Changes in proteoglycans and lung tissue mechanics during excessive mechanical ventilation in rats

2001 ◽  
Vol 281 (5) ◽  
pp. L1078-L1087 ◽  
Author(s):  
Rehab Al-Jamal ◽  
Mara S. Ludwig
Keyword(s):  
Extracellular Matrix ◽  
Mechanical Ventilation ◽  
Heparan Sulfate ◽  
Lung Tissue ◽  
Tissue Mechanics ◽  
Alveolar Wall ◽  
Matrix Component ◽  
Tissue Properties ◽  
Tissue Elastance

Excessive mechanical ventilation results in changes in lung tissue mechanics. We hypothesized that changes in tissue properties might be related to changes in the extracellular matrix component proteoglycans (PGs). The effect of different ventilation regimens on lung tissue mechanics and PGs was examined in an in vivo rat model. Animals were anesthetized, tracheostomized, and ventilated at a tidal volume of 8 (Vt 8), 20, or 30 (Vt 30) ml/kg, positive end-expiratory pressure of 0 (PEEP0) or 1.5 (PEEP1.5) cmH2O, and frequency of 1.5 Hz for 2 h. The constant-phase model was used to derive airway resistance, tissue elastance, and tissue damping. After physiological measurements, one lung was frozen for immunohistochemistry and the other was reserved for PG extraction and Western blotting. After 2 h of mechanical ventilation, tissue elastance and damping were significantly increased in rats ventilated at Vt 30PEEP0 compared with control rats (ventilated at Vt 8PEEP1.5). Versican, basement membrane heparan sulfate PG, and biglycan were all increased in rat lungs ventilated at Vt 30PEEP0 compared with control rats. At Vt 30PEEP0, heparan sulfate PG and versican staining became prominent in the alveolar wall and airspace; biglycan was mostly localized in the airway wall. These data demonstrate that alterations in lung tissue mechanics with excessive mechanical ventilation are accompanied by changes in all classes of extracellular matrix PG.

Airway inhomogeneities contribute to apparent lung tissue mechanics during constriction

1996 ◽  
Vol 80 (5) ◽  
pp. 1841-1849 ◽  
Author(s):  
K. R. Lutchen ◽  
Z. Hantos ◽  
F. Petak ◽  
A. Adamicza ◽  
B. Suki
Keyword(s):  
Lung Tissue ◽  
Direct Evidence ◽  
Tissue Mechanics ◽  
Tissue Properties ◽  
Tissue Resistance ◽  
Lung Resistance ◽  
Before And After ◽  
Oscillation Frequencies ◽  
G Ratio ◽  
Tissue Elastance

Recent studies have suggested that part of the measured increase in lung tissue resistance after bronchoconstriction is an artifact due to increased airway inhomogeneities. To resolve this issue, we measured lung impedance (ZL) in seven open-chest rats with the lungs equilibrated on room air and then on a mixture of neon and oxygen (NeOx). The rats were placed in a body box with the tracheal tube leading through the box wall. A broadband flow signal was delivered to the box. The signal contained seven oscillation frequencies in the 0.234- to 12.07-Hz range, which were combined to produce tidal ventilation. The ZL was measured before and after bronchoconstriction caused by infusion of methacholine (MCh). Partitioning of airway and tissue properties was achieved by fitting ZL with a model including airway resistance (Raw), airway inertance, tissue damping (G), and tissue elastance (H). We hypothesized that if the inhomogeneities were not significant, the apparent tissue properties would be independent of the resident gas, whereas Raw would scale as the ratio of viscosities. Indeed, during control conditions, the NeOx-to-air ratios for G and H were both 1.03 +/- 0.04. Also, there was a small increase in lung elastance (EL) between 0.234 and 4 Hz that was similar on air and NeOx. During MCh infusion, Raw and G increased markedly (45-65%), but the increase in H was relatively small ( < 13%). The NeOx-to-air Raw and H ratios remained the same. However, the NeOx-to-air G ratio increased to 1.19 +/- 0.07 (P < 0.01) and the increase in EL with frequency was now marked and dependent on the resident gas. These results provide direct evidence that for a healthy rat lung airway inhomogeneities do not significantly influence the lung resistance or EL vs. frequency data. However, during MCh-induced constriction, a large portion of the increase in tissue resistance and the altered frequency dependence of EL are virtual and a consequence of the augmented airway inhomogeneities.

Initial characterization of anosmin-1, a putative extracellular matrix protein synthesized by definite neuronal cell populations in the central nervous system

1996 ◽  
Vol 109 (7) ◽  
pp. 1749-1757 ◽  
Author(s):  
N. Soussi-Yanicostas ◽  
J.P. Hardelin ◽  
M.M. Arroyo-Jimenez ◽  
O. Ardouin ◽  
R. Legouis ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Extracellular Matrix ◽  
Nervous System ◽  
Cell Membrane ◽  
Heparan Sulfate ◽  
Matrix Protein ◽  
Neuronal Cell ◽  
Extracellular Matrix Protein ◽  
Cell Populations

The KAL gene is responsible for the X-chromosome linked form of Kallmann's syndrome in humans. Upon transfection of CHO cells with a human KAL cDNA, the corresponding encoded protein, KALc, was produced. This protein is N-glycosylated, secreted in the cell culture medium, and is localized at the cell surface. Several lines of evidence indicate that heparan-sulfate chains of proteoglycan(s) are involved in the binding of KALc to the cell membrane. Polyclonal and monoclonal antibodies to the purified KALc were generated. They allowed us to detect and characterize the protein encoded by the KAL gene in the chicken central nervous system at late stages of embryonic development. This protein is synthesized by definite neuronal cell populations including Purkinje cells in the cerebellum, mitral cells in the olfactory bulbs and several subpopulations in the optic tectum and the striatum. The protein, with an approximate molecular mass of 100 kDa, was named anosmin-1 in reference to the deficiency of the sense of smell which characterizes the human disease. Anosmin-1 is likely to be an extracellular matrix component. Since heparin treatment of cell membrane fractions from cerebellum and tectum resulted in the release of the protein, we suggest that one or several heparan-sulfate proteoglycans are involved in the binding of anosmin-1 to the membranes in vivo.

scholarly journals Heparin and heparan sulfate increase the radius of diffusion and action of basic fibroblast growth factor.

1990 ◽  
Vol 111 (4) ◽  
pp. 1651-1659 ◽  
Author(s):  
R Flaumenhaft ◽  
D Moscatelli ◽  
D B Rifkin
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Heparan Sulfate ◽  
Fibroblast Growth Factor ◽  
Morphological Changes ◽  
Fibroblast Growth ◽  
Soluble Phase ◽  
Heparan Sulfates ◽  
Sulfate Complexes

The radius of diffusion of basic FGF (bFGF) in the presence and in the absence of the glycosaminoglycans heparin and heparan sulfate was measured. Iodinated 125I-bFGF diffuses further in agarose, fibrin, and on a monolayer of bovine aortic endothelial (BAE) cells in the presence of heparin than in its absence. Heparan sulfates affected the diffusion of 125I-bFGF in a manner similar to, though less pronounced than, heparin. When applied at the center of a monolayer of BAE cells, bFGF plus heparin stimulated morphological changes at a 10-fold greater radius than bFGF alone. These results suggest that bFGF-heparin and/or heparan sulfate complexes may be more effective than bFGF alone in stimulating cells located away from the bFGF source because the bFGF-glycosaminoglycan complex partitions into the soluble phase rather than binding to insoluble glycosaminoglycans in the extracellular matrix. Thus, the complex of bFGF and glycosaminoglycan may represent one of the active forms of bFGF in vivo.

scholarly journals Effects of chronic l-NAME treatment lung tissue mechanics, eosinophilic and extracellular matrix responses induced by chronic pulmonary inflammation

2008 ◽  
Vol 294 (6) ◽  
pp. L1197-L1205 ◽  
Author(s):  
Patrícia Angeli ◽  
Carla M. Prado ◽  
Débora G. Xisto ◽  
Pedro L. Silva ◽  
Caroline P. Pássaro ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Lung Tissue ◽  
Pulmonary Inflammation ◽  
Elastic Fiber ◽  
Tissue Mechanics ◽  
Elastic Fibers ◽  
Distal Lung ◽  
Alveolar Septa

The importance of lung tissue in asthma pathophysiology has been recently recognized. Although nitric oxide mediates smooth muscle tonus control in airways, its effects on lung tissue responsiveness have not been investigated previously. We hypothesized that chronic nitric oxide synthase (NOS) inhibition by Nω-nitro-l-arginine methyl ester (l-NAME) may modulate lung tissue mechanics and eosinophil and extracellular matrix remodeling in guinea pigs with chronic pulmonary inflammation. Animals were submitted to seven saline or ovalbumin exposures with increasing doses (1∼5 mg/ml for 4 wk) and treated or not with l-NAME in drinking water. After the seventh inhalation (72 h), animals were anesthetized and exsanguinated, and oscillatory mechanics of lung tissue strips were performed in baseline condition and after ovalbumin challenge (0.1%). Using morphometry, we assessed the density of eosinophils, neuronal NOS (nNOS)- and inducible NOS (iNOS)-positive distal lung cells, smooth muscle cells, as well as collagen and elastic fibers in lung tissue. Ovalbumin-exposed animals had an increase in baseline and maximal tissue resistance and elastance, eosinophil density, nNOS- and iNOS-positive cells, the amount of collagen and elastic fibers, and isoprostane-8-PGF2α expression in the alveolar septa compared with controls ( P < 0.05). l-NAME treatment in ovalbumin-exposed animals attenuated lung tissue mechanical responses ( P < 0.01), nNOS- and iNOS-positive cells, elastic fiber content ( P < 0.001), and isoprostane-8-PGF2α in the alveolar septa ( P < 0.001). However, this treatment did not affect the total number of eosinophils and collagen deposition. These data suggest that NO contributes to distal lung parenchyma constriction and to elastic fiber deposition in this model. One possibility may be related to the effects of NO activating the oxidative stress pathway.

scholarly journals Evidence of Swim secretion and association with extracellular matrix in the Drosophila embryo

2021 ◽  
Author(s):  
Valeria Kaltezioti ◽  
Katerina M. Vakaloglou ◽  
Aristidis S. Charonis ◽  
Christos G. Zervas
Keyword(s):  
Extracellular Matrix ◽  
Expression System ◽  
Ectopic Expression ◽  
Basement Membranes ◽  
Confocal Imaging ◽  
Drosophila Embryo ◽  
Dependent Manner ◽  
Extracellular Matrix Component ◽  
Matrix Component

Secreted wingless-interacting protein (Swim) is the Drosophila ortholog gene of the mammalian Tubulointerstitial Nephritis Antigen Like 1 (TINAGL1), known also as lipocalin-7 (LCN7), or adrenocortical zonation factor 1 (AZ-1). Swim and TINAGL1 proteins share a significant homology, including the somatomedin B and the predictive inactive C1 cysteine peptidase domains. In mammals, both TINAGL1 and its closely related homolog TINAG have been identified in basement membranes, where they may function as modulators of integrin-mediated adhesion. In Drosophila, Swim was initially identified in the eggshell matrix and subsequently was detected in the culture medium of S2 cells. Further biochemical analysis indicated that Swim binds to wingless (wg) in a lipid-dependent manner. This observation together with RNAiknockdown studies suggested that Swim is an essential cofactor of wg-signalling. However, recent elegant genetic studies ruled out the possibility that Swim is required alone to facilitate wgsignalling in Drosophila, because flies without Swim are viable and fertile. Here, we use the UAS/Gal4 expression system together with confocal imaging to analyze the in vivo localization of a chimeric Swim-GFP in the developing Drosophila embryo. Our data fully support the notion that Swim is an extracellular matrix component that upon ectopic expression is secreted and preferentially associates with the basement membranes of various organs and with the specialized tendon matrix at the muscle attachment sites (MAS). Interestingly, the accumulation of Swim at the MAS does not require integrins. In conclusion, Swim is an extracellular matrix component, and it is possible that Swim exhibits overlapping functions in concert with other undefined components.

scholarly journals Localization of anticoagulantly active heparan sulfate proteoglycans in vascular endothelium: antithrombin binding on cultured endothelial cells and perfused rat aorta.

1990 ◽  
Vol 111 (3) ◽  
pp. 1293-1304 ◽  
Author(s):  
A I de Agostini ◽  
S C Watkins ◽  
H S Slayter ◽  
H Youssoufian ◽  
R D Rosenberg
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Protease Inhibitor ◽  
Heparan Sulfate ◽  
Binding Sites ◽  
Rat Aorta ◽  
Linear Increase ◽  
Heparan Sulfate Proteoglycans ◽  
Vasa Vasorum

We have studied the interaction of 125I-antithrombin (125I-AT) with microvascular endothelial cells (RFPEC) to localize the cellular site of anticoagulantly active heparan sulfate proteoglycans (HSPG). The radiolabeled protease inhibitor bound specifically to the above HSPG with a Kd of approximately 50 nM. Confluent monolayer RFPEC cultures exhibited a linear increase in the amount of AT bound per cell for up to 16 d, whereas suspension RFPEC cultures possessed a constant number of protease inhibitor binding sites per cell for up to 5 d. These results suggest that monolayer RFPEC cultures secrete anticoagulantly active HSPG, which then accumulate in the extracellular matrix. This hypothesis was confirmed by quantitative light and EM level autoradiography which demonstrated that the AT binding sites are predominantly located in the extracellular matrix with only small quantities of protease inhibitor complexed to the cell surface. We have also pinpointed the in vivo position of anticoagulantly active HSPG within the blood vessel wall. Rat aortas were perfused, in situ, with 125I-AT, and bound labeled protease inhibitor was localized by light and EM autoradiography. The anticoagulantly active HSPG were concentrated immediately beneath the aortic and vasa vasorum endothelium with only a very small extent of labeling noted on the luminal surface of the endothelial cells. Based upon the above data, we propose a model whereby luminal and abluminal anticoagulantly active HSPG regulate coagulation mechanism activity.

Lung Tissue Mechanics and Extracellular Matrix Remodeling in Acute Lung Injury

2001 ◽  
Vol 164 (6) ◽  
pp. 1067-1071 ◽  
Author(s):  
PATRICIA R. M. ROCCO ◽  
ELNARA M. NEGRI ◽  
PEDRO M. KURTZ ◽  
FERNANDA P. VASCONCELLOS ◽  
GABRIELA H. SILVA ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Tissue ◽  
Tissue Mechanics ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling
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