Sex differences in the development of airway epithelial tolerance to naphthalene

Sutherland, Katherine; Edwards, Patricia C.; Combs, T. J.; Winkle, Laura S. Van

doi:10.1152/ajplung.00089.2011

Cited by 21 publications

(20 citation statements)

References 21 publications

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“…A similar finding of coalescing ciliated cells was reported in female mice receiving multiple doses of naphthalene (16). However, these experiments used male mice and a single dose of naphthalene.…”

Section: Discussionsupporting

confidence: 75%

“…Lungs were harvested on Days 7 and 14 after injury, and fixed at a pressure of 30 cm H 2 O with Karnovsky's fixative for scanning electron microscopy images, and with 10% formalin for histology. Airways were microdissected, and scanning electron microscopy was performed as previously described (16). Animal procedures were approved by the Institutional Animal Care and Use Committee at the University of Washington.…”

Section: Naphthalene Injurymentioning

confidence: 99%

See 1 more Smart Citation

Matrix Metalloproteinase–7 Coordinates Airway Epithelial Injury Response and Differentiation of Ciliated Cells

Gharib

Altemeier

Winkle

et al. 2013

Am J Respir Cell Mol Biol

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Matrix metalloproteinase-7 (MMP7) expression is quickly upregulated after injury, and functions to regulate wound repair and various mucosal immune processes. We evaluated the global transcriptional response of airway epithelial cells from wild-type and Mmp7-null mice cultured at an air-liquid interface. The analysis of differentially expressed genes between genotypes after injury revealed an enrichment of functional categories associated with inflammation, cilia, and differentiation. Because these analyses suggested that MMP7 regulated ciliated cell formation, we evaluated the recovery of the airway epithelium in wild-type and Mmp7-null mice in vivo after naphthalene injury, which revealed augmented ciliated cell formation in the absence of MMP7. Moreover, in vitro studies evaluating cell differentiation in air-liquid interface cultures also showed faster ciliated cell production under Mmp7-null conditions compared with wild-type conditions. These studies identified a new role for MMP7 in attenuating ciliated cell differentiation during wound repair.Keywords: MMP7; matrilysin; microarray; wound repair Like all epithelial surfaces, the lung epithelium has evolved to respond to the constant pressures exerted by the external environment, and is distinguished by an innate wound repair program initiated upon injury. Without such an efficient response, the body is left exposed to potential pathogenic invasion. More importantly, ineffective wound closure can lead to long-term adverse consequences such as chronic inflammatory states, fibrosis, and malignant transformations (1). Although the response to injury is essentially immediate, large wounds require time to repair. Therefore, injury is often accompanied by an inflammatory response that recruits leukocytes, which serve to scan for pathogens (2). Eventually, as wound healing nears completion, the associated inflammation resolves, returning the epithelium to a differentiated, homeostatic state.Matrix metalloproteinases (MMPs) comprise a family of 25 or more zinc-dependent proteases that cleave the extracellular matrix and cell-surface proteins to regulate wound healing and a variety of immune responses (3). In particular, MMP7 (matrilysin) plays a prominent role in the injury response of all mucosal epithelia. Expressed at low concentrations in the resting lung epithelium, MMP7 production is quickly induced in cells bordering the site of injury, stimulating cell migration and coordinating the inflammatory response (4-8).MMP7 is spatiotemporally regulated after injury by mechanisms that have yet to be fully elucidated (9). On one level, its expression is restricted to areas of injury (5, 7, 10). MMP7 is also secreted as a zymogen that must be activated apparently by an allosteric-mediated autolytic process (3, 9, 11). The complexity of this regulation is further magnified by the temporal selectivity with which MMP7 cleaves its substrates. For example, syndecan-1 is shed early after injury to facilitate cell migration and neutrophil recruitment into the lungs (4, 6), ...

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Section: Discussionsupporting

confidence: 75%

Section: Naphthalene Injurymentioning

confidence: 99%

Matrix Metalloproteinase–7 Coordinates Airway Epithelial Injury Response and Differentiation of Ciliated Cells

Gharib

Altemeier

Winkle

et al. 2013

Am J Respir Cell Mol Biol

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“…Chemicals that can be metabolized and impact the respiratory tract differentially by sex and age include products of combustion, such as naphthalene (32,33), smoke (34), vehicle exhaust-related air pollution (35), and the ubiquitous component of plastics, bisphenol A (BPA) (36). Early-life exposure to BPA is linked to both allergic sensitization and decrements in lung function, including wheeze, in children (30,37,38) and alterations in fetal lung maturation in experimental animals (39).…”

Section: Importance Of Diagnosismentioning

confidence: 99%

Women and Lung Disease. Sex Differences and Global Health Disparities

Pinkerton

Harbaugh

Han

et al. 2015

Am J Respir Crit Care Med

125

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There is growing evidence that a number of pulmonary diseases affect women differently and with a greater degree of severity than men. The causes for such sex disparity is the focus of this Blue Conference Perspective review, which explores basic cellular and molecular mechanisms, life stages, and clinical outcomes based on environmental, sociocultural, occupational, and infectious scenarios, as well as medical health beliefs. Owing to the breadth of issues related to women and lung disease, we present examples of both basic and clinical concepts that may be the cause for pulmonary disease disparity in women. These examples include those diseases that predominantly affect women, as well as the rising incidence among women for diseases traditionally occurring in men, such as chronic obstructive pulmonary disease. Sociocultural implications of pulmonary disease attributable to biomass burning and infectious diseases among women in low-to middle-income countries are reviewed, as are disparities in respiratory health among sexual minority women in high-income countries. The implications of the use of complementary and alternative medicine by women to influence respiratory disease are examined, and future directions for research on women and respiratory health are provided.

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“…Whole mount tissues for in situ localization of Gd 2 O 3 :Eu 3+ NPs were prepared from the right middle lobe. The lobe was dissected to expose the airways from the interlobar bronchus to terminal bronchioles and surrounding parenchyma region, 52 and imaged using a Leica TCS LSI microscope in fluorescent mode using the metal halide light source, a 340–380 nm band-pass excitation filter, 425 nm emission filter and a 40× water dipping objective.…”

Section: Methodsmentioning

confidence: 99%

Novel multi-functional europium-doped gadolinium oxide nanoparticle aerosols facilitate the study of deposition in the developing rat lung

et al. 2016

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Ambient ultrafine particulate matter (UPM), less than 100 nm in size, has been linked to the development and exacerbation of pulmonary diseases. Age differences in susceptibility to UPM may be due to a difference in delivered dose as well as age-dependent differences in lung biology and clearance. In this study, we developed and characterized aerosol exposures to novel metal oxide nanoparticles containing lanthanides to study particle deposition in the developing postnatal rat lung. Neonatal, juvenile and adult rats (1, 3 and 12 weeks old) were nose only exposed to 380 μg/m3 of ~30 nm europium doped gadolinium oxide nanoparticles (Gd2O3:Eu3+) for 1 h. The deposited dose in the nose, extrapulmonary airways and lungs was determined using inductively-coupled plasma mass spectroscopy. The dose of deposited particles was significantly greater in the juvenile rats at 2.22 ng/g body weight compared to 1.47 ng/g and 0.097 ng/g for the adult and neonate rats, respectively. Toxicity was investigated in bronchoalveolar lavage fluid (BALF) by quantifying recovered cell types, and measuring lactate dehydrogenase activity and total protein. The toxicity data suggests that the lanthanide particles were not acutely toxic or inflammatory with no increase in neutrophils or lactate dehydrogenase activity at any age. Juvenile and adult rats had the same mass of deposited NPs per gram of lung tissue, while neonatal rats had significantly less NPs deposited per gram of lung tissue. The current study demonstrates the utility of novel lanthanide-based nanoparticles to study inhaled particle deposition in vivo and has important implications for nanoparticles delivery to the developing lung either as therapies or as a portion of particulate matter air pollution.

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Sex differences in the development of airway epithelial tolerance to naphthalene

Abstract: Sutherland KM, Edwards PC, Combs TJ, Van Winkle LS. Sex differences in the development of airway epithelial tolerance to naphthalene.

Cited by 21 publications

References 21 publications

Matrix Metalloproteinase–7 Coordinates Airway Epithelial Injury Response and Differentiation of Ciliated Cells

Matrix Metalloproteinase–7 Coordinates Airway Epithelial Injury Response and Differentiation of Ciliated Cells

Women and Lung Disease. Sex Differences and Global Health Disparities

Novel multi-functional europium-doped gadolinium oxide nanoparticle aerosols facilitate the study of deposition in the developing rat lung

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