Susceptibility To Alveolar Type II Cell Apoptosis And Pulmonary Fibrosis In Naturally Occurring Hermansky Pudlak Syndrome Mice Is Not Associated With Endoplasmic Reticulum Stress

Background: The pathogenetic steps leading to Covid-19 interstitial pneumonia remain to be clarified. Most postmortem studies to date reveal diffuse alveolar damage as the most relevant histologic pattern. Antemortem lung biopsy may however provide more precise data regarding the earlier stages of the disease, providing a basis for novel treatment approaches. Objectives: To ascertain the morphological and immunohistochemical features of lung samples obtained in patients with moderate Covid-19 pneumonia. Methods: Transbronchial lung cryobiopsy was carried out in 12 Covid-19 patients within 20 days of symptom onset. Results: Histopathologic changes included spots of patchy acute lung injury with alveolar type II cell hyperplasia, with no evidence of hyaline membranes. Strong nuclear expression of phosphorylated STAT3 was observed in >50% of AECII. Interalveolar capillaries showed enlarged lumen and were in part arranged in superposed rows. Pulmonary venules were characterized by luminal enlargement, thickened walls, and perivascular CD4+ T-cell infiltration. A strong nuclear expression of phosphorylated STAT3, associated with PD-L1 and IDO expression, was observed in endothelial cells of venules and interstitial capillaries. Alveolar spaces macrophages exhibited a peculiar phenotype (CD68, CD11c, CD14, CD205, CD206, CD123/IL3AR, and PD-L1). Conclusions: Morphologically distinct features were identified in early stages of Covid-19 pneumonia, with epithelial and endothelial cell abnormalities different from either classical interstitial lung diseases or diffuse alveolar damage. Alveolar type II cell hyperplasia was a prominent event in the majority of cases. Inflammatory cells expressed peculiar phenotypes. No evidence of hyaline membranes and endothelial changes characterized by IDO expression might in part explain the compliance and the characteristic pulmonary vasoplegia observed in less-advanced Covid-19 pneumonia.

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Quantitative Analysis of Alveolar Type II Cell Tumors in Mice by Whole Lung Serial and Step Sections

Toxicologic Pathology ◽

10.1177/0192623389017004201 ◽

1989 ◽

Vol 17 (4_part_2) ◽

pp. 737-742 ◽

Cited By ~ 13

Author(s):

Sabine Rehm ◽

Jerrold M. Ward

Keyword(s):

Mouse Lung ◽

Alveolar Type ◽

Type Ii ◽

Serial Sections ◽

Feasible Method ◽

Alveolar Type Ii Cell ◽

Microscopic Lesion ◽

Entire Lung ◽

Type Ii Cell ◽

Mouse Lungs

Alveolar type II cell tumors were induced transplacentally by intraperitoneal injection of pregnant C3H/HeNCr MTV– or Swiss Webster mice with N-nitrosoethylurea at a dose of 0.5 mmol/kg and 0.74 mmol/kg. At different time points after birth (1–32 weeks), the entire lungs from 40 of the male offspring were inflated with Bouin's fixative, separated into lobes, and sectioned at 5 μm serially to detect every microscopic lesion. Results were compared with those obtained from examining only every 10th, 20th, or a single mid-level section from the same material. On average, 150 serial sections were prepared per mouse lung. Initially, only purely solid/alveolar or purely tubulopapillary types were observed but with tumor progression, papillary structures developed within solid tumors resulting in mixed neoplasms. Analyzing mouse lungs in step sections of every 10th section (50–60 μm), 5/238 (2%) of the tumors were missed, in step sections of every 20th section (100–120 μm), 16/238 (7%) of the tumors were not detected and usually less than half of the tumors were seen in the single mid-level section. The approximate size of the neoplasms is indicated by the total number of sections per tumor. The dimensions of tumors evaluated with step sections of 10 or 20 were comparable to the size observed with serial sections. It is concluded that the evaluation of mouse lung tumors in steps of approximately 50 μm is basically equivalent to the study of serial sections and appears to be a feasible method to assess the complete incidence, histological type, and size of all proliferative processes throughout the entire lung.

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