Biomedical subjects

R F Ertl

Publications and source records attributed to R F Ertl.

At least 19 recordsLinked to original sources

PubMed2001

Fibroblasts and monocyte macrophages contract and degrade three-dimensional collagen gels in extended co-culture.

BACKGROUND: Inflammatory cells are believed to play a prominent role during tissue repair and remodeling. Since repair processes develop and mature over extended time frames, the present study was designed to evaluate the effect of monocytes and fibroblasts in prolonged culture in three-dimensional collagen gels. METHODS: Blood monocytes from healthy donors and human fetal lung fibroblasts were cast into type I collagen gels and maintained in floating cultures for three weeks. RESULTS: Fibroblast-mediated gel contraction was initially inhibited by the presence of monocytes (P < 0.01). However, with extended co-culture, contraction of the collagen gels was greatly augmented (P < 0.01). In addition, with extended co-culture, degradation of collagen in the gels occurred. The addition of neutrophil elastase to the medium augmented both contraction and degradation (P < 0.01). Prostaglandin E2 production was significantly increased by co-culture and its presence attenuated collagen degradation. CONCLUSION: The current study, therefore, demonstrates that interaction between monocytes and fibroblasts can contract and degrade extracellular matrix in extended culture.

Cell Line↗

PubMed2001

Collaborative interactions between neutrophil elastase and metalloproteinases in extracellular matrix degradation in three-dimensional collagen gels.

BACKGROUND: Extended culture of monocytes and fibroblasts in three-dimensional collagen gels leads to degradation of the gels (see linked study in this issue, "Fibroblasts and monocytes contract and degrade three-dimensional collagen gels in extended co-culture"). The current study, therefore, was designed to evaluate production of matrix-degrading metalloproteinases by these cells in co-culture and to determine if neutrophil elastase could collaborate in the activation of these enzymes. Since co-cultures produce prostaglandin E2 (PGE2), the role of PGE2 in this process was also evaluated. METHODS: Blood monocytes from healthy donors and human fetal lung fibroblasts were cast into type I collagen gels and maintained in floating cultures for three weeks. Matrix metalloproteinases (MMPs) were assessed by gelatin zymography (MMPs 2 and 9) and immunoblotting (MMPs 1 and 3). The role of PGE2 was explored by direct quantification, and by the addition of exogenous indomethacin and/or PGE2. RESULTS: Gelatin zymography and immunoblots revealed that MMPs 1, 2, 3 and 9 were induced by co-cultures of fibroblasts and monocytes. Neutrophil elastase added to the medium resulted in marked conversion of latent MMPs to lower molecular weight forms consistent with active MMPs, and was associated with augmentation of both contraction and degradation (P < 0.01). PGE2 appeared to decrease both MMP production and activation. CONCLUSION: The current study demonstrates that interactions between monocytes and fibroblasts can mediate tissue remodeling.

Blotting, Western↗

PubMed2001

Glucocorticoids and TGF-beta1 synergize in augmenting fibroblast mediated contraction of collagen gels.

TGF-beta plays a central role in the initiation and progression of pulmonary fibrosis. Glucocorticoids are frequently used to treat fibrotic diseases, but beneficial effects are often modest. Both TGF-beta and glucocorticoids have been reported to increase fibroblast contraction of native collagen gels, a model of fibrotic tissue remodeling. Therefore, we sought to determine how glucocorticoids interact with TGF-beta in this system. In this study, human fetal lung fibroblasts (HFL-1) were pretreated with or without TGF-beta for 72 h before they were cast into type I collagen gels. Various concentrations of glucocorticoids (budesonide or hydrocortisone) were added at the time of casting. Gel size was then monitored at different times after gel release. The surrounding media were collected for the assay of prostaglandin E2 (PGE2) and the cell lysates were analyzed for cyclooxygenase (COX) expression by immunoblot. Glucocorticoids alone significantly enhanced fibroblast-mediated contraction of collagen gels (P < 0.01) and dose-dependently inhibited PGE2 release by HFL-1 fibroblasts. TGF-beta significantly augmented gel contraction but also induced a 30% increase in PGE2 release and increased the expression of COX-1. Glucocorticoids inhibited TGF-beta1 induced-PGE2 release, and enhanced TGF-beta augmented gel contraction without significantly affecting TGF-beta augmented COX-1 expression. Indomethacin, a COX inhibitor, increased TGF-beta augmented gel contraction but had no further effect when added together with glucocorticoids. Thus, glucocorticoids can synergize with TGF-beta in augmenting fibroblast mediated collagen gel contraction through the inhibition of PGE2 production. Such interactions between glucocorticoids and TGF-beta may account, in part, for the lack of response of fibrotic diseases to glucocorticoids.

Budesonide↗

PubMed2001

Synergistic neutrophil elastase-cytokine interaction degrades collagen in three-dimensional culture.

Proteolytic degradation of extracellular matrix is thought to play an important role in many lung disorders. In the current study, human lung fibroblasts were cast into type I collagen gels and floated in medium containing elastase, cytomix (combination of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma), or both. After 5 days, gel collagen content was determined by measuring hydroxyproline. Elastase alone did not result in collagen degradation, but in the presence of fibroblasts, elastase reduced hydroxyproline content to 75.2% (P < 0.01), whereas cytomix alone resulted in reduction of hydroxyproline content to 93% (P < 0.05). The combination of elastase and cytomix reduced hydroxyproline content to 5.2% (P < 0.01). alpha(1)-Proteinase inhibitor blocked this synergy. Gelatin zymography and Western blot revealed that matrix metalloproteinase (MMP)-1, -3, and -9 were induced by cytomix and activated in the presence of elastase. Tissue inhibitor of metalloproteinase (TIMP)-1 and -2 were also induced by cytomix but were cleaved by elastase. We conclude that a synergistic interaction between cytomix and elastase, mediated through cytokine induction of MMP production and elastase-induced activation of latent MMPs and degradation of TIMPs, can result in a dramatic augmentation of collagen degradation. These findings support the notion that interaction among inflammatory mediators secreted by mononuclear cells and neutrophils can induce tissue cells to degrade extracellular matrix. Such a mechanism may contribute to the protease-anti-protease imbalance in emphysema.

Animals↗

PubMed2001

Prostaglandin E(2) inhibits fibroblast chemotaxis.

Fibroblasts are the major source of extracellular connective tissue matrix, and the recruitment, accumulation, and stimulation of these cells are thought to play important roles in both normal healing and the development of fibrosis. Prostaglandin E(2) (PGE(2)) can inhibit this process by blocking fibroblast proliferation and collagen production. The aim of this study was to investigate the inhibitory effect of PGE(2) on human plasma fibronectin (hFN)- and bovine bronchial epithelial cell-conditioned medium (BBEC-CM)-induced chemotaxis of human fetal lung fibroblasts (HFL1). Using the Boyden blind well chamber technique, PGE(2) (10(-7) M) inhibited chemotaxis to hFN 40.8 +/- 5.3% (P < 0.05) and to BBEC-CM 49.7 +/- 11.7% (P < 0.05). Checkerboard analysis demonstrated inhibition of both chemotaxis and chemokinesis. The effect of PGE(2) was concentration dependent, and the inhibitory effect diminished with time. Other agents that increased fibroblast cAMP levels, including isoproterenol (10(-5) M), dibutyryl cAMP (10(-5) M), and forskolin (3 x 10(-5) M) had similar effects and inhibited chemotaxis 54.1, 95.3, and 87.0%, respectively. The inhibitory effect of PGE(2) on HFL1 cell chemotaxis was inhibited by the cAMP-dependent protein kinase (PKA) inhibitor KT-5720, which suggests a cAMP-dependent effect mediated by PKA. In summary, PGE(2) appears to inhibit fibroblast chemotaxis, perhaps by modulating the rate of fibroblast migration. Such an effect may contribute to regulation of the wound healing response after injury.

Adrenergic beta-Agonists↗

PubMed2001

Retinoic acid attenuates cytokine-driven fibroblast degradation of extracellular matrix in three-dimensional culture.

Proteolytic degradation of extracellular matrix is thought to play an important role both in emphysema and in tissue development and repair. Retinoic acid has been suggested to modify tissue injury, and in an animal model of emphysema may induce alveolar repair. Since cytokines can induce matrix metalloproteinase (MMP) production in fibroblasts and neutrophil elastase (NE) can activate MMPs, we hypothesized that retinoic acid could attenuate collagen degradation by modifying MMP production and activation. To evaluate this, human lung fibroblasts were cast into native type I collagen gels and floated in medium containing cytomix (TNF-alpha, IL-1beta, and IFN-gamma) alone or in combination with NE in the presence and absence of retinoic acid (1 microM). After 5 d, cytomix with elastase induced significant degradation of the collagen gels assessed by quantifying total hydroxyproline (41.6 +/- 1.6 microg versus 3.3 +/- 1.5 microg, P < 0.01). Retinoic acid significantly inhibited this degradation (23.3 +/- 1.5 microg versus 3.3 +/- 1.5 microg, P < 0.01). Gelatin zymography and Western blot revealed that MMP-1, MMP-3, and MMP-9 were induced by cytomix and that co-exposure to NE resulted in increased production of activated forms of these enzymes. Retinoic acid attenuated the induction and activation of MMP-1 and MMP-3. The current study, therefore, suggests that in addition to stimulating anabolic effects, retinoic acid may modulate proteolytic processes thought to contribute to tissue destruction in emphysema.

Animals↗

PubMed2000

Blood monocytes attenuate lung fibroblast contraction of three-dimensional collagen gels in coculture.

Mononuclear phagocytes can interact with mesenchymal cells and extracellular matrix components that are crucial for connective tissue rearrangement. We asked whether blood monocytes can alter matrix remodeling mediated by human lung fibroblasts cultured in a three-dimensional collagen gel. Blood monocytes from healthy donors (>95% pure) were cast into type I collagen gels that contained lung fibroblasts. Monocytes in coculture inhibited the fibroblast-mediated gel contractility in a time- and concentration-dependent manner. The concentration of PGE(2), a well-known inhibitor of gel contraction, was higher (P < 0.01) in media from coculture; this media attenuated fibroblast gel contraction, whereas conditioned media from either cell type cultured alone did not. Three-dimensional cultured monocytes responded to conditioned media from cocultures by producing interleukin-1beta and tumor necrosis factor-alpha, whereas fibroblasts increased synthesis of PGE(2). Antibodies to interleukin-1beta and tumor necrosis factor-alpha blocked the monocyte inhibitory effect and reduced the amount of PGE(2) produced. The ability of monocytes to block the fibroblast contraction of matrix may be an important mechanism in regulating tissue remodeling.

Cell Culture Techniques↗

PubMed2000

Chicken soup inhibits neutrophil chemotaxis in vitro.

Chicken soup has long been regarded as a remedy for symptomatic upper respiratory tract infections. As it is likely that the clinical similarity of the diverse infectious processes that can result in "colds" is due to a shared inflammatory response, an effect of chicken soup in mitigating inflammation could account for its attested benefits. To evaluate this, a traditional chicken soup was tested for its ability to inhibit neutrophil migration using the standard Boyden blindwell chemotaxis chamber assay with zymosan-activated serum and fMet-Leu-Phe as chemoattractants. Chicken soup significantly inhibited neutrophil migration and did so in a concentration-dependent manner. The activity was present in a nonparticulate component of the chicken soup. All of the vegetables present in the soup and the chicken individually had inhibitory activity, although only the chicken lacked cytotoxic activity. Interestingly, the complete soup also lacked cytotoxic activity. Commercial soups varied greatly in their inhibitory activity. The present study, therefore, suggests that chicken soup may contain a number of substances with beneficial medicinal activity. A mild anti-inflammatory effect could be one mechanism by which the soup could result in the mitigation of symptomatic upper respiratory tract infections.

Animals↗

PubMed1999

Modulation of elastase binding to elastin by human alveolar macrophage-derived lipids.

Human neutrophil elastase (HNE), an enzyme secreted by activated neutrophils, can bind to and degrade extracellular matrix including human lung elastin. This protease is believed to play an important role in several destructive processes including pulmonary emphysema. In this study, we hypothesized that an alveolar macrophage (AM) product or products may interact with neutrophil elastase (NE) and modulate its binding to elastin. Elastase binding to elastase was evaluated by a modified elastase functional assay using a synthetic substrate. Supernatants from cultured AM inhibited elastase binding to elastin at a dose-dependent manner without inhibiting functional elastase activity. The AM products had a heterogeneous molecular weight ranging from 440,000 to 54,000. The activity was heat-stable, but was lost after ultracentrifugation. After lipid fractionation, neither the aqueous nor the lipid fractions contained activity, suggesting that the factor may be a lipid complex. Culture supernatants from smokers' AM released significantly higher amounts of the factor than nonsmokers. In addition, high-molecular-weight elastase was present in bronchoalveolar lavage fluid (BALF) obtained from patients with pneumonia. Most of the in vivo high-molecular-weight elastase was lost after lipid extraction. In conclusion, macrophages release a factor or factors, probably lipid, which can interact with NE and inhibit its binding to human lung elastin without inhibiting elastase activity. This macrophage-derived factor may play a role in protecting the lung from NE by partitioning elastase into the airspace and thus protecting the interstitial connective tissue matrix from elastase degradation.

Adult↗

PubMed1997

Selective migration of alpha-smooth muscle actin-positive myofibroblasts toward fibronectin in the Boyden's blindwell chamber.

1. In order to address the hypothesis that migrating fibroblasts have a different phenotype, human fetal lung fibroblasts (HFL-1) cells were evaluated in the Boyden blindwell chamber migration assay followed by immunoelectron microscopy. 2. HFL-1 cells were placed on nucleopore filters and incubated for 2 h using purified human plasma fibronectin (pFn) as a chemoattractant. Filters were then processed for immunoelectron microscopy using antibodies for alpha-smooth muscle (alpha-SM) actin as a marker for myofibroblasts, cellular fibronectin (cFn) and VLA-5. 3. Cells which had migrated to the bottom side of the filter were more likely to express alpha-SM actin, 29.1 +/- 3.4% of cells, compared with cells which did not migrate through the filter, 12.4 +/- 1.3% (P < 0.05). The total proportion of alpha-SM-actin-positive cells located on both sides of the filter showed no difference between those which had migrated toward pFn and controls (17.7 +/- 1.0% compared with 20.2 +/- 2.5%). 4. cFn-positive cells showed minimal differences compared with control cells, while perinuclear and endoplasmic reticulum staining of VLA-5 was observed only in the cells treated with pFn. 5. The results show that HFL-1 cells are heterogenous for alpha-SM actin expression. Short-term incubation with pFn did not change the proportion of alpha-SM-actin-positive HFL-1 cells. Cells which migrate, however, are enriched for alpha-SM actin expression. pFn-induced fibroblast chemotaxis can selectively recruit myofibroblasts with increased alpha-SM actin expression, a feature which may contribute to the altered population of cells at sites of fibrosis.

Actins↗

PubMed1996

Lipopolysaccharide increases fibronectin production and release from cultured lung fibroblasts partially through proteolytic activity.

Fibronectin is a major product of fibroblasts and can mediate diverse functions including wound healing. Chronic bacterial infections are generally associated with a marked decreased in the ability to repair. We therefore hypothesized that bacterial endotoxin, lipopolysaccharide (LPS), might alter fibroblast fibronectin production. LPS augmented fibronectin production by fibroblasts and also stimulated the release of fibronectin from cell layers. An increase in new protein synthesis appeared to account for part of the increased fibronectin, because the inhibitor of protein synthesis, cycloheximide, inhibited the increase in total production of fibronectin. Cycloheximide did not attenuate the increased release of fibronectin into the culture medium. This increased release appeared to be caused, at least in part, by fragmentation of fibronectin by proteases contained in LPS preparations. In this regard all preparations of LPS tested were found to cleave fibronectin. Finally, zymograms indicated that LPS could also cleave gelatin with at least two bands of proteolytic activity but that it did not cleave bovine serum albumin or ovalbumin. These results indicate that the ability of bacterial products to alter fibronectin production and to degrade this macromolecule may account for altered wound repair that occurs with chronic bacterial infection.

Cell Line↗

PubMed1995

Cigarette smoke stimulates release of neutrophil chemotactic activity from cultured bovine bronchial epithelial cells.

1. Recruitment of neutrophils into the airway is a prominent feature of chronic bronchitis, a syndrome often associated with exposure to cigarette smoke. Since bronchial epithelial cells are the 'first' lung cells to come into contact with smoke, these cells may be responsible for neutrophil recruitment into the airway by release of neutrophil chemotactic activity in response to cigarette smoke. 2. To evaluate this hypothesis, we prepared bovine bronchial epithelial cells and measured their ability to release neutrophil chemotactic activity following exposure to cigarette smoke. Bronchial epithelial cells were prepared by overnight digestion with protease, filtered through 100-microns Nitex mesh and resuspended in Dulbecco's modified Eagle medium supplemented with 10% fetal calf serum and antibiotics and cultured at 2 x 10(6) cells in 2 ml of medium in 35-mm culture dishes. After 4 days, dishes were rinsed and refed with medium without fetal calf serum and incubated with and without 1:10 diluted smoke extract for 6 h at 37 degrees C. The neutrophil chemotactic activity of the supernatant fluids was measured by the blindwell chamber technique. 3. Cigarette smoke itself added to medium did not stimulate chemotaxis. In contrast, cigarette smoke did stimulate the release of neutrophil chemotactic activity from bovine bronchial epithelial cells [15 +/- 3 (control) versus 74 +/- 5 (smoke), P < 0.01]. 4. This neutrophil chemotactic activity was dialysable, pepsin and acid stable, heat sensitive and lipid extractable. Sephadex G-75 column chromatography demonstrated two peaks of neutrophil chemotactic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Bronchial epithelial cells regulate fibroblast proliferation.

Chronic bronchitis frequently leads to irreversible airway obstruction. Alteration of airway architecture with abnormal airway connective tissue is thought to play an important role in this process. We hypothesized that the epithelial cells that line the airways modulate the development of peribronchial fibrosis and fixed airway obstruction by directing fibroblast proliferation. To assess this, we examined stimulatory activities for human lung fibroblast proliferation in bovine bronchial epithelial cell-conditioned medium. The conditioned medium stimulated the proliferation of fibroblasts in a serum-free culture system in a concentration-dependent manner. The fibroblast growth stimulatory activity was heterogenous, with molecular masses of > 50 and approximately 10 kDa. Bronchial epithelial cell-conditioned medium also contained fibroblast growth inhibitory factors, including both transforming growth factor (TGF)-beta and, based on indomethacin sensitivity, cyclooxygenase products. TGF-beta appeared to contribute to the morphological change of fibroblasts induced by the conditioned medium. Co-culture of human lung fibroblasts with bronchial epithelial cells resulted in a stimulation of fibroblast proliferation. In summary, airway epithelial cells appear to regulate fibroblast proliferation and may play a role in peribronchial fibrosis in chronic bronchitis.

Animals↗

PubMed1995

Cigarette smoke inhibits lung fibroblast proliferation and chemotaxis.

Cigarette smoking is the most clearly recognized cause of pulmonary emphysema. Since loss of lung tissue, which characterizes emphysema, represents a balance between injury and repair, we hypothesized that cigarette smoke might contribute to the development of emphysema by inhibiting fibroblast proliferation and migration. To evaluate this, we examined the effect of cigarette smoke extract (CSE) on the proliferation and migration of human lung fibroblasts in vitro. CSE inhibited fibroblast proliferation and migration at noncytotoxic concentrations. When CSE was treated to remove volatile components, it showed less inhibitory activity on fibroblast proliferation. Therefore, we also examined acrolein and acetaldehyde, which are volatile components of cigarette smoke, Micromolar concentrations of acrolein and millimolar concentrations of acetaldehyde induced significant inhibition of fibroblast proliferation. In contrast, removal of volatile components did not eliminate the inhibitory activity of CSE for fibroblast migration, although acetaldehyde and acrolein alone were also capable of inhibiting chemotaxis. Cigarette smoke-induced inhibition of fibroblast proliferation and migration may impair lung repair following lung injury, and may thus contribute to the development of pulmonary emphysema.

Acetaldehyde↗

PubMed1995

Modulation of fibroblast type I collagen and fibronectin production by bovine bronchial epithelial cells.

To elucidate bronchial epithelial cell (BEC)-fibroblast interactions with regard to extracellular matrix production, bovine BECs were cultured, and conditioned media were assayed for their effects on fibroblast extracellular matrix production. Bovine BECs were prepared by protease digestion and grown in serum-free medium. When confluent, 48-h conditioned medium (CM) was collected and added to confluent human fetal lung fibroblasts (HFL-1) with 10 micrograms/ml ascorbic acid every other day. Type I collagen and fibronectin production from fibroblasts were quantified by enzyme-linked immunosorbent assay. Fifty percent BEC CM caused an increase in type I collagen (582 +/- 92 pg/10(3) cells/h versus 220 +/- 42, P < 0.001) and in fibronectin (1,422 +/- 60 pg/10(3) cells/h versus 360 +/- 24, P < 0.001) production after 4 days. These observations were confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography in HFL-1 cultures labeled with [14C]proline. Dose-dependent stimulation was observed in response to BEC CM. Stimulation of macromolecule release was accompanied by increased steady-state fibronectin and alpha 1 (I) collagen mRNA levels. Sephadex G-150 column chromatography of BEC CM revealed two distinct peaks of activity at approximate molecular weights of 25 kD and > 66 kD. Transforming growth factor beta (TGF-beta)-neutralizing antibody blocked the activity of both peaks, suggesting that TGF-beta produced by the epithelial cells may drive fibroblast matrix production and that a TGF-beta binding substance may be present, or that TGF-beta aggregation may occur. Because some partially purified preparations had increased stimulatory activity compared to crude supernatants, potential inhibitors of matrix production were also sought.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Bronchial epithelial cells release neutrophil chemotactic activity in response to tachykinins.

The purpose of this study was to determine whether substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) induce the release of neutrophil chemotactic activity (NCA) from bovine bronchial epithelial cells (BBEC) and whether neutral endopeptidase (NEP), a membrane-bound metalloenzyme that hydrolyzes tachykinins, modulates these effects. BBEC monolayers were exposed to SP, NKA, and NKB in the absence or presence of phosphoramidon (10(-6) M), a selective NEP inhibitor, for 72 h. Using a modified blind-well in vitro neutrophil chemotaxis assay, we found that tachykinin-exposed BBEC culture supernatant fluids induced significant neutrophil chemotaxis compared with supernatants obtained from unstimulated BBEC. Maximal effect was observed after 48 h of incubation and at SP concentration of 10(-13) M [92 +/- 3 (SP) vs. 64 +/- 2 (media) cells/high-power field (HPF), mean +/- SE, n = 7, P less than 0.05]. Release of NCA was mediated by the COOH-terminal of the SP molecule. The rank order of potency of tachykinins in inducing release of NCA was SP greater than NKA = NKB. SP-induced response was significantly potentiated by phosphoramidon (109 +/- 3 vs. 92 +/- 3 cells/HPF, n = 7, P less than 0.05), whereas other proteinase inhibitors had no effect. The released NCA was composed of protein and lipid-soluble components. These data indicate that mammalian tachykinins induce the release of NCA from BBEC and that NEP modulates these effects. We suggest that tachykinins regulate neutrophil recruitment into the lower respiratory tract, in part, by inducing the release of NCA from airway epithelial cells.

Animals↗

PubMed1992

Modulation of fibronectin production of bovine bronchial epithelial cells by transforming growth factor-beta.

Regulation of airway repair after injury is poorly understood but is thought to be important in the development of airway diseases such as chronic bronchitis and asthma. There is evidence that fibronectin (Fn), an extracellular matrix glycoprotein, has a role in repair processes. In addition, transforming growth factor-beta (TGF-beta) is also likely involved in would healing and is known to influence extracellular matrix constituents in other cell systems. We postulated that TGF-beta may effect airway repair by modulating Fn production from airway epithelial cells. To examine this hypothesis, we studied the effect of TGF-beta 1 on Fn production by bovine bronchial epithelial cells in culture. Fn, released into the media of cultures exposed to TGF-beta 1, increased in a dose- and time-responsive fashion. Fn in the cell layer also increased in response to TGF-beta 1. De novo protein synthesis was demonstrated by an increase in [35S]methionine incorporation into Fn immunoprecipitated from media of TGF-beta-treated cultures. TGF-beta 1 also induced an increase in expression of Fn mRNA from cultured bronchial epithelial cells, suggesting that TGF-beta modulates Fn production of these cells, at least in part, through modulation of Fn gene expression. These data support a role for TGF-beta in airway repair through modulation of Fn production by airway epithelium.

Animals↗

PubMed1991

Vitronectin in bronchoalveolar lavage fluid is increased in patients with interstitial lung disease.

Vitronectin, also known as S-protein, is a 75,000-dalton serum glycoprotein that has a variety of functions, including the capacity to interact with the terminal components of the complement cascade, the coagulation system, and cell surfaces. By virtue of its ability to interact with cells, vitronectin is capable of mediating cell-spreading and adhesion and may also influence cell differentiation and cell growth. To investigate the possibility that vitronectin might contribute to the pathogenesis of interstitial lung disease, vitronectin was measured in bronchoalveolar lavage fluid from patients with sarcoidosis, idiopathic pulmonary fibrosis, and, for comparison, normal volunteers. Vitronectin was detected in lavage fluid and serum of all study subjects. Increased lavage fluid concentrations were found in patients with interstitial lung disease when compared with normal subjects (p less than 0.005), and glucocorticoid-treated patients with interstitial lung disease had lower vitronectin levels than did untreated patients. Furthermore, on SDS-PAGE and Western blot analysis lavage fluid vitronectin comigrated with serum vitronectin, suggesting similar molecular size. Thus, vitronectin is a normal constituent of the epithelial lining fluid, and lavage fluid vitronectin is similar to serum vitronectin. The increase of vitronectin concentrations in the epithelial lining fluid of patients with interstitial lung disease suggests that vitronectin may contribute to the pathogenesis of interstitial lung disease.

Blood Proteins↗