A Morphological Study of Acute Respiratory Tract Lesions in a Lipopolysaccharide Instilled Rat Model.

Ooi, Hidemi; Arakawa, Masaaki; Ozawa, Hiroki

doi:10.1679/aohc.57.87

Cited by 13 publications

(14 citation statements)

References 20 publications

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“…It is puzzling that either nonciliated or basal cells are progenitors of ciliated cells. The studies by some authors confirmed the important role played by nonciliated cells are progenitor cells in the regenerating tracheobronchial epithelium [19,20,37]. A hypothetical model was also proposed for the formation of pseudostratified mucociliary epithelium in the hamster tracheae.…”

Section: Discussionmentioning

confidence: 80%

DNA Synthesis in the Tracheae of Aging Mice by Light and Electron Microscopic Radioautography.

Sun

Gao

Jin

et al. 1997

Acta Histochem. Cytochem

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Section: Discussionmentioning

confidence: 80%

DNA Synthesis in the Tracheae of Aging Mice by Light and Electron Microscopic Radioautography.

Sun

Gao

Jin

et al. 1997

Acta Histochem. Cytochem

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“…5). Both IT LPS (32,53) and VILI (45) have been shown to cause airway injury with increased airway edema associated with increased airway epithelial permeability and apoptosis. Thus it is possible that PDE2A knockdown in this cellular compartment could significantly contribute to the beneficial effects we observed in the overall LPS/VILI insult in mice infected with Ad.PDE2A-shRNA.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of lung phosphodiesterase 2A attenuates alveolar inflammation and protein leak in a two-hit mouse model of acute lung injury

Rentsendorj

Damarla

Aggarwal

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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is stimulated by cGMP to hydrolyze cAMP, a potent endothelial barrier-protective molecule. We previously found that lung PDE2A contributed to a mouse model of ventilator-induced lung injury (VILI). The purpose of the present study was to determine the contribution of PDE2A in a two-hit mouse model of 1-day intratracheal (IT) LPS followed by 4 h of 20 ml/kg tidal volume ventilation. Compared with IT water controls, LPS alone (3.75 g/g body wt) increased lung PDE2A mRNA and protein expression by 6 h with a persistent increase in protein through day 4 before decreasing to control levels on days 6 and 10. Similar to the PDE2A time course, the peak in bronchoalveolar lavage (BAL) neutrophils, lactate dehydrogenase (LDH), and protein concentration also occurred on day 4 post-LPS. IT LPS (1 day) and VILI caused a threefold increase in lung PDE2A and inducible nitric oxide synthase (iNOS) and a 24-fold increase in BAL neutrophilia. Compared with a control adenovirus, PDE2A knockdown with an adenovirus expressing a short hairpin RNA administered IT 3 days before LPS/VILI effectively decreased lung PDE2A expression and significantly attenuated BAL neutrophilia, LDH, protein, and chemokine levels. PDE2A knockdown also reduced lung iNOS expression by 53%, increased lung cAMP by nearly twofold, and improved survival from 47 to 100%. We conclude that in a mouse model of LPS/VILI, a synergistic increase in lung PDE2A expression increased lung iNOS and alveolar inflammation and contributed significantly to the ensuing acute lung injury.lipopolysaccharide; ventilator-induced; cyclic guanosine monophosphate; inducible nitric oxide synthase; cAMP SEVERE PNEUMONIA IS A FREQUENT cause of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) (49). ARDS is characterized by neutrophil infiltration, the generation of toxic cytokines and reactive oxygen species (ROS), increased NO production and the loss of endothelial and epithelial barrier function (4). These features can be reproduced in animal models by the installation of intratracheal (IT) LPS (10, 24, 31), a key component of the gram-negative bacterial cell wall. LPS, through Toll-like receptor-4 signaling, was shown to cause increased NO from phosphorylated endothelial (eNOS) (11) and inducible nitric oxide synthase (iNOS) (24, 31) in alveolar macrophages, neutrophils, epithelium, and endothelium. NO from both eNOS and iNOS was found to play a major pathogenic role in ALI from LPS (24, 31, 42) and in ventilator-induced lung injury (VILI) (33, 39). These injurious effects of endogenous NO have been attributed to a reaction with superoxide to generate peroxynitrite (31, 33). In both LPS-induced ALI (47) and VILI (39), however, NO also activates soluble guanylyl cyclase (sGC), increasing production of cGMP in multiple cell types including endothelium (39), epithelium (9, 17), and macrophages (3).The effects of cGMP signaling in ALI are complex, depending on cell type, intracellular compartmentalization, and the downstream cGMP targets (39). These targets include...

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“…The Clara cell displays a great structural plasticity when confronted to a wide range of stimuli from hormones, toxic injuries or mediators, which inXuence its secretory activity. Many inhaled pollutants such as ozone provoke the release of the secretory granules (Evans et al 1978), while a variety of microorganisms or their by-products, including bacterial endotoxins, have been shown to induce typical morphological alterations associated to an enhanced secretory activity, such as smooth and rough endoplasmic reticulum proliferation, accumulation of free ribosomes and protrusion of the apical cytoplasm, indicating apocrine secretion (Ooi et al 1994). Also, the release of the main secretory product of Clara cells, the CC16 protein, increased signiWcantly in animals exposed to organophosphorated insecticides (Elia et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Budesonide effects on Clara cell under normal and allergic inflammatory condition

Roth

Quintar

Echevarría

et al. 2006

Histochem Cell Biol

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Clara cells are nonciliated secretory cells implicated in lung homeostasis by the synthesis of immunomodulatory and host defense products, being one of the most important the CC16 protein. In this study, we compared the effects of budesonide (BUD), an inhaled corticoid, on Clara cell biology and its ability to reverse morphofunctional changes induced in an allergic airway hyper-responsiveness mouse model. In normal mice, exposure to BUD induced morphological changes compatible with a state of maximal differentiation on CC16 positive cells which developed a prominent cupola filled up with numerous mitochondria rich in CYP2E1, a member of the cytochrome P450 family. Consequently, CYP2E1 expression raised significantly. Exposure to OVA provoked hypertrophy of Clara cells and an increment in their number per millimeter of basal membrane. These cells acquired a mucous cell phenotype characterized by a notorious expansion of the secretory granular content. Synthesis of CC16 was greatly up-regulated concurrent to the finding of MUC5AC expression and the increment of epidermal growth factor receptor (EGFR). Mitochondrial content decreased significantly with a consequent reduction in CYP2E1 expression. After BUD treatment of OVA-challenged animals, the majority of Clara cells regained their normal morphology and functional characteristics; CYP2E1 levels raised when compared to the OVA exposed group. The BUD potential to differentiate Clara cells appeared to be important for the regression of the profound changes generated by the allergic injury. These results demonstrated the wide range of stimuli that can modify different aspects of Clara cell biology, and highlighted the effects of budesonide as a modulator of P450 enzymes, which probably contributes to a complementary antiinflamatory activity.

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A Morphological Study of Acute Respiratory Tract Lesions in a Lipopolysaccharide Instilled Rat Model.

Cited by 13 publications

References 20 publications

DNA Synthesis in the Tracheae of Aging Mice by Light and Electron Microscopic Radioautography.

DNA Synthesis in the Tracheae of Aging Mice by Light and Electron Microscopic Radioautography.

Knockdown of lung phosphodiesterase 2A attenuates alveolar inflammation and protein leak in a two-hit mouse model of acute lung injury

Budesonide effects on Clara cell under normal and allergic inflammatory condition

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