. Moreover, the expression of nuclear factor κB (NF-κB) and selected cytokines, such as tumor necrosis factor alpha (TNFα), transforming growth factor beta 1 (TGFβ1), interleukin 6(IL-6), IL-1α and IL-1β , displayed a tissue-specific response to lead exposure. In summary, diminished inflammatory response in tissues after Pb(NO3)2 NPs inhalation was associated with prolonged negative effect of lead on tissues, as demonstrated by sustained pathological changes in target organs, even after long clearance period.
- MeSH
- aktiny agonisté genetika imunologie MeSH
- alveolární makrofágy účinky léků imunologie patologie MeSH
- aplikace inhalační MeSH
- biologická dostupnost MeSH
- dusičnany farmakokinetika toxicita MeSH
- exprese genu MeSH
- inhalační expozice analýza MeSH
- interleukin-1alfa agonisté genetika imunologie MeSH
- interleukin-1beta agonisté genetika imunologie MeSH
- interleukin-6 agonisté genetika imunologie MeSH
- játra účinky léků imunologie patologie MeSH
- kovové nanočástice aplikace a dávkování toxicita MeSH
- látky znečišťující vzduch farmakokinetika toxicita MeSH
- myši inbrední ICR MeSH
- myši MeSH
- NF-kappa B agonisté genetika imunologie MeSH
- olovo farmakokinetika toxicita MeSH
- plíce účinky léků imunologie patologie MeSH
- poločas MeSH
- spektrofotometrie atomová MeSH
- tkáňová distribuce MeSH
- TNF-alfa agonisté genetika imunologie MeSH
- transformující růstový faktor beta1 agonisté genetika imunologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In vitro three-dimensional (3D) lung cell models have been thoroughly investigated in recent years and provide a reliable tool to assess the hazard associated with nanomaterials (NMs) released into the air. In this study, a 3D lung co-culture model was optimized to assess the hazard potential of multiwalled carbon nanotubes (MWCNTs), which is known to provoke inflammation and fibrosis, critical adverse outcomes linked to acute and prolonged NM exposure. The lung co-cultures were exposed to MWCNTs at the air-liquid interface (ALI) using the VITROCELL® Cloud system while considering realistic occupational exposure doses. The co-culture model was composed of three human cell lines: alveolar epithelial cells (A549), fibroblasts (MRC-5), and macrophages (differentiated THP-1). The model was exposed to two types of MWCNTs (Mitsui-7 and Nanocyl) at different concentrations (2-10 μg/cm2) to assess the proinflammatory as well as the profibrotic responses after acute (24 h, one exposure) and prolonged (96 h, repeated exposures) exposure cycles. The results showed that acute or prolonged exposure to different concentrations of the tested MWCNTs did not induce cytotoxicity or apparent profibrotic response; however, suggested the onset of proinflammatory response.
- MeSH
- aerosoly MeSH
- alveolární makrofágy metabolismus patologie MeSH
- biologické modely * MeSH
- buňky A549 MeSH
- fibroblasty metabolismus patologie MeSH
- lidé MeSH
- nanotrubičky uhlíkové škodlivé účinky MeSH
- pneumocyty metabolismus patologie MeSH
- THP-1 buňky MeSH
- zánět chemicky indukované metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
AIMS: To elucidate the role of alveolar macrophages (AM) in the pathogenesis of hypoxic pulmonary hypertension (HPH), we tested the effects of sustained hypoxia on AM polarization and on the formation of superoxide by AM in vivo and in vitro. MAIN METHODS: Rat AM were obtained by bronchoalveolar lavage. 4-day exposure to hypoxia (10% O2) was carried out in vivo (rats in isobaric hypoxic chamber, controls kept in air) or in vitro (control AM in 21% O2 and 5% CO2). Superoxide production was measured by luminol-orthovanadate chemiluminescence, AM polarization was detected immunocytochemically. To ascertain the effect of substances contained in the alveolar environment, we cultivated cells also in the presence of non-cellular components of the bronchoalveolar lavage fluid (BALF) either from controls or from rats exposed to 4 days of hypoxia. KEY FINDINGS: In vivo, but not in vitro, hypoxia increased AM superoxide production. Both types of hypoxia polarized AM into M2 (pro-proliferative) type. While the presence of control BALF attenuated superoxide production in AM cultivated in normoxia, BALF from the hypoxia-exposed rats had no effect. In AM cultivated in hypoxia, superoxide production was not altered by control BALF and elevated by BALF obtained from hypoxic rats. SIGNIFICANCE: Hypoxia does not influence superoxide production by AM directly but rather by modulating their milieu and their sensitivity to external influences.
- MeSH
- alveolární makrofágy metabolismus patologie MeSH
- bronchoalveolární lavážní tekutina chemie MeSH
- hypoxie patofyziologie MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- potkani Wistar MeSH
- superoxidy metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Epidermolysis bullosa a Bartov syndróm sú pomerne presne histopatologicky dokumentované ochorenia. V príspevku autori približujú zaujímavý a doteraz neopísaný úkaz v pľúcach dieťaťa mužského pohlavia s epidermolysis bullosa junctionalis a s Bartovým syndrómom, ktoré zomrelo po 17 dňoch od narodenia a 13 dňoch od vykonania operácie pre atréziu pylora na multiorgánové zlyhanie pri základných vrodených ochoreniach. Pri histologickom vyšetrení sa v alveolách pľúc našli okrem masívnej prítomnosti penovitých makrofágov aj početné globoidné útvary pripomínajúce morfologicky aj imunohistochemicky Hassallove telieska v týmuse novorodenca. Išlo o acidofilné sférické telieska s koncentrickou skladbou, vo väzivovom tkanive s fokálnou prítomnosťou fibrínu a s ojedinelým dôkazom cytokeratínu AE1/AE3 a cytokeratínu HMW pozitívnych epitélií a s CD68 pozitívnymi histiocytovými elementmi, ktoré autori pracovne nazvali „hassalloidnými“ telieskami. Zaujímavým nálezom bola aj folikulárna kožná štruktúra v centre „hassalloidného“ telieska, ktorá svedčí o aspirácii súčasti kože počas intrauterinného života. Normálne Apgarovej skóre pri narodení dieťaťa (10/10/10 b.) a závažný histomorfologický nález pri úmrtí dieťaťa najskôr svedčia o patogenetickej formácii „hassalloidných“ teliesok v pľúcach počas 17-dňového života postihnutého dieťaťa.
Epidermolysis bullosa and Bart´s syndrome are fairly accurately documented diseases by histopathology. In the article the authors describe interesting and hitherto undescribed phenomenon in the lungs male infant with epidermolysis bullosa junctionalis and Bart‘s syndrome, who died 17 days after birth and 13 days after surgery for pyloric atresia, on multiorgan failure within basic congenital diseases. Histologically in lung alveoli was found to the massive presence of foamy macrophages and numerous globoid formations resembling morphological and immunohistochemical „Hassall´s” bodies in a thymus of the newborn. It was a acidophillic spherical bodies concentric tracks in the connective tissue with focal presence of fibrin, as a unique proof CKAE1/AE3 and CKHMW positive epithelial cells and CD68-positive histiocytic elements. An interesting finding was the follicular skin structure in the center „hassalloid´s-like” body, which suggests an aspiration components of the skin during intrauterine life. Normal Apgar score at birth of the child (10/10/10 s.) and severe histological features on the death of the child testify for the first pathogenetic formation „hassalloid´s-like” bodies in the lungs during the 17-day life of a disabled child.
- Klíčová slova
- Bartův syndrom, pěnovité makrofágy, Hassallova tělíska,
- MeSH
- alveolární makrofágy * patologie MeSH
- epidermolysis bullosa junkční * MeSH
- kožní nemoci MeSH
- lidé MeSH
- novorozenec MeSH
- pitva MeSH
- plíce patologie MeSH
- plicní alveoly * patologie MeSH
- syndrom MeSH
- thymus MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- Publikační typ
- kazuistiky MeSH
Epidermolysis bullosa predstavuje skupinu mechanobulóznych ochorení, ktoré sú najčastejšie dedične podmienené. V článku opisujeme prípad 15-dňového novorodenca ženského pohlavia s kongenitálnou epidermolysis bullosa postihujúcou približne 1/3 povrchu kože. Dieťa zomrelo v dôsledku nezvládnuteľnej sepsy s multiorgánovým zlyhaním. Predmetom nášho príspevku je popis neobvyklého pľúcneho nálezu s masívnym vyplnením alveolov penovitými makrofágmi po aspirácii súčastí plodovej vody obsahujúcej nadmerné množstvo odlúčených epitélií pokožky. Prezentovaný prípad poukazuje na výraznú diskrepanciu negatívneho klinického a závažného histopatologického nálezu.
Epidermolysis bullosa represents a group of mechanobullous diseases which are most commonly genetically determined. We describe the case of a 15-day-old female newborn with congenital epidermolysis bullosa which was inflicted on aproximately 1/3 of her skin surface, who died because of incorrigible sepsis with multiorgan failure. The main topic of our report is a description of an unusual pulmonary finding of massive alveolar filling with foamy macrophages after amnion fluid aspiration, which contained a excessive amount of desquamated epidermal cells. Introduced case shows outstanding discrepancy of negative clinical finding on one side and massive histopathological finding on the other.
- MeSH
- alveolární makrofágy patologie MeSH
- epidermolysis bullosa * diagnóza komplikace patologie MeSH
- imunohistochemie MeSH
- lidé MeSH
- multiorgánové selhání MeSH
- novorozenec MeSH
- pitva MeSH
- plíce patologie MeSH
- plicní alveoly patologie MeSH
- příčina smrti MeSH
- sepse etiologie MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
Účel prehľadu: Dôležitým kľúčom v hľadaní nových možností liečby chronickej obštrukčnej choroby pľúc (CHOCHP) je poznanie chronického zápalového procesu, ktorý postihuje dýchacie cesty pacientov s týmto ochorením. Hlavné zápalové bunky a mediátory, ktoré pôsobia v patogenéze CHOCHP, sú známe, ale málo sa vie o ich vzájomnom spolupôsobení, ktoré v konečnom dôsledku vedie ku štrukturálnym zmenám v dýchacích cestách a k postupnému obmedzeniu dychového prietoku. Nové poznatky: Nedávne štúdie priniesli nové teórie vysvetľujúce zápalové dráhy pri CHOCHP a zaoberali sa nielen vplyvom cigaretového dymu, ale aj inými faktormi, ktoré podnecujú zápal dýchacích ciest. Je dokázané, že okrem neutrofilov a makrofágov môžu hrať v patogenéze CHOCHP dôležitú úlohu aj eozinofily a pacienti s eozinofilným zápalom môžu predstavovať charakteristický fenotyp. To môže ovplyvňovať liečbu. V patogenéze CHOCHP sa objavili nové cytokíny (napr. interleukín 32). Zvýšený počet zápalových bunkových subpopulácií nemusí nutne súvisieť aj s ich zvýšenou aktivitou, čo svedčí o ich komplexnej úlohe v navodení/zachovaní zápalu dýchacích ciest pri CHOCHP. V priebehu CHOCHP sa zistila aj prítomnosť zápalu v horných dýchacích cestách. Súhrn: V patogenéze CHOCHP stále zostáva veľa nezodpovedaných otázok. Výsledky nedávno publikovaných štúdií poukazujú na nový prístup ku zápalu dýchacích ciest v CHOCHP a naznačujú nové zaujímavé smerovanie vo výskume CHOCHP.
PURPOSE OF REVIEW: Understanding the chronic inflammatory process that affects the airways of patients with chronic obstructive pulmonary disease (COPD) is an important clue in the search for new therapeutic options. The main inflammatory cells and mediators involved in COPD pathogenesis have been identified, but there is still little knowledge about their mutual interactions that result in the final outcome, that is, structural airway changes and progressive airflow limitation. RECENT FINDINGS: Recent studies created novel theories on the inflammatory pathway in COPD and focused not only on the influence of cigarette smoke but also on other factors initiating airway inflammation. There is evidence that apart from neutrophils and macrophages, eosinophils may play an important role in the pathogenesis of COPD and patients with eosinophilic inflammation may present a distinct phenotype. This may have therapeutic implications. New cytokines (e.g. interleukin 32) involved in COPD pathogenesis have been identified. The increased number of inflammatory cell subpopulations need not necessarily be associated with their increased activity, suggesting their complex role in inducing/sustaining airway inflammation in COPD. The presence of inflammation in the upper airways in the course of COPD has also been found. SUMMARY: There are many questions concerning the pathogenesis of COPD yet to be answered. Results of recently published studies show a new approach to airway inflammation in COPD and indicate new interesting directions in COPD research.
The aim of this work was to compare in vitro nitric oxide (NO) production by rat, bovine and porcine macrophages. NO production was induced by lipopolysaccharide (LPS) or by phorbol 12-myristate 13-acetate (PMA) with ionomycin or recombinant interferon gamma (rIFN-gamma) and was assessed by Griess reaction. NO synthase type II (NOS II) expression was quantified by immunocytochemistry, Western blot and real-time polymerase chain reaction (RT-PCR). There were differences in NO production by pulmonary alveolar macrophages (PAM) in all species tested. The largest amounts of NO were produced by rat PAM. Less NO was produced by bovine PAM. Moreover, PAM in rats and cows differed in their abilities to respond to various stimulators. Neither porcine PAM nor Kupffer cells produced NO. Stimulation of porcine PAM with alternative concentrations of LPS did not lead to inducing NO production. Stimulation of porcine PAM with rIFN-gamma together with LPS led to a significant increase in the expression of NOS II mRNA, albeit without detectable NO production or NOS II expression on the protein level.
- MeSH
- alveolární makrofágy metabolismus patologie MeSH
- biotest MeSH
- ethylendiaminy MeSH
- financování organizované MeSH
- imunohistochemie MeSH
- interferon gama toxicita MeSH
- ionomycin toxicita MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- lipopolysacharidy toxicita MeSH
- messenger RNA metabolismus MeSH
- oxid dusnatý analýza metabolismus MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- prasata MeSH
- regulace genové exprese enzymů MeSH
- skot MeSH
- sulfanilamidy MeSH
- synthasa oxidu dusnatého, typ II genetika metabolismus MeSH
- tetradekanoylforbolacetát toxicita MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- skot MeSH
- zvířata MeSH
- MeSH
- alveolární makrofágy patologie MeSH
- fibroblasty patologie MeSH
- plicní alveoly patofyziologie patologie MeSH
- silikóza etiologie patologie MeSH
- Publikační typ
- přehledy MeSH
x
x
- MeSH
- alveolární makrofágy imunologie patologie MeSH
- cytokiny farmakologie izolace a purifikace škodlivé účinky MeSH
- intersticiální plicní nemoci imunologie patofyziologie MeSH
- lidé MeSH
- nemoci z povolání MeSH
- pneumokonióza epidemiologie imunologie MeSH
- prach * imunologie MeSH
- pracovní expozice MeSH
- reaktivní formy kyslíku škodlivé účinky MeSH
- Check Tag
- lidé MeSH
