scholarly journals Actomyosin-based Retrograde Flow of Microtubules in the Lamella of Migrating Epithelial Cells Influences Microtubule Dynamic Instability and Turnover and Is Associated with Microtubule Breakage and Treadmilling

1997 ◽  
Vol 139 (2) ◽  
pp. 417-434 ◽  
Author(s):  
Clare M. Waterman-Storer ◽  
E.D. Salmon
Keyword(s):  
Epithelial Cells ◽  
Dynamic Instability ◽  
Leading Edge ◽  
Unknown Origin ◽  
Time Lapse ◽  
Lung Epithelial Cells ◽  
Retrograde Flow ◽  
Microtubule Dynamic ◽  
Lung Epithelial ◽  
Time Lapse Imaging

We have discovered several novel features exhibited by microtubules (MTs) in migrating newt lung epithelial cells by time-lapse imaging of fluorescently labeled, microinjected tubulin. These cells exhibit leading edge ruffling and retrograde flow in the lamella and lamellipodia. The plus ends of lamella MTs persist in growth perpendicular to the leading edge until they reach the base of the lamellipodium, where they oscillate between short phases of growth and shortening. Occasionally “pioneering” MTs grow into the lamellipodium, where microtubule bending and reorientation parallel to the leading edge is associated with retrograde flow. MTs parallel to the leading edge exhibit significantly different dynamics from MTs perpendicular to the cell edge. Both parallel MTs and photoactivated fluorescent marks on perpendicular MTs move rearward at the 0.4 μm/min rate of retrograde flow in the lamella. MT rearward transport persists when MT dynamic instability is inhibited by 100-nM nocodazole but is blocked by inhibition of actomyosin by cytochalasin D or 2,3-butanedione–2-monoxime. Rearward flow appears to cause MT buckling and breaking in the lamella. 80% of free minus ends produced by breakage are stable; the others shorten and pause, leading to MT treadmilling. Free minus ends of unknown origin also depolymerize into the field of view at the lamella. Analysis of MT dynamics at the centrosome shows that these minus ends do not arise by centrosomal ejection and that ∼80% of the MTs in the lamella are not centrosome bound. We propose that actomyosin-based retrograde flow of MTs causes MT breakage, forming quasi-stable noncentrosomal MTs whose turnover is regulated primarily at their minus ends.

Lung epithelial barrier function and wound healing are decreased by IL-4 and IL-13 and enhanced by IFN-γ

2001 ◽  
Vol 281 (6) ◽  
pp. C2029-C2038 ◽  
Author(s):  
Minoo Ahdieh ◽  
Tim Vandenbos ◽  
Adel Youakim
Keyword(s):  
Wound Healing ◽  
Epithelial Cells ◽  
Barrier Function ◽  
Leading Edge ◽  
Lung Epithelial Cells ◽  
Collagen I ◽  
Epithelial Barrier Function ◽  
Lung Epithelial ◽  
Associated Proteins ◽  
Ifn Γ

To understand the effects of cytokines on epithelial cells in asthma, we have investigated the effects of interleukin (IL)-4, IL-13, and interferon (IFN)-γ on barrier function and wound healing in Calu-3 human lung epithelial cells. IL-4 and IL-13 treatment of Calu-3 cells grown on Transwell filters resulted in a 70–75% decrease in barrier function as assessed by electrophysiological and [14C]mannitol flux measurements. In contrast, IFN-γ enhanced barrier function threefold using these same parameters. Cells treated concurrently with IFN-γ and IL-4 or IL-13 showed an initial decline in barrier function that was reversed within 2 days, resulting in barrier levels comparable to control cells. Analysis of the tight junction-associated proteins ZO-1 and occludin showed that IL-4 and IL-13 significantly reduced ZO-1 expression and modestly decreased occludin expression compared with controls. IFN-γ, quite unexpectedly given its enhancing effect on barrier function, reduced expression of ZO-1 and occludin to almost undetectable levels compared with controls. In wound-healing assays of cells grown on collagen I, IL-4 and IL-13 decreased migration, whereas IFN-γ treatment enhanced migration, compared with control cells. Addition of IFN-γ, in combination with IL-4 or IL-13, restored migration of cells to control levels. Migration differences observed between the various cytokine treatments was correlated with expression of the collagen I-binding α2β1-integrin at the leading edge of cells at the wound front; α2β1-integrin expression was decreased in IFN-γ-treated cells compared with controls, whereas it was highest in IL-4- and IL-13-treated cells. These results demonstrate that IL-4 and IL-13 diminish the capacity of Calu-3 cells to maintain barrier function and repair wounds, whereas IFN-γ promotes epithelial restitution by enhancing barrier function and wound healing.

Legionella pneumophila induced microRNA expression in human lung epithelial cells

Pneumologie ◽  
2010 ◽  
Vol 64 (S 03) ◽  
Author(s):  
B Schmeck ◽  
B Dolniak ◽  
I Pollock ◽  
C Schulz ◽  
W Bertrams ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Legionella Pneumophila ◽  
Human Lung ◽  
Microrna Expression ◽  
Lung Epithelial Cells ◽  
Lung Epithelial ◽  
Human Lung Epithelial Cells

Microscopy study on the interaction of silica nanoparticles with lung epithelial cells

Pneumologie ◽  
2013 ◽  
Vol 67 (12) ◽  
Author(s):  
H Peuschel ◽  
T Ruckelshausen ◽  
C Cavelius ◽  
A Kraegeloh
Keyword(s):  
Epithelial Cells ◽  
Silica Nanoparticles ◽  
Microscopy Study ◽  
Lung Epithelial Cells ◽  
Lung Epithelial

scholarly journals SARS-CoV-2 drives JAK1/2-dependent local complement hyperactivation

2021 ◽  
Vol 6 (58) ◽  
pp. eabg0833
Author(s):  
Bingyu Yan ◽  
Tilo Freiwald ◽  
Daniel Chauss ◽  
Luopin Wang ◽  
Erin West ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Clinical Manifestations ◽  
Lung Epithelial Cells ◽  
Complement Factor ◽  
Respiratory Epithelial Cells ◽  
Signature Genes ◽  
Wide Range ◽  
Lung Epithelial ◽  
Gene Transcripts ◽  
Respiratory Epithelial

Patients with coronavirus disease 2019 (COVID-19) present a wide range of acute clinical manifestations affecting the lungs, liver, kidneys and gut. Angiotensin converting enzyme (ACE) 2, the best-characterized entry receptor for the disease-causing virus SARS-CoV-2, is highly expressed in the aforementioned tissues. However, the pathways that underlie the disease are still poorly understood. Here, we unexpectedly found that the complement system was one of the intracellular pathways most highly induced by SARS-CoV-2 infection in lung epithelial cells. Infection of respiratory epithelial cells with SARS-CoV-2 generated activated complement component C3a and could be blocked by a cell-permeable inhibitor of complement factor B (CFBi), indicating the presence of an inducible cell-intrinsic C3 convertase in respiratory epithelial cells. Within cells of the bronchoalveolar lavage of patients, distinct signatures of complement activation in myeloid, lymphoid and epithelial cells tracked with disease severity. Genes induced by SARS-CoV-2 and the drugs that could normalize these genes both implicated the interferon-JAK1/2-STAT1 signaling system and NF-κB as the main drivers of their expression. Ruxolitinib, a JAK1/2 inhibitor, normalized interferon signature genes and all complement gene transcripts induced by SARS-CoV-2 in lung epithelial cell lines, but did not affect NF-κB-regulated genes. Ruxolitinib, alone or in combination with the antiviral remdesivir, inhibited C3a protein produced by infected cells. Together, we postulate that combination therapy with JAK inhibitors and drugs that normalize NF-κB-signaling could potentially have clinical application for severe COVID-19.

scholarly journals Metformin Protects against Radiation-Induced Acute Effects by Limiting Senescence of Bronchial-Epithelial Cells

2021 ◽  
Vol 22 (13) ◽  
pp. 7064
Author(s):  
Christine Hansel ◽  
Samantha Barr ◽  
Alina V. Schemann ◽  
Kirsten Lauber ◽  
Julia Hess ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Lung Tissue ◽  
Cellular Stress ◽  
Lung Epithelial Cells ◽  
Normal Lung Tissue ◽  
Normal Lung ◽  
Metformin Treatment ◽  
Acute Effects ◽  
Lung Epithelial ◽  
Radiation Induced

Radiation-induced damage to normal lung parenchyma remains a dose-limiting factor in thorax-associated radiotherapy (RT). Severe early and late complications with lungs can increase the risk of morbidity in cancer patients after RT. Herein, senescence of lung epithelial cells following RT-induced cellular stress, or more precisely the respective altered secretory profile, the senescence-associated secretory phenotype (SASP), was suggested as a central process for the initiation and progression of pneumonitis and pulmonary fibrosis. We previously reported that abrogation of certain aspects of the secretome of senescent lung cells, in particular, signaling inhibition of the SASP-factor Ccl2/Mcp1 mediated radioprotection especially by limiting endothelial dysfunction. Here, we investigated the therapeutic potential of a combined metformin treatment to protect normal lung tissue from RT-induced senescence and associated lung injury using a preclinical mouse model of radiation-induced pneumopathy. Metformin treatment efficiently limited RT-induced senescence and SASP expression levels, thereby limiting vascular dysfunctions, namely increased vascular permeability associated with increased extravasation of circulating immune and tumor cells early after irradiation (acute effects). Complementary in vitro studies using normal lung epithelial cell lines confirmed the senescence-limiting effect of metformin following RT finally resulting in radioprotection, while fostering RT-induced cellular stress of cultured malignant epithelial cells accounting for radiosensitization. The radioprotective action of metformin for normal lung tissue without simultaneous protection or preferable radiosensitization of tumor tissue might increase tumor control probabilities and survival because higher radiation doses could be used.

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