scholarly journals Alveolar Type II Cells and Pulmonary Surfactant in COVID-19 Era

2021 ◽  
pp. S195-S208
Author(s):  
A CALKOVSKA ◽  
M KOLOMAZNIK ◽  
V CALKOVSKY
Keyword(s):  
Pulmonary Surfactant ◽  
Lung Mechanics ◽  
Exogenous Surfactant ◽  
Lung Edema ◽  
Target Cells ◽  
Alveolar Type ◽  
Respiratory Pathogens ◽  
Type Ii ◽  
Novel Coronavirus

In this review, we discuss the role of pulmonary surfactant in the host defense against respiratory pathogens, including novel coronavirus SARS-CoV-2. In the lower respiratory system, the virus uses angiotensin-converting enzyme 2 (ACE2) receptor in conjunction with serine protease TMPRSS2, expressed by alveolar type II (ATII) cells as one of the SARS-CoV-2 target cells, to enter. ATII cells are the main source of surfactant. After their infection and the resulting damage, the consequences may be severe and may include injury to the alveolar-capillary barrier, lung edema, inflammation, ineffective gas exchange, impaired lung mechanics and reduced oxygenation, which resembles acute respiratory distress syndrome (ARDS) of other etiology. The aim of this review is to highlight the key role of ATII cells and reduced surfactant in the pathogenesis of the respiratory form of COVID-19 and to emphasize the rational basis for exogenous surfactant therapy in COVID-19 ARDS patients.

scholarly journals Activation of the SARS-CoV-2 receptor Ace2 by cytokines through pan JAK-STAT enhancers

2020 ◽  
Author(s):  
Lothar Hennighausen ◽  
Hye Kyung Lee
Keyword(s):  
Mammary Tissue ◽  
Cytokine Signaling ◽  
Target Cells ◽  
The Novel ◽  
Type Ii ◽  
Alveolar Cells ◽  
Type Ii Pneumocytes ◽  
Pregnancy And Lactation ◽  
Novel Coronavirus

SummaryACE2, in concert with the protease TMPRSS2, binds the novel coronavirus SARS-CoV-2 and facilitates its cellular entry. The ACE2 gene is expressed in SARS-CoV-2 target cells, including Type II Pneumocytes (Ziegler, 2020), and is activated by interferons. Viral RNA was also detected in breast milk (Wu et al., 2020), raising the possibility that ACE2 expression is under the control of cytokines through the JAK-STAT pathway. Here we show that Ace2 expression in mammary tissue is induced during pregnancy and lactation, which coincides with the establishment of a candidate enhancer. The prolactin-activated transcription factor STAT5 binds to tandem sites that coincide with activating histone enhancer marks and additional transcription components. The presence of pan JAK-STAT components in mammary alveolar cells and in Type II Pneumocytes combined with the autoregulation of both STAT1 and STAT5 suggests a prominent role of cytokine signaling pathways in cells targeted by SARS-CoV-2.

Stimulation of surfactant exocytosis in primary alveolar type II cells by A. fumigatus

2020 ◽  
Author(s):  
Natalia Schiefermeier-Mach ◽  
Susanne Perkhofer ◽  
Lea Heinrich ◽  
Thomas Haller
Keyword(s):  
Pulmonary Surfactant ◽  
Defense Mechanisms ◽  
Alveolar Epithelium ◽  
Fungal Growth ◽  
Alveolar Type ◽  
Fungal Culture ◽  
Type Ii ◽  
Airborne Spores ◽  
Upper Airways ◽  
Cellular Effects

Abstract Aspergillus fumigatus is an opportunistic fungal pathogen with small airborne spores (conidia) that may escape clearance by upper airways and directly impact the alveolar epithelium. Consequently, innate alveolar defense mechanisms are being activated, including professional phagocytosis by alveolar macrophages, recruitment of circulating neutrophils and probably enhanced secretion of pulmonary surfactant by the alveolar type II (AT II) cells. However, no data are available in support of the latter hypothesis. We therefore used a coculture model of GFP-Aspergillus conidia with primary rat AT II cells and studied fungal growth, cellular Ca2+ homeostasis, and pulmonary surfactant exocytosis by live cell video microscopy. We observed all stages of fungal development, including reversible attachment, binding and internalization of conidia as well as conidial swelling, formation of germ tubes and outgrowth of hyphae. In contrast to resting conidia, which did not provoke immediate cellular effects, metabolically active conidia, fungal cellular extracts (CE) and fungal culture filtrates (CF) prepared from swollen conidia caused a Ca2+-independent exocytosis. Ca2+ signals of greatly varying delays, durations and amplitudes were observed by applying CE or CF obtained from hyphae of A. fumigatus, suggesting compounds secreted by filamentous A. fumigatus that severely interfere with AT II cell Ca2+ homeostasis. The mechanisms underlying the stimulatory effects, with respect to exocytosis and Ca2+ signaling, are unclear and need to be identified.

Requirements for extracellular metabolism of pulmonary surfactant: tentative identification of serine protease

1992 ◽  
Vol 262 (4) ◽  
pp. L446-L453 ◽  
Author(s):  
N. J. Gross ◽  
R. M. Schultz
Keyword(s):  
Serine Protease ◽  
Surface Area ◽  
Pulmonary Surfactant ◽  
Lamellar Body ◽  
Alveolar Epithelium ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Ph Optimum

Pulmonary alveolar surfactant is secreted by the alveolar epithelium in the form of lamellar bodylike structures that evolve sequentially into tubular myelin and vesicular forms that can be separated by centrifugation. Using an in vitro procedure by which the extracellular metabolism of pulmonary surfactant can be mimicked, namely cyclic variation in surface area, we previously reported that serine protease activity, which we called “convertase,” was required for the conversion of tubular myelin to the vesicular form. In the present studies we explored the biochemical requirements of this activity and sought the enzyme in alveolar products. Convertase activity has unusual requirements; in addition to being dependent on repetitive variations in surface area (cycling), it requires the presence of a high g fraction of lung secretions that is heat stable and not inhibitable by diisopropyl fluorophosphate (DFP) or alpha 1-antitrypsin, both typical serine protease inhibitors. The enzyme does not require calcium ions and has a pH optimum of 7.4. Convertase appears to be a component of surfactant itself because the ability of purified surfactant to convert to the vesicular form on cycling is impaired by pretreating it with DFP. A protein of Mr 75,000 that reacts with DFP and is heat sensitive was found in alveolar lavage, lamellar body preparations, and lung homogenate. It copurifies with lung surfactant in sucrose gradients. A similar DFP-reactive protein was observed in stable human neoplastic peripheral airway cell lines that express type II properties, suggesting that it may be a product of type II cells. We tentatively conclude that surfactant convertase is a 75,000 serine protease that is closely associated with surfactant phospholipid and that may be a product of alveolar type II cells.

Pulmonary surfactant protein A-mediated uptake of phosphatidylcholine by alveolar type II cells

1993 ◽  
Vol 265 (2) ◽  
pp. L193-L199 ◽  
Author(s):  
A. Tsuzuki ◽  
Y. Kuroki ◽  
T. Akino
Keyword(s):  
Pulmonary Surfactant ◽  
Protein A ◽  
Lamellar Body ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Lamellar Bodies ◽  
Pulmonary Surfactant Protein

Pulmonary surfactant protein A (SP-A)-mediated uptake of phosphatidylcholine (PC) by alveolar type II cells was investigated. SP-A enhanced the uptake of liposomes containing dipalmitoylphosphatidylcholine (DPPC), 1-palmitoyl-2-linoleoyl phosphatidylcholine (PLPC), or 1,2-dihexadecyl-sn-glycero-3-phosphocholine (DPPC-ether), a diether analogue of DPPC, but about twice as much DPPC was taken up by type II cells as PLPC or DPPC-ether. When subcellular distribution was analyzed, 51.3 +/- 2.9% (mean +/- SD, n = 3) of cell-associated radiolabeled DPPC was recovered in the lamellar body-rich fraction in the presence of SP-A, whereas only 19.3 +/- 1.9% (mean +/- SD, n = 3) was found to this fraction in the absence of SP-A. When type II cells were incubated either with DPPC at 0 degree C or with DPPC-ether at 37 degrees C, or no cells were included, low proportions of the cell-associated lipids were present in the fractions corresponding to lamellar bodies even in the presence of SP-A. Anti-SP-A antibody significantly reduced the radioactivity incorporated into the lamellar body fraction. Phosphatidylcholine that had been incorporated into lamellar bodies remained largely intact when SP-A was present. Subcellular fractionations of type II cells with radiolabeled SP-A and DPPC revealed that the sedimentation characteristics of cell-associated SP-A are different from those of DPPC, although a small broad peak of radiolabeled SP-A was found in the lamellar body fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

An En Bloc Staining Protocol Improves The Preservation of Lamellar Bodies in Alveolar Type II Epithelial Cells for Transgenic Mice Expressing Modified Pulmonary Surfactant Protein B

1998 ◽  
Vol 4 (S2) ◽  
pp. 852-853
Author(s):  
C.-L. Na ◽  
D. C. Beck ◽  
J. S. Breslin ◽  
S. E. Wert ◽  
T. E. Weaver
Keyword(s):  
Pulmonary Surfactant ◽  
Surfactant Protein ◽  
Alveolar Type ◽  
Type Ii ◽  
Lamellar Bodies ◽  
En Bloc ◽  
Surfactant Protein B ◽  
Staining Protocol ◽  
Pulmonary Surfactant Protein B ◽  
Pulmonary Surfactant Protein

The extraction of lipids and phospholipids during dehydration and plastic embedding steps results in poor preservation of the phospholipid rich lamellar bodies (LB) in alveolar type II epithelial cells. To achieve better retention of phospholipids, we combined inflation fixation and an en bloc staining protocol using 4% aqueous uranyl acetate (UA), thereby improving the preservation of the LBs for both the wild type and transgenic mice expressing modified pulmonary surfactant protein B (SP-B; Akinbi et al., 1997).Lungs of 6-8 week-old mice were inflation fixed (Bunkingham and Weyder, 1981) with ice cold 2% paraformaldehye and 2% glutaraldehyde in 0.1 M sodium cacodylate buffer (SCB), pH 7.3, postfixed in fresh fixative at 4 °C overnight, incubated with 1% osmium tetroxide in 0.1 M SCB at room temperature for 2 hours, and stained en bloc with 4% aqueous UA overnight.

Role of Peripheral Benzodiazepine Receptors on Secretion of Surfactant in Guinea Pig Alveolar Type II Cells

1999 ◽  
Vol 19 (5) ◽  
pp. 461-471 ◽  
Author(s):  
Salil K. Das ◽  
Shyamali Mukherjee
Keyword(s):  
Pulmonary Surfactant ◽  
Benzodiazepine Receptors ◽  
Alveolar Epithelium ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Type Ii Cells ◽  
Peripheral Tissues ◽  
Dipalmitoyl Phosphatidylcholine ◽  
Peripheral Benzodiazepine Receptors

Granular type II cells located in the alveolar epithelium synthesize and secrete pulmonary surfactant and have specialized ion transport system. Alveolar type II cells are stimulated to secrete pulmonary surfactant by a variety of agonists. One mechanism by which extracellular signals are perceived by cells is the mobilization of intracellular Ca2+. Peripheral benzodiazepine receptors (PBRs) are present in both peripheral tissues and central nervous system. We have previously reported the presence of high density PBRs in lung and alveolar type II cells. It is known that both PBRs and beta-adrenergic receptors (beta-ARs) play an important role in cellular Ca2+ transport. Furthermore, we have suggested earlier that PBRs are someway functionally associated with the beta-ARs. The objective of the present study was to determine whether PBRs play any role in the secretion of surfactant by alveolar type II cells. Alveolar type II cells were isolated from normal weanling guinea pigs by panning method and incubated with 3H-palmitic acid in minimum essential medium to synthesize labelled dipalmitoyl phosphatidylcholine (DPPC). After washing, the cells were treated at 37°C for one hour with 10 μM isoproterenol (IP) in the presence and absence of 10 μM Ro 5-4864, an agonist for PBRs. After one hour, the release of labelled DPPC in the medium was analyzed. The control cells released DPPC without any addition of a ligand. However, the treatment of cells with IP, Ro 5-4864 and IP + Ro 5-4864 caused 24, 52 and 171% increase in the secretion of DPPC, respectively. In another experiment, type II cells were loaded with Fura-2 dye and treated with either IP or epineprine or Ro 5-4864. Both isoproterenol and epinephrine caused a significant increase in the level of cytosolic free Ca2+. However, Ro 5-4864 caused not only a decrease in the level of cytosolic free Ca2+ but also counteracted the stimulatory effect of IP. This may suggest that while ligands for ARs stimulate Ca2+ release into cytosol, the ligand for PBRs stimulates efflux of Ca2+ in alveolar type cells. Thus, the increased secretion of surfactant by the ligand of PBRs in alveolar type II cells may be mediated through its effects on increased Ca2+ efflux.

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