Regulation of alveolar epithelial cell phenotypes in fetal sheep: roles of cortisol and lung expansion

2004 ◽  
Vol 287 (6) ◽  
pp. L1207-L1214 ◽  
Author(s):  
Sharon J. Flecknoe ◽  
Rochelle E. Boland ◽  
Megan J. Wallace ◽  
Richard Harding ◽  
Stuart B. Hooper
Keyword(s):  
Epithelial Cell ◽  
Alveolar Epithelial Cell ◽  
Fetal Lung ◽  
Saline Infusion ◽  
Type I ◽  
Mrna Levels ◽  
Type Ii ◽  
Fetal Sheep ◽  
Alveolar Epithelial ◽  
Lung Expansion

Our aim was to determine whether cortisol's effect on alveolar epithelial cell (AEC) phenotypes in the fetus is mediated via a sustained alteration in lung expansion. Chronically catheterized fetal sheep were exposed to 1) saline infusion, 2) cortisol infusion (122–131 days' gestation, 1.5–4.0 mg/day), 3) saline infusion plus reduced lung expansion, or 4) cortisol infusion plus reduced lung expansion. The proportions of type I and II AECs were determined by electron microscopy, and surfactant protein (SP)-A, -B, and -C mRNA levels were determined by Northern blot analysis. Cortisol infusions significantly increased type II AEC proportions (to 38.2 ± 2.2%), compared with saline-infused fetuses (23.8 ± 2.4%), and reduced type I AEC proportions (to 59.0 ± 2.2%), compared with saline-infused fetuses (70.4 ± 2.4%). Reduced lung expansion also increased type II AEC proportions (to 52.9 ± 3.5%) and decreased type I AEC proportions (to 34.2 ± 3.7%), compared with control, saline-infused fetuses. The infusion of cortisol into fetuses exposed to reduced lung expansion tended to further increase type II (to 60.3 ± 2.1%, P = 0.066) and reduce type I AEC (to 26.6 ± 2.3%, P = 0.07) proportions. SP-A, -B, and -C mRNA levels changed in parallel with the changes in type II AEC proportions. These results indicate that cortisol alters the proportion of type I and type II AECs via a mechanism unrelated to the degree of fetal lung expansion. However, reductions in fetal lung expansion appear to have a greater impact on the proportion of AECs than cortisol.

Changes in alveolar epithelial cell proportions during fetal and postnatal development in sheep

2003 ◽  
Vol 285 (3) ◽  
pp. L664-L670 ◽  
Author(s):  
S. J. Flecknoe ◽  
M. J. Wallace ◽  
M. L. Cock ◽  
R. Harding ◽  
S. B. Hooper
Keyword(s):  
Epithelial Cell ◽  
Important Determinant ◽  
Alveolar Epithelial Cell ◽  
Surfactant Protein ◽  
Type I ◽  
Mrna Levels ◽  
Type Ii ◽  
Alveolar Epithelial ◽  
Lung Expansion ◽  
Birth Type

Basal lung expansion is an important determinant of alveolar epithelial cell (AEC) phenotype in the fetus. Because basal lung expansion increases toward term and is reduced after birth, we hypothesized that these changes would be associated with altered proportions of AECs. AEC proportions were calculated with electron microscopy in fetal and postnatal sheep. Type I AECs increased from 4.8 ± 1.3% at 91 days to 63.0 ± 3.6% at 111 days of gestation, remained at this level until term, and decreased to 44.8 ± 1.8% after birth. Type II AECs increased from 4.3 ± 1.5% at 111 days to 29.6 ± 4.1% at 128 days of gestation, remained at this level until term, and then increased to 52.9 ± 1.5% after birth. Surfactant protein (SP)-A, -B and -C mRNA levels increased with increasing gestational age before birth, but the changes in SP expression after birth were inconsistent. Thus before birth type I AECs predominate, whereas after birth type II AECs predominate, possibly due to the reduction in basal lung expansion associated with the entry of air into the lungs.

scholarly journals Role of collagenase in mediating in vitro alveolar epithelial wound repair

1999 ◽  
Vol 112 (2) ◽  
pp. 243-252
Author(s):  
E. Planus ◽  
S. Galiacy ◽  
M. Matthay ◽  
V. Laurent ◽  
J. Gavrilovic ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Epithelial Cell ◽  
Type I Collagen ◽  
Alveolar Epithelial Cell ◽  
Cell Monolayer ◽  
Type I ◽  
Type Ii ◽  
Alveolar Epithelial

Type II pneumocytes are essential for repair of the injured alveolar epithelium. The effect of two MMP collagenases, MMP-1 and MMP-13 on alveolar epithelial repair was studied in vitro. The A549 alveolar epithelial cell line and primary rat alveolar epithelial cell cultures were used. Cell adhesion and cell migration were measured with and without exogenous MMP-1. Wound healing of a cell monolayer of rat alveolar epithelial cell after a mechanical injury was evaluated by time lapse video analysis. Cell adhesion on type I collagen, as well as cytoskeleton stiffness, was decreased in the presence of exogenous collagenases. A similar decrease was observed when cell adhesion was tested on collagen that was first incubated with MMP-1 (versus control on intact collagen). Cell migration on type I collagen was promoted by collagenases. Wound healing of an alveolar epithelial cell monolayer was enhanced in the presence of exogenous collagenases. Our results suggest that collagenases could modulate the repair process by decreasing cell adhesion and cell stiffness, and by increasing cell migration on type I collagen. Collagen degradation could modify cell adhesion sites and collagen degradation peptides could induce alveolar type II pneumocyte migration. New insights regarding alveolar epithelial cell migration are particularly relevant to investigate early events during alveolar epithelial repair following lung injury.

scholarly journals Simultaneous isolation of endothelial and alveolar epithelial type I and type II cells during mouse lung development in the absence of a transgenic reporter

2020 ◽  
Vol 318 (4) ◽  
pp. L619-L630 ◽  
Author(s):  
Yves Donati ◽  
Sanja Blaskovic ◽  
Isabelle Ruchonnet-Métrailler ◽  
Josefina Lascano Maillard ◽  
Constance Barazzone-Argiroffo
Keyword(s):  
Epithelial Cell ◽  
De Novo ◽  
Morphological Changes ◽  
Alveolar Epithelial Cell ◽  
Mouse Lung ◽  
Cell Populations ◽  
Type I ◽  
Type Ii ◽  
Alveolar Cells ◽  
Alveolar Epithelial

Mouse lung developmental maturation and final alveolarization phase begin at birth. During this dynamic process, alveolar cells modify their morphology and anchorage to the extracellular matrix. In particular, alveolar epithelial cell (AEC) type I undergo cytoplasmic flattening and folding to ensure alveoli lining. We developed FACS conditions for simultaneous isolation of alveolar epithelial and endothelial cells in the absence of specific reporters during the early and middle alveolar phase. We evidenced for the first time a pool of extractable epithelial cell populations expressing high levels of podoplanin at postnatal day (pnd)2, and we confirmed by RT-qPCR that these cells are already differentiated but still immature AEC type I. Maturation causes a decrease in isolation yields, reflecting the morphological changes that these cell populations are undergoing. Moreover, we find that major histocompatibility complex II (MHCII), reported as a good marker of AEC type II, is poorly expressed at pnd2 but highly present at pnd8. Combined experiments using LysoTracker and MHCII demonstrate the de novo acquisition of MCHII in AEC type II during lung alveolarization. The lung endothelial populations exhibit FACS signatures from vascular and lymphatic compartments. They can be concomitantly followed throughout alveolar development and were obtained with a noticeable increased yield at the last studied time point (pnd16). Our results provide new insights into early lung alveolar cell isolation feasibility and represent a valuable tool for pure AEC type I preparation as well as further in vitro two- and three-dimensional studies.

Integrin mediation of alveolar epithelial cell migration on fibronectin and type I collagen

1997 ◽  
Vol 273 (1) ◽  
pp. L134-L141 ◽  
Author(s):  
H. J. Kim ◽  
C. A. Henke ◽  
S. K. Savik ◽  
D. H. Ingbar
Keyword(s):  
Cell Migration ◽  
Epithelial Cell ◽  
Type I Collagen ◽  
Alveolar Epithelial Cell ◽  
Matrix Proteins ◽  
Type I ◽  
Type Ii ◽  
Alveolar Epithelial ◽  
Beta 1 Integrin ◽  
Alpha V Beta 3

Acute lung injury leads to type I alveolar epithelial cell (AEC) death, denudation of the alveolar basement membrane, and formation of an alveolar provisional matrix from fibronectin, fibrinogen, and type I collagen. The provisional matrix provides a scaffold for alveolar repair. To restore normal lung architecture, surviving type II AECs must reepithelialize denuded alveoli. We examined whether AECs migrate on provisional matrix proteins and whether integrins mediate this migration using a Boyden chemotaxis chamber. Cultured AECs migrated on fibronectin-coated filters by haptotaxis (defined as movement on a solid-phase substrate) more than one type I collagen-coated filters, and they did not migrate on fibrinogen-coated filters. Soluble fibronectin augmented migration on type I collagen-coated filters, but not on fibronectin-coated filters. Anti-alpha v beta 3-integrin monoclonal antibody (MAb) inhibited migration on substrate-bound fibronectin by 62-77%, whereas anti-beta 1-integrin MAb inhibited migration by 48%. Anti-alpha 2-integrin MAb almost completely inhibited migration on substrate-bound type I collagen, but not on fibronectin. The novel findings in this study are as follows: 1) AECs migrate by haptotaxis more effectively on substrate-bound fibronectin than on type I collagen; 2) alpha v beta 3- and beta 1-integrins partially mediate AEC haptotaxis on fibronectin; and 3) the alpha 2 beta 1-integrin mediates AEC migration on type I collagen. These results support the importance of type II cell migration on provisional matrix proteins during repair of lung injury.

Association of ICAM-1 with the cytoskeleton in rat alveolar epithelial cells in primary culture

1996 ◽  
Vol 271 (5) ◽  
pp. L707-L718 ◽  
Author(s):  
W. W. Barton ◽  
S. E. Wilcoxen ◽  
P. J. Christensen ◽  
R. Paine
Keyword(s):  
Endothelial Cells ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Alveolar Epithelial Cell ◽  
Inflammatory Cells ◽  
Alveolar Epithelial Cells ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Epithelial

Intercellular adhesion molecule-1 ICAM-1) is a transmembrane adhesion protein that is expressed constitutively on the apical surface of type I cells in vivo and on type II cells in vitro as they spread in culture, assuming type I cell-like characteristics. To investigate the possible interaction of ICAM-1 with the alveolar epithelial cell cytoskeleton, rat type II cells in primary culture were extracted with nonionic detergent, and residual ICAM-1 associated with the cytoskeletal remnants was determined using immunofluorescence microscopy, immunoprecipitation, and cell-based enzyme-linked immunosorbent assay. A large fraction of alveolar epithelial cell ICAM-1 remained associated with the cytoskeleton after detergent extraction, whereas two other transmembrane molecules, transferrin receptor and class II major histocompatibility complex, were completely removed. ICAM-1 was redistributed on the cell surface after the disruption of actin filaments with cytochalasin B, suggesting interaction with the actin cytoskeleton. In contrast, ICAM-1 was completely detergent soluble in rat pulmonary artery endothelial cells, human umbilical vein endothelial cells, and rat alveolar macrophages. The association of ICAM-1 with the alveolar epithelial cell cytoskeleton was not altered after stimulation with inflammatory cytokines. However, detergent resistant ICAM-1 was significantly increased after crosslinking of ICAM-1 on the cell surface, suggesting that this cytoskeletal association may be modulated by interactions of alveolar epithelial cells with inflammatory cells. The association of ICAM-1 with the cytoskeleton in alveolar epithelial cells may provide a fixed intermediary between mobile inflammatory cells and the alveolar surface.

VDUP1: a potential mediator of expansion-induced lung growth and epithelial cell differentiation in the ovine fetus

2006 ◽  
Vol 290 (2) ◽  
pp. L250-L258 ◽  
Author(s):  
C. E. Filby ◽  
S. B. Hooper ◽  
F. Sozo ◽  
V. A. Zahra ◽  
S. J. Flecknoe ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Differentiation ◽  
Epithelial Cell ◽  
Lung Development ◽  
Fetal Lung ◽  
Normal Lung ◽  
Mrna Levels ◽  
Lung Growth ◽  
Fetal Sheep ◽  
Lung Expansion

The degree of fetal lung expansion is a critical determinant of fetal lung growth and alveolar epithelial cell (AEC) differentiation, although the mechanisms involved are unknown. As VDUP1 (vitamin D3-upregulated protein 1) can modulate cell proliferation, can induce cell differentiation, and is highly expressed in the lung, we have investigated the effects of fetal lung expansion on VDUP1 expression and its relationship to expansion-induced fetal lung growth and AEC differentiation in fetal sheep. Alterations in fetal lung expansion caused profound changes in VDUP1 mRNA levels in lung tissue. Increased fetal lung expansion significantly reduced VDUP1 mRNA levels from 100 ± 8% in control fetuses to 37 ± 4, 46 ± 4, and 45 ± 9% of control values at 2, 4, and 10 days of increased fetal lung expansion, respectively. Reduced fetal lung expansion increased VDUP1 mRNA levels from 100 ± 16% in control fetuses to 162 ± 16% of control values after 7 days. VDUP1 was localized to airway epithelium in small bronchioles, AECs, and some mesenchymal cells. Its expression was inversely correlated with cell proliferation during normal lung development ( R2 = 0.972, P < 0.002) as well as in response to alterations in fetal lung expansion ( R2 = 0.956, P < 0.001) and was positively correlated with SP-B expression during normal lung development ( R2 = 0.803, P < 0.0001) and following altered lung expansion ( R2 = 0.817, P < 0.001). We suggest that VDUP1 may be an important mediator of expansion-induced lung cell proliferation and AEC differentiation in the developing lung.

Regulation of alveolar epithelial cell ICAM-1 expression by cell shape and cell-cell interactions

1994 ◽  
Vol 266 (4) ◽  
pp. L476-L484 ◽  
Author(s):  
R. Paine ◽  
P. Christensen ◽  
G. B. Toews ◽  
R. H. Simon
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Basement Membrane ◽  
Adhesion Molecule ◽  
Alveolar Epithelial Cell ◽  
Type I ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Epithelial ◽  
Cell Expression

In normal lung, intercellular adhesion molecule 1 (ICAM-1) is expressed at high levels on thin type I alveolar epithelial cells, but is minimally expressed on cuboidal type II cells. ICAM-1 is induced in primary culture on tissue culture-treated plastic as type II cells undergo transition toward a type I cell-like phenotype. We hypothesized that alveolar epithelial cell expression of ICAM-1 might be regulated in part by signals that influence the state of differentiation of these cells. We found that rat type II cells that were cultured as aggregates of cuboidal cells on a hydrated basement membrane gel (Matrigel) or on floating type I collagen gels, expressed markedly less ICAM-1 protein and mRNA compared with cells that had spread on plastic. In contrast, type II cells that had spread as monolayers on dishes coated with basement membrane proteins in planar configuration demonstrated ICAM-1 expression comparable to that of cells on plastic alone. Thus regulation of alveolar epithelial cell expression of this immunologically important adhesion molecule involves complex spatial interactions of the cells with the basement membrane and other epithelial cells.

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