scholarly journals The role of inducible nitric oxide synthase for interstitial remodeling of alveolar septa in surfactant protein D-deficient mice

2015 ◽  
Vol 309 (9) ◽  
pp. L959-L969 ◽  
Author(s):  
Lars Knudsen ◽  
Elena N. Atochina-Vasserman ◽  
Christopher B. Massa ◽  
Bastian Birkelbach ◽  
Chang-Jiang Guo ◽  
...  
Keyword(s):  
Surface Area ◽  
Wall Thickness ◽  
Alveolar Epithelium ◽  
Surfactant Protein ◽  
Lung Mechanics ◽  
Surfactant Protein D ◽  
Wall Thickening ◽  
Interstitial Tissue ◽  
Septal Wall ◽  
Septal Wall Thickness

Surfactant protein D (SP-D) modulates the lung's immune system. Its absence leads to NOS2-independent alveolar lipoproteinosis and NOS2-dependent chronic inflammation, which is critical for early emphysematous remodeling. With aging, SP-D knockout mice develop an additional interstitial fibrotic component. We hypothesize that this age-related interstitial septal wall remodeling is mediated by NOS2. Using invasive pulmonary function testing such as the forced oscillation technique and quasistatic pressure-volume perturbation and design-based stereology, we compared 29-wk-old SP-D knockout (Sftpd−/−) mice, SP-D/NOS2 double-knockout (DiNOS) mice, and wild-type mice (WT). Structural changes, including alveolar epithelial surface area, distribution of septal wall thickness, and volumes of septal wall components (alveolar epithelium, interstitial tissue, and endothelium) were quantified. Twenty-nine-week-old Sftpd−/− mice had preserved lung mechanics at the organ level, whereas elastance was increased in DiNOS. Airspace enlargement and loss of surface area of alveolar epithelium coexist with increased septal wall thickness in Sftpd−/− mice. These changes were reduced in DiNOS, and compared with Sftpd−/− mice a decrease in volumes of interstitial tissue and alveolar epithelium was found. To understand the effects of lung pathology on measured lung mechanics, structural data were used to inform a computational model, simulating lung mechanics as a function of airspace derecruitment, septal wall destruction (loss of surface area), and septal wall thickening. In conclusion, NOS2 mediates remodeling of septal walls, resulting in deposition of interstitial tissue in Sftpd−/−. Forward modeling linking structure and lung mechanics describes the complex mechanical properties by parenchymatous destruction (emphysema), interstitial remodeling (septal wall thickening), and altered recruitability of acinar airspaces.

Pulmonary mechanical and immunologic dysfunction in a murine model of AIDS

1997 ◽  
Vol 272 (4) ◽  
pp. L699-L706 ◽  
Author(s):  
C. L. Hartsfield ◽  
D. Lipke ◽  
Y. L. Lai ◽  
D. A. Cohen ◽  
M. N. Gillespie
Keyword(s):  
Gas Exchange ◽  
Wall Thickness ◽  
Murine Model ◽  
Acquired Immunodeficiency Syndrome ◽  
Wall Thickening ◽  
Diffusion Capacity ◽  
Septal Wall ◽  
Septal Wall Thickness ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome

Human immunodeficiency virus-infected patients occasionally exhibit alveolar septal wall thickening and decreases in gas diffusion capacity, but the mechanism underlying these abnormalities is unknown. The present study evaluated septal wall thickness and gas exchange properties in a murine model of the acquired immunodeficiency syndrome and determined whether there were alterations in lung lymphocyte deposition and activation that could contribute to changes in respiratory structure and function. Although alveolar septal wall thickness did not differ from control at 1, 2, and 4 wk postimmunosuppressive virus infection, at 8 wk after infection, septal wall thickness was substantially increased. Immunohistochemical evaluation at this time revealed marked increases in the septal wall deposition of fibronectin and collagen type IV. Pulmonary function tests on anesthetized mice with virus-induced septal wall thickening demonstrated that, although total lung capacity, compliance, and functional residual capacity were unaltered, diffusion capacity for carbon monoxide was significantly impaired. A diffuse nonspecific interstitial pneumonitis was present in lungs of immunodeficient mice, and flow cytometry indicated that both lymphocytes and macrophages were activated. Reverse transcriptase-polymerase chain reaction analysis of lung lymphocytes demonstrated enhanced mRNA expression for several cytokines known to affect lung structure. These results show that impaired gas exchange occurs in a murine model of acquired immunodeficiency syndrome and suggest that such alterations may be mediated by elaboration of cytokines from activated lung lymphocytes and macrophages.

scholarly journals Expression of Surfactant protein D (SP-D) distinguishes severe pandemic influenza A(H1N1) from COVID-19

2021 ◽  
Author(s):  
José Alberto Choreño-Parra ◽  
Luis Armando Jiménez-Álvarez ◽  
Gustavo Ramírez-Martínez ◽  
Alfredo Cruz-Lagunas ◽  
Mahima Thapa ◽  
...  
Keyword(s):  
Pandemic Influenza ◽  
Influenza A ◽  
Alveolar Epithelium ◽  
Surfactant Protein ◽  
High Serum ◽  
Surfactant Protein D ◽  
Diagnostic Challenge ◽  
Moderate Disease ◽  
Influenza A H1n1 ◽  
Novel Biomarkers

Abstract The differentiation of influenza and COVID-19 could constitute a diagnostic challenge during the ongoing winter due to their clinical similitude. Thus, novel biomarkers that enable distinguishing both diseases are required. Here, we evaluated whether the surfactant protein D (SP-D), a collectin produced at the alveolar epithelium with known immune properties, was useful to differentiate pandemic influenza A(H1N1) from COVID-19 in critically ill patients. Our results revealed high serum SP-D levels in severe pandemic influenza but not COVID-19 patients. This finding was validated in a separate cohort of mechanically ventilated COVID-19 patients who also showed low plasma SP-D levels. However, plasma SP-D levels did not distinguish seasonal influenza from COVID-19 in mild-to-moderate disease. Finally, we found that high serum SP-D levels were associated with mortality and renal failure among severe pandemic influenza cases. Thus, our studies have identified SP-D as a unique biomarker expressed during severe pandemic influenza but not COVID-19.

scholarly journals C/EBPα is required for pulmonary cytoprotection during hyperoxia

2009 ◽  
Vol 297 (2) ◽  
pp. L286-L298 ◽  
Author(s):  
Yan Xu ◽  
Chika Saegusa ◽  
Angelica Schehr ◽  
Shawn Grant ◽  
Jeffrey A. Whitsett ◽  
...  
Keyword(s):  
Protein Biosynthesis ◽  
Critical Role ◽  
Alveolar Epithelium ◽  
Surfactant Protein ◽  
Lung Mechanics ◽  
Type Ii Cells ◽  
Type Ii ◽  
Clara Cells ◽  
Lung Maturation ◽  
Surfactant Lipid

A number of transcriptional pathways regulating fetal lung development are active during repair of the injured lung. We hypothesized that C/EBPα, a transcription factor critical for lung maturation, plays a role in protection of the alveolar epithelium following hyperoxic injury of the mature lung. Transgenic CebpαΔ/Δmice, in which Cebpα was conditionally deleted from Clara cells and type II cells after birth, were developed. While no pulmonary abnormalities were observed in the CebpαΔ/Δmice (7–8 wk old) under normal conditions, the mice were highly susceptible to hyperoxia. CebpαΔ/Δmice died within 4 days of exposure to 95% oxygen in association with severe lung inflammation, altered maturation of surfactant protein B and C, decreased surfactant lipid secretion, and abnormal lung mechanics at a time when all control mice survived. mRNA microarray analysis of isolated type II cells at 0, 2, and 24 h of hyperoxia demonstrated the reduced expression of number of genes regulating surfactant lipid and protein homeostasis, including Srebf, Scap, Lpcat1, Abca3, Sftpb, and Napsa. Genes influencing cell signaling or immune responses were induced in the lungs of CebpαΔ/Δmice. C/EBPα was required for the regulation of genes associated with surfactant lipid homeostasis, surfactant protein biosynthesis, processing and transport, defense response to stress, and cell redox homeostasis during exposure to hyperoxia. While C/EBPα did not play a critical role in postnatal pulmonary function under normal conditions, C/EBPα mediated protection of the lung during acute lung injury induced by hyperoxia.

scholarly journals Investigating biases in the measurement of apparent alveolar septal wall thickness with hyperpolarized 129Xe MRI

2020 ◽  
Vol 84 (6) ◽  
pp. 3027-3039
Author(s):  
Kai Ruppert ◽  
Faraz Amzajerdian ◽  
Yi Xin ◽  
Hooman Hamedani ◽  
Luis Loza ◽  
...  
Keyword(s):  
Wall Thickness ◽  
Septal Wall ◽  
Hyperpolarized 129Xe ◽  
Septal Wall Thickness

scholarly journals Maladaptive Changes Associated With Cardiac Aging Are Sex-Specific and Graded by Frailty and Inflammation in C57BL/6 Mice

2020 ◽  
Author(s):  
Alice E Kane ◽  
Elise S Bisset ◽  
Stefan Heinze-Milne ◽  
Kaitlyn M Keller ◽  
Scott A Grandy ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Wall Thickness ◽  
Structure And Function ◽  
Cardiac Structure ◽  
Septal Wall ◽  
Serum Cytokines ◽  
Lv Mass ◽  
Septal Wall Thickness ◽  
Cardiac Structure And Function ◽  
And Function

Abstract We investigated whether late-life changes in cardiac structure and function were related to high levels of frailty and inflammation in male and female mice. Frailty (frailty index), ventricular structure/function (echocardiography), and serum cytokines (multiplex immunoassay) were measured in 16- and 23-month-old mice. Left ventricular (LV) mass and septal wall thickness increased with age in both sexes. Ejection fraction increased with age in males (60.4 ± 1.4 vs 68.9 ± 1.8%; p < .05) but not females (58.8 ± 2.5 vs 62.6 ± 2.4%). E/A ratios declined with age in males (1.6 ± 0.1 vs 1.3 ± 0.1; p < .05) but not females (1.4 ± 0.1 vs 1.3 ± 0.1) and this was accompanied by increased ventricular collagen levels in males. These changes in ejection fraction (r = 0.52; p = .01), septal wall thickness (r = 0.59; p = .002), E/A ratios (r = −0.49; p = .04), and fibrosis (r = 0.82; p = .002) were closely graded by frailty scores in males. Only septal wall thickness and LV mass increased with frailty in females. Serum cytokines changed modestly with age in both sexes. Nonetheless, in males, E/A ratios, LV mass, LV posterior wall thickness, and septal wall thickness increased as serum cytokines increased (eg, IL-6, IL-3, IL-1α, IL-1β, tumor necrosis factor-α, eotaxin, and macrophage inflammatory protein-1α), while ejection fraction declined with increasing IL-3 and granulocyte-macrophage colony stimulating factor. Cardiac outcomes were not correlated with inflammatory cytokines in females. Thus, changes in cardiac structure and function in late life are closely graded by both frailty and markers of inflammation, but this occurs primarily in males. This suggests poor overall health and inflammation drive maladaptive changes in older male hearts, while older females may be resistant to these adverse effects of frailty.

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