SARS-CoV-2 (COVID-19) Adhesion Site Protein Upregulation in Small Airways, Type 2 Pneumocytes, and Alveolar Macrophages of Smokers and COPD – Possible Implications for Interstitial Fibrosis

Type 2 diabetes mellitus (DM) adversely affects the outcomes in patients with myocardial infarction (MI), which is associated with the development of left ventricular (LV) remodeling and failure. NAD(P)H oxidase-derived superoxide (O 2 − ) production is increased in DM. However, its pathophysiological significance in advanced post-MI LV failure associated with DM remains unestablished. We thus determined whether an inhibitor of NAD(P)H oxidase activation, apocynin, could attenuate the exacerbated LV remodeling and heart failure after MI in high-fat diet (HFD)-induced obese mice with DM. Male C57BL/6J mice were fed on either HFD or normal diet (ND) for 8 weeks. At 4 weeks of feeding, MI was created in all mice by ligating left coronary artery. MI mice were treated with either apocynin (10 mmol/l in drinking water; n = 10 for ND and n = 11 for HFD) or vehicle (n = 15 for ND and n = 13 for HFD). HFD significantly increased body weight (BW), adipose tissue mass, fasting plasma glucose and insulin levels compared to ND after 4 and 8 weeks. HFD + MI had significantly greater LV end-diastolic diameter (LVEDD; 5.7 ± 0.1 vs. 5.3 ± 0.2 mm) by echocardiography, end-diastolic pressure (EDP; 12 ± 2 vs. 8 ± 1 mmHg) and lung weight/tibial length (10.1 ± 0.3 vs. 8.7 ± 0.7 mg/mm) than ND + MI, which was accompanied by an increased interstitial fibrosis of non-infarcted LV. Treatment of HFD + MI with apocynin significantly decreased LVEDD (5.4 ± 0.1 mm), LVEDP (9.7 ± 0.8 mmHg), lung weight/tibial length (9.0 ± 0.3 mg/mm), and concomitantly interstitial fibrosis of non-infarcted LV to ND + MI level without affecting BW, glucose metabolism, infarct size and aortic pressure. On the other hand, treatment of ND + MI with apocynin did not affect LV remodeling and failure. NAD(P)H oxidase activity, O 2 − production measured by lucigenin chemiluminescence, and thiobarbituric acid-reactive substances were increased in non-infarcted LV tissues from HFD + MI, all of which were also attenuated by apocynin to ND + MI level. Type 2 DM was associated with the exacerbation of LV remodeling and failure after MI via increasing NAD(P)H oxidase derived O 2 − production, which may be a novel important therapeutic target in advanced heart failure with DM.

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Lung Pathology in Premature Infants with Ureaplasma urealyticum Infection

Pediatric and Developmental Pathology ◽

10.1007/s10024-001-0134-y ◽

2002 ◽

Vol 5 (2) ◽

pp. 141-150 ◽

Cited By ~ 51

Author(s):

Rose M. Viscardi ◽

Winston M. Manimtim ◽

Chen-Chih J. Sun ◽

Lynn Duffy ◽

Gail H. Cassell

Keyword(s):

Alveolar Macrophages ◽

Very Low Birth Weight ◽

Ureaplasma Urealyticum ◽

Interstitial Fibrosis ◽

Tracheal Aspirate ◽

Lymphocytic Infiltration ◽

Lung Pathology ◽

Low Birth Weight Infants ◽

Cell Counts ◽

Tnf Α

Respiratory tract colonization with Ureaplasma urealyticum in preterm infants has been associated with a higher incidence of pneumonia, severe respiratory failure, bronchopulmonary dysplasia (BPD), and death. In this report, we characterize the lung pathology and expression of tumor necrosis factor-α (TNF-α) associated with U. urealyticum pneumonia in very low–birth weight infants (VLBW; ≤1500 g). Lung pathology of archived autopsy specimens was retrospectively reviewed in three groups of VLBW infants: 5 gestational controls who died from nonpulmonary causes, 13 infants with pneumonia who were culture and/or PCR negative for U. urealyticum, and 5 infants with pulmonary disease and positive for U. urealyticum by tracheal aspirate and/or lung tissue culture or polymerase chain reaction (PCR). Presence and extent of alveolar macrophages and neutrophils, as well as interstitial lymphocytic infiltration and fibrosis were evaluated. PCR was performed on formalin-fixed, paraffin-embedded lung sections. Additional sections were immunostained for TNF-α. The peripheral total white blood cell counts and absolute neutrophil counts were three-fold higher in infants with U. urealyticum pneumonia than cell counts in infants infected with other organisms. There was a trend toward a predominance of neutrophils in alveoli of non- Ureaplasma pneumonia infants, but a trend toward a predominance of alveolar macrophages in U. urealyticum–infected infants. The most striking finding was the presence of increased interstitial fibrosis in all Ureaplasma-inf ected infants. TNF-α immunoreactive cell density was very low in the gestational controls, but increased in both pneumonia groups. We conclude that persistent lung U. urealyticum infection may contribute to chronic inflammation and early fibrosis in the preterm lung.

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Changes in lung mechanics and reactivity with age after viral bronchiolitis in beagle puppies

Journal of Applied Physiology ◽

10.1152/jappl.1990.69.6.2034 ◽

1990 ◽

Vol 69 (6) ◽

pp. 2034-2042 ◽

Cited By ~ 21

Author(s):

S. F. Quan ◽

R. J. Lemen ◽

M. L. Witten ◽

D. L. Sherrill ◽

R. Grad ◽

...

Keyword(s):

Lung Function ◽

Respiratory Illness ◽

Adenovirus Type ◽

Lung Compliance ◽

Lung Mechanics ◽

Small Airways ◽

Residual Capacity ◽

Regression Slopes ◽

Airways Inflammation

We measured changes with growth in lung function and airway reactivity after acute canine parainfluenza virus type 2 (CPI2, n = 5), canine adenovirus type 2 (CAV2, n = 7), and sequential CAV2-CPI2 (n = 6) infections or no infection (controls, n = 6) in beagle puppies (age approximately 79 days). In the CPI2 and CAV2 groups, a lower respiratory illness developed by day 3 postinfection with clinical recovery by day 14. In the CAV2-CPI2 group, puppies were inoculated initially with CAV2 and 12 days later with CPI2. In this group, illness persisted until day 14 after infection with CPI2. Lung resistance (RL), dynamic (Cdyn) and static (Cst) lung compliance, functional residual capacity (FRC), and responsiveness to aerosolized histamine were measured before infection and at periodic intervals until 239 +/- 43 days of age. Lung function data were analyzed using a longitudinal random effects model. In all groups, FRC, Cst, and Cdyn increased with age. In all infected groups, the regression slopes for Cdyn were steeper than in controls. RL decreased linearly with age without group slope differences. Histamine reactivity increased with age, but there were no differences in slope among groups. Lung pathological studies showed areas of obliterative bronchiolitis and chronic small airways inflammation particularly in the CAV2 and CAV2-CPI2 groups. Thus, viral bronchiolitis produces chronic small airways inflammation in beagle puppies and alters the changes in lung function occurring with growth. Histamine reactivity increases with age and is not modified by viral infection.

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