scholarly journals Plasma membrane overgrowth causes fibrotic collagen accumulation and immune activation in Drosophila adipocytes

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Yiran Zang ◽  
Ming Wan ◽  
Min Liu ◽  
Hongmei Ke ◽  
Shuangchun Ma ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Chronic Diseases ◽  
Immune Activation ◽  
Tissue Damage ◽  
Collagen Iv ◽  
Matrix Proteins ◽  
Immune Signaling ◽  
Damage Response ◽  
Collagen Accumulation ◽  
Fibrotic Diseases

Many chronic diseases are associated with fibrotic deposition of Collagen and other matrix proteins. Little is known about the factors that determine preferential onset of fibrosis in particular tissues. Here we show that plasma membrane (PM) overgrowth causes pericellular Collagen accumulation in Drosophila adipocytes. We found that loss of Dynamin and other endocytic components causes pericellular trapping of outgoing Collagen IV due to dramatic cortex expansion when endocytic removal of PM is prevented. Deposits also form in the absence of negative Toll immune regulator Cactus, excess PM being caused in this case by increased secretion. Finally, we show that trimeric Collagen accumulation, downstream of Toll or endocytic defects, activates a tissue damage response. Our work indicates that traffic imbalances and PM topology may contribute to fibrosis. It also places fibrotic deposits both downstream and upstream of immune signaling, consistent with the chronic character of fibrotic diseases.

scholarly journals Chemokine receptor trafficking coordinates neutrophil clustering and dispersal at wounds in zebrafish

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Caroline Coombs ◽  
Antonios Georgantzoglou ◽  
Hazel A. Walker ◽  
Julian Patt ◽  
Nicole Merten ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Chemokine Receptor ◽  
Immune Cells ◽  
Tissue Damage ◽  
Chemokine Receptors ◽  
Inflammatory Responses ◽  
Receptor Trafficking ◽  
Migratory Response ◽  
Cell Behaviors ◽  
Downstream Signaling

AbstractImmune cells congregate at specific loci to fight infections during inflammatory responses, a process that must be transient and self-resolving. Cell dispersal promotes resolution, but it remains unclear how transition from clustering to dispersal is regulated. Here we show, using quantitative live imaging in zebrafish, that differential ligand-induced trafficking of chemokine receptors such as Cxcr1 and Cxcr2 orchestrates the state of neutrophil congregation at sites of tissue damage. Through receptor mutagenesis and biosensors, we show that Cxcr1 promotes clustering at wound sites, but is promptly desensitized and internalized, which prevents excess congregation. By contrast, Cxcr2 promotes bidirectional motility and is sustained at the plasma membrane. Persistent plasma membrane residence of Cxcr2 prolongs downstream signaling and is required for sustained exploratory motion conducive to dispersal. Thus, differential trafficking of two chemokine receptors allows coordination of antagonistic cell behaviors, promoting a self-resolving migratory response.

Hyperoxia increases plasminogen activator activity of cultured endothelial cells

1992 ◽  
Vol 262 (1) ◽  
pp. L21-L31 ◽  
Author(s):  
P. G. Phillips ◽  
L. Birnby ◽  
L. A. Di Bernardo ◽  
T. J. Ryan ◽  
M. F. Tsan
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Plasminogen Activator ◽  
Collagen Iv ◽  
Matrix Proteins ◽  
Time Dependent ◽  
Focal Contact ◽  
Oxygen Exposure ◽  
Endothelial Monolayers ◽  
Cell Fractions

Confluent calf pulmonary artery endothelial monolayers exposed to 95% oxygen for 1, 2, or 3 days exhibit a time-dependent increase in adherence to substratum, which closely parallels changes in actin cytoarchitecture and the distribution of focal contact proteins vinculin and talin. Oxygen exposure also resulted in elevated plasminogen activator (PA) activity in conditioned media (CM) and in cytoskeletal protein- and focal contact protein-enriched fractions, with highest levels achieved in the latter two fractions at 48 h after oxygen exposure. PAs have been shown to participate in dismantling of extracellular matrix in a number of physiological and pathological situations. Immunocytochemical studies demonstrated extensive restructuring of matrix proteins collagen IV, laminin, and fibronectin, which correlated temporally with elevated PA levels. Further, when protease-containing cell fractions were used to study degradation of isolated matrices, those obtained from hyperoxia-exposed cells were substantially more active than those from normoxia-exposed cells. Our data suggest that hyperoxia-induced production of PA (and perhaps other proteases) may be partly responsible for degradation of the extracellular matrix of endothelial cells.

scholarly journals The Haemophilus influenzae Hap Autotransporter Binds to Fibronectin, Laminin, and Collagen IV

2002 ◽  
Vol 70 (9) ◽  
pp. 4902-4907 ◽  
Author(s):  
Doran L. Fink ◽  
Bruce A. Green ◽  
Joseph W. St. Geme
Keyword(s):  
Extracellular Matrix ◽  
Respiratory Tract ◽  
Haemophilus Influenzae ◽  
Extracellular Matrix Proteins ◽  
Collagen Iv ◽  
Binding Domain ◽  
Matrix Proteins ◽  
Heparin Binding ◽  
Upper Respiratory Tract ◽  
Passenger Domain

ABSTRACT Nontypeable Haemophilus influenzae (NTHI) initiates infection by colonizing the upper respiratory tract mucosa. NTHI disease frequently occurs in the context of respiratory tract inflammation, where organisms encounter damaged epithelium and exposed basement membrane. In this study, we examined interactions between the H. influenzae Hap adhesin and selected extracellular matrix proteins. Hap is an autotransporter protein that undergoes autoproteolytic cleavage, with release of the adhesive passenger domain, Haps, from the bacterial cell surface. We found that Hap promotes bacterial adherence to purified fibronectin, laminin, and collagen IV and that Hap-mediated adherence is enhanced by inhibition of autoproteolysis. Adherence is inhibited by pretreatment of bacteria with a polyclonal antiserum recognizing Haps. Purified Haps binds with high affinity to fibronectin, laminin, and collagen IV but not to collagen II. Binding of Haps to fibronectin involves interaction with the 45-kDa gelatin-binding domain but not the 30-kDa heparin-binding domain of fibronectin. Taken together, these observations suggest that interactions between Hap and extracellular matrix proteins may play an important role in NTHI colonization of the respiratory tract.

scholarly journals Peroxidasin mediates bromination of tyrosine residues in the extracellular matrix

2020 ◽  
Vol 295 (36) ◽  
pp. 12697-12705
Author(s):  
Boushra Bathish ◽  
Martina Paumann-Page ◽  
Louise N. Paton ◽  
Anthony J. Kettle ◽  
Christine C. Winterbourn
Keyword(s):  
Extracellular Matrix ◽  
Protein Modification ◽  
Cultured Cells ◽  
Collagen Iv ◽  
Basement Membranes ◽  
Matrix Proteins ◽  
Tyrosine Residues ◽  
Stable Isotope Dilution ◽  
Decellularized Extracellular Matrix ◽  
Clinical Conditions

Peroxidasin is a heme peroxidase that oxidizes bromide to hypobromous acid (HOBr), a powerful oxidant that promotes the formation of the sulfilimine crosslink in collagen IV in basement membranes. We investigated whether HOBr released by peroxidasin leads to other oxidative modifications of proteins, particularly bromination of tyrosine residues, in peroxidasin-expressing PFHR9 cells. Using stable isotope dilution LC-MS/MS, we detected the formation of 3-bromotyrosine, a specific biomarker of HOBr-mediated protein modification. The level of 3-bromotyrosine in extracellular matrix proteins from normally cultured cells was 1.1 mmol/mol tyrosine and decreased significantly in the presence of the peroxidasin inhibitor, phloroglucinol. A negligible amount of 3-bromotyrosine was detected in peroxidasin-knockout cells. 3-Bromotyrosine formed both during cell growth in culture and in the isolated decellularized extracellular matrix when embedded peroxidasin was supplied with hydrogen peroxide and bromide. The level of 3-bromotyrosine was significantly higher in extracellular matrix than intracellular proteins, although a low amount was detected intracellularly. 3-Bromotyrosine levels increased with higher bromide concentrations and decreased in the presence of physiological concentrations of thiocyanate and urate. However, these peroxidase substrates showed moderate to minimal inhibition of collagen IV crosslinking. Our findings provide evidence that peroxidasin promotes the formation of 3-bromotyrosine in proteins. They show that HOBr produced by peroxidasin is selective for, but not limited to, the crosslinking of collagen IV. Based on our findings, the use of 3-bromotyrosine as a specific biomarker of oxidative damage by HOBr warrants further investigation in clinical conditions linked to high peroxidasin expression.

scholarly journals Signals via the Adaptor MyD88 in B Cells and DCs Make Distinct and Synergistic Contributions to Immune Activation and Tissue Damage in Lupus

Immunity ◽  
2013 ◽  
Vol 38 (3) ◽  
pp. 528-540 ◽  
Author(s):  
Lino L. Teichmann ◽  
Dominik Schenten ◽  
Ruslan Medzhitov ◽  
Michael Kashgarian ◽  
Mark J. Shlomchik
Keyword(s):  
B Cells ◽  
Immune Activation ◽  
Tissue Damage

scholarly journals Carcinoma cells misuse the host tissue damage response to invade the brain

Glia ◽  
2013 ◽  
Vol 61 (8) ◽  
pp. 1331-1346 ◽  
Author(s):  
Han‐Ning Chuang ◽  
Denise van Rossum ◽  
Dirk Sieger ◽  
Laila Siam ◽  
Florian Klemm ◽  
...  
Keyword(s):  
Tissue Damage ◽  
Host Tissue ◽  
Carcinoma Cells ◽  
Damage Response ◽  
The Brain

scholarly journals Modulation of 5′-nucleotidase activity in plasma membranes and intact cells by the extracellular matrix proteins laminin and fibronectin

1992 ◽  
Vol 282 (1) ◽  
pp. 181-188 ◽  
Author(s):  
N Olmo ◽  
J Turnay ◽  
G Risse ◽  
R Deutzmann ◽  
K von der Mark ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Plasma Membrane ◽  
Inhibitory Activity ◽  
Plasma Membranes ◽  
Extracellular Matrix Proteins ◽  
Cell Receptor ◽  
Inhibitory Effect ◽  
Matrix Proteins ◽  
Nucleotidase Activity ◽  
Intact Cells

Modulation of 5′-nucleotidase activity by the extracellular matrix proteins fibronectin, laminin and their fragments has been studied in plasma membrane preparations as well as in intact BCS-TC2 and Rugli cells. The ectoenzyme on plasma membranes is activated by laminin; fibronectin inhibits the AMPase activity on BCS-TC2 plasma membranes but no inhibitory effect is found in plasma membrane preparations from Rugli cells. These effects are dependent on the preincubation time and protein concentration. When the effect of the extracellular matrix proteins is studied on intact cells, both BCS-TC2 and Rugli cells show similar behaviour. A decrease in the enzyme activity is observed in the presence of fibronectin. The AMPase inhibitory activity is located on its 40 kDa fragment. No inhibitory activity is found in other fibronectin fragments, including the 140 kDa fragment which contains the RGDS cell-adhesion sequence. Laminin and its E1-4 and E8 fragments are able to activate the ecto-5′-nucleotidase activity of both BCS-TC2 and Rugli cells. The effect of the E1-4 fragment on intact cells is greater than that observed for the E8 fragment and uncleaved laminin. Our results suggest a bifunctional role for 5′-nucleotidase as ectoenzyme and cell receptor for extracellular matrix proteins.

scholarly journals Comprehensive Analysis of Human Cytomegalovirus- and HIV-Mediated Plasma Membrane Remodeling in Macrophages

mBio ◽  
2021 ◽  
Author(s):  
Ramona Businger ◽  
Saima Kivimäki ◽  
Stefan Simeonov ◽  
Georgios Vavouras Syrigos ◽  
Justus Pohlmann ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Human Cytomegalovirus ◽  
Comprehensive Analysis ◽  
Membrane Remodeling ◽  
Immune Signaling

The PM is a key component that viruses have to cope with. It is a barrier for infection and egress and is critically involved in antiviral immune signaling.

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