Glutathione peroxidase 3 localizes to the epithelial lining fluid and the extracellular matrix in interstitial lung disease

Insulin-like growth factor-1 (IGF-1) is involved in regulating the TH-l/TH-2 balance, favoring the development of the TH-2 compartment which enhances fibrosis, one of the main characteristics of Chronic Lung Disease (CLD) in premature newborns. Limited data is available concerning a possible association between early epithelial lining fluid (ELF) concentrations of IGF-1 (total and free forms), IGF-binding protein-3 (IGFBP-3), b2-microglobulin (B2M) and subsequent development of CLD in preterm neonates. If neutropenic, preterm neonates are frequently treated with recombinant human Granulocyte Colony Stimulating Factor (rhG-CSF). The objective of the study was to correlate ELF concentrations of IGF-1 and B2M during the first week of life both in non-neutropenic and in rhG-CSF-treated neutropenic preterm neonates, with subsequent development in CLD. Thirty preterm neonates with Respiratory Distress Syndrome (6 with neutropenia) were studied. Eleven out of 24 non-neutropenic preterm infants (46%) and all of the six neutropenic subjects (100%) developed CLD. With the exception of first day values, there was a clear similarity in the behaviors of assayed molecules between non-neutropenic and neutropenic patients developing CLD. Non-neutropenic patients without CLD showed significantly lower values of free IGF-1 and B2M both on days 1 and 3. Total IGF-I and cell counts were different only on the 3rd day. Conclusions: 1) the mechanisms leading to CLD might be mediated by high levels of IGF-family molecules soon after birth 2) B2M could be a marker of increased bronchoalveolar lavage fluid cellularity with potential inflammatory properties 3) G-CSF treatment induces an increased synthesis of IGF-1 molecules by cells recruited in the lung, with possible enhancement of the fibrogenic mechanisms.

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Extracellular glutathione peroxidase in human lung epithelial lining fluid and in lung cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1996.270.2.l173 ◽

1996 ◽

Vol 270 (2) ◽

pp. L173-L182 ◽

Cited By ~ 22

Author(s):

N. Avissar ◽

J. N. Finkelstein ◽

S. Horowitz ◽

J. C. Willey ◽

E. Coy ◽

...

Keyword(s):

Epithelial Cells ◽

Glutathione Peroxidase ◽

Bronchial Epithelial Cell ◽

Interstitial Cells ◽

Lung Cells ◽

Epithelial Lining ◽

Bronchial Epithelial ◽

Epithelial Lining Fluid ◽

Epithelial Cell Lines ◽

Gpx Activity

The epithelial cells of the lower respiratory tract are exposed to high levels of inhaled oxygen and other oxidants. We hypothesized that lung cells would secrete the antioxidant enzyme, extracellular glutathione peroxidase (eGPx), into epithelial lining fluid (ELF). To investigate this hypothesis, we used specific immunoprecipitations of GPx enzymes from ELF, specific immunoprecipitations of 75Se metabolically labeled proteins from lung cells in culture, and in situ hybridization, Northern blot, and reverse transcription-polymerase chain reaction (RT-PCR) analyses. Fifty-seven percent of ELF GPx activity was due to eGPx and 40% was due to cellular GPx (cGPx). Primary bronchial epithelial cells (BEC), primary alveolar macrophages (AM), and two human bronchial epithelial cell lines, BEP2D and A549, synthesized both eGPx and cGPx and secreted eGPx into the medium. Freshly isolated human AM and BEC expressed eGPx mRNA, while freshly isolated rabbit type 2 pneumocytes did not. In lung tissue, eGPx mRNA was found mainly in interstitial cells of tissue surrounding airways. It is concluded that more than half of GPx activity in BAL is due to eGPx, and that BEC, AM, and interstitial cells are potential sources of pulmonary eGPx.

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Epithelial lining fluid solute concentrations in chronic obstructive lung disease patients and normal subjects

Journal of Applied Physiology ◽

10.1152/japplphysiol.00362.2005 ◽

2005 ◽

Vol 99 (4) ◽

pp. 1286-1292 ◽

Cited By ~ 49

Author(s):

Richard M. Effros ◽

Barry Peterson ◽

Richard Casaburi ◽

Jennifer Su ◽

Marshall Dunning ◽

...

Keyword(s):

Water Vapor ◽

Lung Disease ◽

Obstructive Lung Disease ◽

Plasma Concentrations ◽

Chronic Obstructive Lung Disease ◽

Chronic Obstructive ◽

Exhaled Breath ◽

Epithelial Lining ◽

Epithelial Lining Fluid ◽

Respiratory Droplets

The exhaled breath condensate (EBC) method represents a new, noninvasive way to detect inflammatory and metabolic markers in the fluid that covers the airways [epithelial lining fluid (ELF)]. However, respiratory droplets represent only a very small and variable fraction of the EBC, most (∼99.99%) of which is water vapor. Our objective was to show that ELF concentrations could be calculated from EBC values by using any of three dilutional indicators (urea, total cations, and conductivity) in nine normal and nine chronic obstructive lung disease (COPD) subjects. EBC concentrations of Na+, K+, Ca2+, Mg2+, total cations, urea, and conductivity varied over a 10-fold range among individuals, but concentrations of these constituents (except Ca2+) remained well correlated ( r2 = 0.44–0.83, P < 0.001). Dilution (D) of respiratory droplets in water vapor was calculated by dividing plasma concentrations of the dilutional indicators by EBC concentrations. Estimates of D were not significantly different among these indicators, and urea D averaged 10,800 ± 2,100 (SE) in normal and 12,600 ± 3,300 in COPD subjects. Although calculated Na+ concentrations in the ELF were less than one-half those in plasma, and concentrations of K+, Ca2+, and Mg2+ exceeded those in plasma, total cation concentrations in ELF were not significantly different from those in plasma, indicating that ELF is isotonic in both normal and COPD subjects. EBC amylase concentrations (measured with an ultrasensitive procedure) indicated that saliva represented <10% of the respiratory (ELF) droplets in all but three samples. Dilutional and salivary markers are essential for interpretation of EBC studies.

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