scholarly journals Effect of Hyaluronic Acid on the Differentiation of Mesenchymal Stem Cells into Mature Type II Pneumocytes

Polymers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 2928
Author(s):  
Francesca Della Sala ◽  
Mario di Gennaro ◽  
Gianluca Lista ◽  
Francesco Messina ◽  
Luigi Ambrosio ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Lung Surfactant ◽  
Repair Process ◽  
Surfactant Protein ◽  
Alveolar Type ◽  
Type Ii ◽  
Type Ii Pneumocytes ◽  
Mature Type ◽  
Pulmonary Damage ◽  
Msc Differentiation

Hyaluronic acid (HA) is an essential component of the extracellular matrix (ECM) of the healthy lung, playing an important role in the structure of the alveolar surface stabilizing the surfactant proteins. Alveolar type II (ATII) cells are the fundamental element of the alveolus, specializing in surfactant production. ATII cells represent the main target of lung external lesion and a cornerstone in the repair process of pulmonary damage. In this context, knowledge of the factors influencing mesenchymal stem cell (MSC) differentiation in ATII cells is pivotal in fulfilling therapeutic strategies based on MSCs in lung regenerative medicine. To achieve this goal, the role of HA in promoting the differentiation of MSCs in mature Type II pneumocytes capable of secreting pulmonary surfactant was evaluated. Results demonstrated that HA, at a specific molecular weight can greatly increase the expression of lung surfactant protein, indicating the ability of HA to influence MSC differentiation in ATII cells.

scholarly journals Role of Phosphocholine Cytidylyltransferase α in Lung Development

2006 ◽  
Vol 27 (3) ◽  
pp. 975-982 ◽  
Author(s):  
Yong Tian ◽  
Ruobing Zhou ◽  
Jerold E. Rehg ◽  
Suzanne Jackowski
Keyword(s):  
Epithelial Cell ◽  
Lung Development ◽  
Cultured Cells ◽  
Lung Surfactant ◽  
Surfactant Protein ◽  
Alveolar Type ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Lamellar Bodies

ABSTRACT Lung development depends upon the differentiation and expansion of a variety of specialized epithelial cell types, including distal type I and type II pneumocytes in the late term. Previous studies have shown a strict dependence on the choline cytidylyltransferase α isoform (CCTα) to mediate membrane phospholipid formation in cultured cells and during preimplantation embryogenesis. CCTα expression is highest in lung, and there has long been speculation about its precise role, due to the dual requirement for phospholipid in proliferating cell membranes and for lung surfactant production from alveolar type II cells. We investigated the function of CCTα in lung development, using an inducible, epithelial cell-specific CCTα knockout mouse line. Deletion of CCTα beginning at embryonic day 7.5 did not restrict lung development but resulted in severe respiratory failure at birth. Alveolar lavage and lung lipid analyses showed significant decreases in the major surfactant phospholipid, dipalmitoyl-phosphatidylcholine. The fatty acids destined for the surfactant phospholipid were redirected to an expanded triglyceride pool. Transcripts encoding type II cell-specific markers were expressed in the knockout mice, indicating the expected progression of differentiation in lung epithelia. However, surfactant protein levels were reduced, with the exception of that for surfactant protein B, which was elevated. Ultrastructural analysis of the type II cells showed Golgi complex abnormalities and aberrant lamellar bodies, which deliver surfactant lipid and protein to the alveolar lumen. Thus, CCTα was not required for the proliferation or differentiation of lung epithelia but was essential for the secretory component of phospholipid synthesis and critical for the proper formation of lamellar bodies and surfactant protein homeostasis.

Surfactant Protein A Stimulates Release of Neutrophil Chemotactic Factors by Alveolar Type II Pneumocytes

Lung ◽  
2010 ◽  
Vol 188 (6) ◽  
pp. 491-497 ◽  
Author(s):  
Mitchell J. Kresch ◽  
Mitchell Block ◽  
Mohammed R. Karim ◽  
Li Zhu ◽  
Naveed Hussain ◽  
...  
Keyword(s):  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Alveolar Type ◽  
Type Ii ◽  
Type Ii Pneumocytes ◽  
Chemotactic Factors

Pollen grains bind to lung alveolar type II cells (A549) via lung surfactant protein A (SP-A)

1993 ◽  
Vol 13 (2) ◽  
pp. 79-90 ◽  
Author(s):  
Rajneesh Malhotra ◽  
John Haurum ◽  
Steffen Thiel ◽  
J. -C. Jensenius ◽  
Robert B. Sim
Keyword(s):  
Lung Surfactant ◽  
Protein A ◽  
A549 Cells ◽  
Pollen Grains ◽  
Cell Types ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Alveolar Type ◽  
Type Ii ◽  
Lung Surfactant Protein

Lung surfactant protein A (SP-A) is the most abundant surfactant-associated protein present in the lung. A receptor for SP-A has been shown to be present on A549 alveolar type II cells and on other cell types, including alveolar macrophage. The SP-A receptor on A549 cells has been identified as the collectin receptor, or C1q receptor, which binds several structurally-related ligands. SP-A contains C-type lectin domains, but the role of carbohydrate binding by SP-A in physiological and pathological phenomena is not yet established. In this paper we report the binding of SP-A to pollen from Populus nigra italica (Lombardy Poplar), Poa pratensis (Kentucky blue grass), Secale cerale (cultivated rye) and Ambrosia elatior (short ragweed). Saturable and concentration dependent binding of SP-A to pollen grains was observed. Interaction of SP-A with pollen grains takes place through waterextractable components, in which the major species present, in Lombardy poplar pollen, are 57 kD and 7 kD (glyco)proteins. The binding of SP-A to pollen grains and their aqueous extracts was calcium ion dependent and was inhibited by mannose, and is therefore mediated by the lectin domain. Binding of SP-A to pollen grains was found to mediate adhesion of pollen grains to A549 cells. The results suggest that pollen grains or other carbohydrate-bearing particles (e. g. microorganisms) could potentially interact with different cell types via the collectin receptor (C1q Receptor) in the presence of SP-A.

scholarly journals Role of the PI3-kinase signaling pathway in trafficking of the surfactant protein A receptor P63 (CKAP4) on type II pneumocytes

2010 ◽  
Vol 299 (6) ◽  
pp. L794-L807 ◽  
Author(s):  
Altaf S. Kazi ◽  
Jian-Qin Tao ◽  
Sheldon I. Feinstein ◽  
Li Zhang ◽  
Aron B. Fisher ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Protein A ◽  
Surfactant Protein ◽  
Pi3 Kinase ◽  
Surfactant Protein A ◽  
Type Ii Cells ◽  
Type Ii ◽  
Type Ii Pneumocytes ◽  
Kinase Signaling Pathway ◽  
Stimulation Of

Surfactant protein A (SP-A) plays an important role in the maintenance of lung lipid homeostasis. Previously, an SP-A receptor, P63 (CKAP4), on type II pneumocyte plasma membranes (PM) was identified by chemical cross-linking techniques. An antibody to P63 blocked the specific binding of SP-A to pneumocytes and the ability of SP-A to regulate surfactant secretion. The current report shows that another biological activity of SP-A, the stimulation of surfactant uptake by pneumocytes, is inhibited by P63 antibody. cAMP exposure resulted in enrichment of P63 on the cell surface as shown by stimulation of SP-A binding, enhanced association of labeled P63 antibody with type II cells, and promotion of SP-A-mediated liposome uptake, all of which were inhibited by competing P63 antibody. Incubation of A549 and type II cells with SP-A also increased P63 localization on the PM. The phosphatidylinositol 3-kinase (PI3-kinase) signaling pathway was explored as a mechanism for the transport of this endoplasmic reticulum (ER)-resident protein to the PM. Treatment with LY-294002, an inhibitor of the PI3-kinase pathway, prevented the SP-A-induced PM enrichment of P63. Exposure of pneumocytes to SP-A or cAMP activated Akt (PKB). Blocking either PI3-kinase or Akt altered SP-A-mediated lipid turnover. The data demonstrate an important role for the PI3-kinase-Akt pathway in intracellular transport of P63. The results add to the growing body of evidence that P63 is critical for SP-A receptor-mediated interactions with type II pneumocytes and the resultant regulation of surfactant turnover.

Nitric oxide decreases surfactant protein gene expression in primary cultures of type II pneumocytes

2005 ◽  
Vol 288 (5) ◽  
pp. L950-L957 ◽  
Author(s):  
Jae W. Lee ◽  
Robert F. Gonzalez ◽  
Cheryl J. Chapin ◽  
Justin Busch ◽  
Jeffrey R. Fineman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Protein Gene ◽  
Surfactant Protein ◽  
Model Systems ◽  
Cell Phenotype ◽  
Mrna Levels ◽  
Type Ii ◽  
Endothelin 1 ◽  
Type Ii Pneumocytes

Inhaled nitric oxide (NO) is a selective pulmonary vasodilator effective in treating persistent pulmonary hypertension in newborns and in infants following congenital heart disease surgery. Recently, multiple in vivo and in vitro studies have shown a negative effect of NO on surfactant activity as well as surfactant protein gene expression. Although the relationship between NO and surfactant has been studied previously, the data has been hard to interpret due to the model systems used. The objective of the current study was to characterize the effect of NO on surfactant protein gene expression in primary rat type II pneumocytes cultured on a substratum that promoted the maintenance of type II cell phenotype. Exposure to a NO donor, S-nitroso-N-acetylpenicillamine (SNAP), decreased surfactant protein (SP)-A, (SP)-B, and (SP)-C mRNA levels in type II pneumocytes in a time- and dose-dependent manner. The effect was mediated in part by an increase in endothelin-1 secretion and a decrease in the intracellular messenger, phosphorylated ERK1/2 mitogen-activated protein kinases (MAPK). Exposing type II pneumocytes to endothelin-1 receptor antagonists PD-156707 or bosentan before exposure to SNAP partially prevented the decrease in surfactant protein gene expression. The results showed that NO mediated the decrease in surfactant protein gene expression at least in part through an increase in endothelin-1 secretion and a decrease in phosphorylated ERK1/2 MAPKs.

Exposure of surfactant protein A to ozone in vitro and in vivo impairs its interactions with alveolar cells

1992 ◽  
Vol 262 (1) ◽  
pp. L63-L68 ◽  
Author(s):  
R. S. Oosting ◽  
J. F. Van Iwaarden ◽  
L. Van Bree ◽  
J. Verhoef ◽  
L. M. Van Golde ◽  
...  
Keyword(s):  
Superoxide Anion ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Alveolar Type ◽  
Type Ii ◽  
Superoxide Anion Production ◽  
Anion Production

This study focused on the question of whether exposure of surfactant protein A (SP-A) to ozone affected properties of this protein that may be involved in regulating alveolar type II cell and alveolar macrophage functions. In vitro exposure of human or canine SP-A to ozone reduced the ability of this protein to inhibit phorbol-ester induced secretion of [3H]phosphatidylcholine by alveolar type II cells in culture. Ozone-exposed human SP-A showed a decreased ability to enhance phagocytosis of herpes simplex virus and to stimulate superoxide anion production by alveolar macrophages. Experiments with elastase showed that ozone-exposed canine SP-A was more susceptible to proteolysis. A conformational change of the protein could underlie this phenomenon. Surfactant isolated from ozone-exposed rats (0.4 ppm ozone for 12 h) was also less able to stimulate superoxide anion production by alveolar macrophages than surfactant from control rats, which suggested that SP-A in vivo was also susceptible to ozone. The results of this study suggest that SP-A-alveolar cell interactions can be inhibited by ozone exposure, which may contribute to the toxicity of ozone in the lungs.

Uptake of a natural surfactant and increased delivery of small organic anions into type II pneumocytes

2001 ◽  
Vol 281 (1) ◽  
pp. L144-L154 ◽  
Author(s):  
Matthias Griese ◽  
Astrid Baatz ◽  
Julia Beck ◽  
Barbara Deubzer
Keyword(s):  
Sodium Salt ◽  
Targeted Delivery ◽  
Lung Surfactant ◽  
Organic Anions ◽  
Type Ii Cells ◽  
Type Ii ◽  
Natural Surfactant ◽  
Type Ii Pneumocytes ◽  
Acid Sodium Salt

The uptake of natural lung surfactant into differentiated type II cells may be used for the targeted delivery of other molecules. The fluorescent anion pyranine [hydroxypyren-1,3,6-trisulfonic acid, sodium salt (HPTS)] was incorporated into a bovine surfactant labeled with [3H]dipalmitoylphosphatidylcholine ([3H]DPPC). The uptake of [3H]DPPC and of HPTS increased with time of incubation and concentration, decreased with the size of the vesicles used, and was stimulated by 8-bromo-cAMP and partially inhibited by hypertonic sucrose. However, the amount of HPTS uptake was ∼100 times smaller than that of [3H]DPPC. This large difference was due to a more rapid regurgitation of some of the HPTS from the cells but not to leakage from the surfactant before uptake. The acidification of the internalized surfactant increased linearly over 90 min to 7.13, and after 24 h, a pH of 6.83 was measured. In conclusion, after internalization of a double-labeled natural surfactant, the lipid moieties were accumulated in relation to the anions, which were targeted to a compartment not very acidic and in part rapidly expelled from the 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)

scholarly journals Transitional human alveolar type II epithelial cells suppress extracellular matrix and growth factor gene expression in lung fibroblasts

2019 ◽  
Vol 317 (2) ◽  
pp. L283-L294 ◽  
Author(s):  
Kelly A. Correll ◽  
Karen E. Edeen ◽  
Rachel L. Zemans ◽  
Elizabeth F. Redente ◽  
Karina A. Serban ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Surfactant Protein ◽  
Lung Fibroblasts ◽  
Alveolar Type ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Type Ii Cells ◽  
I Cells

Epithelial-fibroblast interactions are thought to be very important in the adult lung in response to injury, but the specifics of these interactions are not well defined. We developed coculture systems to define the interactions of adult human alveolar epithelial cells with lung fibroblasts. Alveolar type II cells cultured on floating collagen gels reduced the expression of type 1 collagen (COL1A1) and α-smooth muscle actin (ACTA2) in fibroblasts. They also reduced fibroblast expression of hepatocyte growth factor (HGF), fibroblast growth factor 7 (FGF7, KGF), and FGF10. When type II cells were cultured at an air-liquid interface to maintain high levels of surfactant protein expression, this inhibitory activity was lost. When type II cells were cultured on collagen-coated tissue culture wells to reduce surfactant protein expression further and increase the expression of some type I cell markers, the epithelial cells suppressed transforming growth factor-β (TGF-β)-stimulated ACTA2 and connective tissue growth factor (CTGF) expression in lung fibroblasts. Our results suggest that transitional alveolar type II cells and likely type I cells but not fully differentiated type II cells inhibit matrix and growth factor expression in fibroblasts. These cells express markers of both type II cells and type I cells. This is probably a normal homeostatic mechanism to inhibit the fibrotic response in the resolution phase of wound healing. Defining how transitional type II cells convert activated fibroblasts into a quiescent state and inhibit the effects of TGF-β may provide another approach to limiting the development of fibrosis after alveolar injury.

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