Biomedical subjects

M S Ludwig

Publications and source records attributed to M S Ludwig.

At least 19 recordsLinked to original sources

PubMed2006

Differences in proteoglycan deposition in the airways of moderate and severe asthmatics.

Excess deposition of proteoglycans (PGs) has been described in the subepithelial layer of the asthmatic airway wall. However, less is known about deposition in the airway smooth muscle (ASM) layer, and whether the pattern of deposition is altered depending upon disease severity. Endobronchial biopsies were performed in patients with severe or moderate asthma (defined using American Thoracic Society criteria) and in control subjects. Biopsies were immunostained for the PGs biglycan, lumican, versican and decorin. PG deposition was measured in the subepithelial and ASM layers, the former by calculating the area of positive staining, and the latter by determining the percentage area stained using point counting. Immunostaining for PGs was prominent in biopsies from both moderate and severe asthmatics, compared with control subjects. While there was no difference in the amount of PG in the subepithelial layer between the two asthmatic groups, the percentage area of biglycan and lumican staining in the ASM layer was significantly greater in moderate versus severe asthmatics. Differences in the deposition of proteoglycans within the airway smooth muscle layer of moderate versus severe asthmatics potentially impact on the functional behaviour of the airway smooth muscle in these two groups of patients.

Adult↗

PubMed2004

Changes in Smad expression and subcellular localization in bleomycin-induced pulmonary fibrosis.

Administration of bleomycin (BM) produces inflammation and fibrosis of the lung in humans and experimental animals. The molecular defects by which BM induces these pathological effects have not been studied in detail. We studied the expression of Smad family proteins, key molecules involved in mediating transforming growth factor (TGF)-beta signaling from the cell membrane to the nucleus, during the early and late phases of BM-induced fibrogenesis. Pulmonary fibrosis was induced in male Sprague-Dawley rats by a single intratracheal injection (1.5 units) of BM. Control rats received saline. Rats were killed at 3, 5, 7, 14, and 28 days after BM, cytosolic and nuclear proteins were extracted and isolated from lung tissues, and Smad proteins were probed with specific antibodies. In BM-exposed lung tissue, compared with control, Smad3 decreased persistently in the cytosol and increased transiently in the nucleus. There was a persistent increase in phosphorylation and nuclear accumulation of Smad2/3. Smad4 was increased transiently in both the cytosol and nucleus. A significant and progressive decrease in the expression of Smad7, the endogenous inhibitor of TGF-beta/Smad signaling, was observed after BM instillation. Collectively, our results indicate that an imbalance between agonistic Smads2-4 and antagonistic Smad7 may result in the unchecked activation of an autocrine TGF-beta loop, which contributes to the pathogenesis of BM-induced pulmonary fibrosis.

Animals↗

PubMed2004

Mechanical strain enhances proteoglycan message in fibroblasts from asthmatic subjects.

BACKGROUND: Remodelling of the asthmatic airway includes increased deposition of proteoglycan (PG) molecules. One of the stimuli driving airway remodelling may be excessive mechanical stimulation. OBJECTIVE: We hypothesized that fibroblasts from asthmatic patients would respond to excessive mechanical strain with up-regulation of message for PGs. METHODS: We obtained fibroblasts from asthmatic patients (AF) and normal volunteers (NF) using endobronchial biopsy. Cells were maintained in culture until the fifth passage and then grown on a flexible collagen-coated membrane. Using the Flexercell device, cells were then subjected to cyclic stretch at 30% amplitude at 1 Hz for 24 h. Control cells were unstrained. Total RNA was extracted from the cell layer and quantitative RT-PCR performed for decorin, lumican and versican mRNA. RESULTS: In unstrained cells, the expression of decorin mRNA was greater in AF than NF. With strain, NF showed increased expression of versican mRNA and AF showed increased expression of versican and decorin mRNA. The relative increase in versican mRNA expression with strain was greater in AF than NF. CONCLUSIONS: These data support the hypothesis that proteoglycan message is increased in asthmatic fibroblasts subject to mechanical strain. This finding has implications for the mechanisms governing airway wall remodelling in asthma.

Adult↗

PubMed2004

Stretch-induced changes in constricted lung parenchymal strips: role of extracellular matrix.

Large amplitude oscillations of contracted airway smooth muscle cause relative relaxation of the preparation. However, little is known about the effect of mechanical stretch on distal lung behaviour. Rat parenchymal strips were suspended in an organ bath and attached at one end to a force transducer and at the other end to a servo-controlled lever arm that effected length changes. Mechanical impedance of the strip was measured by applying a complex signal consisting of pseudorandom length oscillations of varying frequencies (0.5-19.75 Hz). A constant phase model was fit to changes in length and tension to calculate tissue damping (G) and elastance (H). Hysteresivity was calculated as G/H. Impedance was measured before and after sinusoidal length oscillation at different amplitudes (1, 3, 10 and 25% of resting length) at a frequency of 1 Hz under baseline conditions and after acetylcholine-induced constriction. Oscillations of 10 and 25% amplitudes significantly decreased the G and H of the lung strip. The effect of length oscillations was no different in control versus constricted strips. These data suggest that in the distal lung, large stretches affect the structural components of the extracellular matrix rather than the contractile elements.

Acetylcholine↗

PubMed2001

Cancer prevention and the contribution of cancer registries.

"Because they know what they do" should be the contribution of cancer registration to prevention. The public should be informed about the successes and failures of prevention. In addition, each doctor and each hospital should know the long-term results for its patients despite the complex interdisciplinary health care provision. At the same time, the regional results should be available and contrasted with clinical studies and international standards. An important criterion is also the quality of life of the patients, whose cooperation is more than overdue. According to the possibilities of prevention, six important levels can be differentiated. On each level the outcome should be evaluated on the basis of slightly differing criteria. Primary prevention has the largest incidence-, and thus, mortality-reduction potential, essentially caused by the giving up of smoking. However, the primary prevention of the tumor depends upon what kind of tumor it is, as primary prevention is possible to different extents. Often, secondary prevention is the earliest intervention possible, that is, the early detection of cancer in prognostically favorable stages. However, early detection only offers a chance of cure, albeit a smaller one, for some kinds of tumor. The third prevention level comprises primary care according to the state-of-the-art standards, followed by posttreatment care (disease-free phase) even when the disease is running a fatal course (palliative phase). In the terminal phase, adequate tumor-pain therapy and symptom-oriented measures stand for the sixth prevention level. Even the quality of life of the dying can be optimized. At the beginning of treatment at the latest, the quality of life should also be added to the outcome criteria. In this paper, the individual levels of prevention and possible evaluation criteria for successful prevention, which a modern cancer registration should submit, are discussed and examples given. If the evaluation of the quality of treatment and its significance for health care provision becomes the central tasks of the cancer registers, they will need to be transformed into service centers for hospitals, doctors, and patients.

Aftercare↗

PubMed2001

Effect of glycosaminoglycan degradation on lung tissue viscoelasticity.

We tested the hypothesis that matrix glycosaminoglycans contribute to lung tissue viscoelasticity. We exposed lung parenchymal strips to specific degradative enzymes (chondroitinase ABC, heparitinase I, and hyaluronidase) and determined whether the mechanical properties of the tissue were affected. Subpleural parenchymal strips were obtained from Sprague-Dawley rats and suspended in a Krebs-filled organ bath. One end of the strip was attached to a force transducer and the other to a servo-controlled lever arm that effected sinusoidal oscillations. Recordings of tension and length at different amplitudes and frequencies of oscillation were recorded before and after enzyme exposure. Resistance, dynamic elastance, and hysteresivity were estimated by fitting the equation of motion to changes in tension and length. Quasi-static stress-strain curves were also obtained. Exposure to chondroitinase and heparitinase I caused significant increases in hysteresivity, no decrement in resistance, and similar decreases in dynamic elastance relative to control strips exposed to Krebs solution only. Conversely, measures of static elastance were different in treated versus control strips. Hyaluronidase treatment did not alter any of the mechanical measures. These data demonstrate that digestion of chondroitin sulfate and heparan sulfate alters the mechanical behavior of lung parenchymal tissues.

Animals↗

PubMed2001

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

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 (PEEP(0)) or 1.5 (PEEP(1.5)) cmH(2)O, 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(30)PEEP(0) compared with control rats (ventilated at VT(8)PEEP(1.5)). Versican, basement membrane heparan sulfate PG, and biglycan were all increased in rat lungs ventilated at VT(30)PEEP(0) compared with control rats. At VT(30)PEEP(0), 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 Resistance↗

PubMed2001

Maturational changes in extracellular matrix and lung tissue mechanics.

The viscoelastic properties of the pulmonary parenchyma change rapidly postparturition. We compared changes in mechanical properties with changes in tissue composition of rat lung parenchymal strips in three groups of Sprague-Dawley rats: baby (B; 10-14 days), young (Y; approximately 3 wk), and adult (A; approximately 8 wk). Strips were suspended in an organ bath, and resistance (R), elastance (E), and hysteresivity (eta) were calculated during sinusoidal oscillations before and after the addition of acetylcholine (ACh) (10(-3) M). Strips were then fixed in formalin, and sections were stained with hematoxylin and eosin, Verhoff's elastic stain, or Van Gieson's picric acid-fuchsin stain for collagen. The volume proportion of collagen (%Col), the length density of elastic fibers (L(V)/Pr(alv)), and the arithmetic mean thickness of alveolar septae (T(a)) were calculated by morphometry. Tissue was also stained for alpha-smooth muscle actin (ASMA), and the volume proportion of ASMA (%ASMA) was calculated. Hyaluronic acid (HA) was quantitated by radioimmunoassay in separate strips. R and E in B strips were significantly higher, whereas eta was significantly smaller than in Y or A strips. Changes in these parameters with ACh were greater in B strips. T(a), %ASMA, and HA were greatest in B strips, whereas %Col and L(V)/Pr(alv) were least. There were significant positive correlations between R and E vs. T(a) and between percent change in R and eta post-ACh vs. T(a) and vs. %ASMA, and significant negative correlations between R and E vs. %Col and vs. L(V)/Pr(alv) and percent increase in all three mechanical parameters post-ACh vs. %Col. These data suggest that the relatively high stiffness, R, and contractile responsiveness of parenchymal tissues observed in newborns are not directly attributable to the amount of collagen and elastic fibers in the tissue, but rather they are related to the thickened alveolar wall and the relatively greater percent of contractile cells.

Acetylcholine↗

PubMed2000

Alterations in large and small proteoglycans in bleomycin-induced pulmonary fibrosis in rats.

In bleomycin (BM)-induced lung fibrosis, alterations have been shown in the expression and deposition of small proteoglycans (PGs). Less, however, is known about changes in large PGs. We investigated changes in large aggregating (versican [VS]), basement membrane (heparan sulfate proteoglycan [HSPG]), and small (biglycan and fibromodulin) PGs during the development of BM-induced pulmonary fibrosis. BM (1.5 U) was instilled intratracheally into male Sprague-Dawley rats. Control rats received saline. At 7, 14, and 28 d after administration of BM, lungs were excised; one lung was fixed in formalin and 5-microm sections were cut and stained with hematoxylin-eosin. The other lung was used for PG extraction. PGs were extracted with guanidine and were separated through composite gel polyacrylamide gel electrophoresis (PAGE) (large PGs) and sodium dodecylsulfate-PAGE (small PGs). Gels were either stained or electrophoretically transferred and probed with antibodies to VS, HSPG, biglycan, and fibromodulin. Histologic samples showed prominent inflammation, with abundant proteinaceous material, most evident in the samples obtained at 7 and 14 d after administration of BM. By 28 d after BM, much of the inflammatory response had resolved, and heterogeneous distribution of fibrosis was observed. Immunoblots showed a relative abundance of VS at 7 and 14 d. Control lungs stained minimally for VS. Levels of HSPG, biglycan, and fibromodulin were increased maximally at 14 d after administration of BM. Immunocytochemistry showed intense immunostaining of biglycan and fibromodulin in the areas of injured lung tissue from rats 14 and 28 d after BM administration. Control lungs revealed minimal staining for small PGs. Our findings indicate that changes in all subclasses of PGs occur during the development of BM-induced pulmonary fibrosis.

Animals↗

PubMed2000

Changes in extracellular matrix and tissue viscoelasticity in bleomycin-induced lung fibrosis. Temporal aspects.

Bleomycin-induced lung fibrosis results in changes in tissue mechanical properties due to alterations in the extracellular matrix (ECM). How oscillatory mechanics and changes in the matrix evolve over time has not been addressed. Sprague-Dawley rats were instilled with bleomycin sulfate (BM) (1.5 U) intratracheally; control animals (C) received saline. At 7, 14, and 28 d after BM, parenchymal strips (7 x 2 x 2 mm) were obtained and strips suspended in a Krebs-filled organ bath. One end of the strip was attached to a force (F) transducer and the other to a lever arm that effected sinusoidal length (L) oscillations. Strips were oscillated at varying amplitudes (1, 3, and 10% of resting L) and frequencies (f = 0.3, 1, 3, and 10 Hz) at an operating stress of 2 kPa. Resistance (R) and elastance (E) were estimated by fitting changes in F and L to the equation of motion. Hysteresivity (eta) was calculated as eta = (R/E) 2pif. Strips were then fixed for morphological study of collagen, elastic fibers, and the small proteoglycans (PGs), biglycan and fibromodulin (FM). R and E were significantly greater and eta significantly less in BM versus C strips (p < 0.001). The increase in R and E peaked at 14 d after BM; the decrement in eta was maximal at Day 7. Biglycan was increased in BM lung strips at all time points, FM and elastic fibers were increased at 14 and 28 d, and collagen was increased at 28 d only. Hence, changes in mechanics were maximal before collagen content had increased. In addition, we demonstrated a significant correlation between biglycan and all mechanical parameters. These data suggest that changes in PGs may be critical in determining changes in lung tissue viscoelastic behavior in this fibrosis model

Animals↗

PubMed1999

Elastic moduli of excised constricted rat lungs.

When airways constrict, the surrounding parenchyma undergoes stretch and distortion. Because of the mechanical interdependence between airways and parenchyma, the material properties of the parenchyma are important factors that modulate the degree of bronchoconstriction. The purpose of this study was to investigate the effect of changes in transpulmonary pressure (Ptp) and induced constriction on parenchymal bulk (k) and shear (mu) moduli. In excised rat lungs, pressure was measured at the airway opening, and pressure-volume curves were obtained by imposing step decreases in volume with a calibrated syringe from total lung inflation. Calculation was made of k during small-volume oscillations (1 Hz). Absolute lung volume at 0 cmH2O Ptp was obtained by saline displacement. To calculate mu, a lung-indentation test was performed. The lung surface was deformed with a cylindrical punch (diameter = 0.45 cm) in 0.25-mm increments, and the force required to effect this displacement was measured by a weight balance. Measurements of k and mu were obtained at 4 and 10 cmH2O Ptp, and again at 4 cmH2O Ptp, after delivery of methacholine aerosol (100 mg/ml) into the trachea. Values of k and mu in rat lungs were similar to those reported in other species. In addition, k and mu were dependent on Ptp. After induced constriction, k and mu increased significantly. That k and mu can increase after induced constriction has important implications vis a vis the factors modulating airway narrowing.

Aerosols↗

PubMed1999

Tidal volume amplitude affects the degree of induced bronchoconstriction in dogs.

When isolated constricted airway smooth muscle is oscillated, muscle tone decreases. We investigated whether changing tidal volume (VT) would affect induced bronchoconstriction in an in vivo canine model. Open-chest dogs were intubated with a double-lumen endotracheal tube, which isolated each main bronchus, and mechanically ventilated with a dual-cylinder ventilator. Bronchial pressure (Pbr) and flow were measured separately in each lung. Resistance and elastance were calculated by fitting the changes in Pbr, flow, and volume to the equation of motion. After baseline measurements at the same VT (150 ml), the two lungs were ventilated with different VT (50 vs. 250 ml) at a constant positive end-expiratory pressure. A continuous infusion of methacholine was begun, and measurements were repeated. The two lungs were then ventilated with the same VT (250 ml), and measurements were again repeated. A similar protocol was performed in a second group of dogs in which mean Pbr was kept constant. Bronchoconstriction was more severe in the lung ventilated with lower VT in both protocols. When VT was reset to the same amplitude in the two lungs, the difference in bronchoconstriction was abrogated. These results demonstrate that large VT inhibits airway smooth muscle contraction, regardless of mean Pbr.

Airway Resistance↗

PubMed1999

Changes in viscoelastic properties of rat lung parenchymal strips with maturation.

The lung extracellular matrix changes rapidly with maturation. To further our understanding of the mechanisms underlying lung tissue mechanics, we studied age-related changes in mechanical properties in lung parenchymal strips from baby (10-15 days old), young ( approximately 3 wk old), and adult ( approximately 8 wk old) rats. Subpleural strips were cut and suspended in a fluid-filled organ bath. One end of the strip was attached to a force transducer and the other to a servo-controlled lever arm. Measurements of force (F) and length (L) were recorded during sinusoidal oscillations of various amplitudes and frequencies. Resistance modulus (R) and elastance modulus (E) were estimated by fitting the equation of motion to changes in stress (T) and stretch ratio (lambda). Hysteresivity (eta) was calculated as follows: eta = (R/E)2pif, where f is frequency. Slow-cycling T-lambda curves were measured by applying a constant slow length change. Finally, quasi-static T-lambda curves were measured as stress was increased from 0 to 6 kPa and back to 0 kPa in stepwise increments. Our results showed that lung tissue from immature rats was stiffer and less hysteretic than tissue from more mature animals. In addition, tissue from baby animals behaved in a manner compatible with an increased vulnerability to plastic change.

Aging↗

PubMed1999

Extracellular matrix and oscillatory mechanics of rat lung parenchyma in bleomycin-induced fibrosis.

We investigated in vivo and in vitro oscillatory mechanics in bleomycin-induced fibrotic lungs and correlated these with morphometric changes in the collagen-elastin matrix and contractile cells. Fischer rats received bleomycin sulfate (BLEO,1.5 U) or saline intratracheally. Four weeks later tracheal flow and tracheal and alveolar pressure (using alveolar capsules) were measured in open-chested rats during mechanical ventilation (V T = 8 ml/kg, f = 1 Hz, PEEP = 4 cm H(2)O). Total lung, tissue, and airway resistance (R) and lung elastance (E) were calculated. In addition, excised parenchymal strips (10 x 2 x 2 mm) were studied in the organ bath. Strips were attached to a force transducer at one end and to a servo-controlled lever arm that effected length (L) changes at the other. Sinusoidal oscillations were applied (f = 1 Hz, amplitude = 2. 5% resting L and tension = 0.7 g) and R, E, and hysteresivity (eta) were calculated. Strips were then exposed to acetylcholine (ACh, 10(-)(3) M). The amount of collagen and elastic fibers in the parenchymal strip was assessed semiquantitatively by point-counting in 5-micrometer-thick sections stained with either Sirius Red or Weigert's Resorcin-fuchsin. alpha-Smooth-muscle-specific actin was detected immunohistochemically. Both in vivo and in vitro, R, E, and eta were significantly increased in BLEO rats (p < 0.05). The % increase in R, E and eta after Ach was greater in BLEO rats (p < 0. 01). There was also a significant increase in the volume proportion of collagen, elastic fibers, and actin in the parenchyma (p < 0.01). In BLEO rats, baseline R and E were correlated with the volume proportion of collagen in the parenchyma. We conclude that changes in the collagen-elastin matrix contribute to changes in the viscoelastic properties of bleomycin-treated rat lungs. Dolhnikoff M, Mauad T, Ludwig MS. Extracellular matrix and oscillatory mechanics of rat lung parenchyma in bleomycin-induced fibrosis.

Acetylcholine↗

PubMed1998

Dissociation between hysteresivity and tension in constricted tracheal and parenchymal strips.

The object of this study was to investigate how changes in the contractile state of smooth muscle would modify oscillatory mechanics of tracheal muscle and lung parenchyma during agonist challenge. Guinea pig tracheal and parenchymal lung strips were suspended in an organ bath. Measurements of length (L) and tension (T) were recorded during sinusoidal oscillations under baseline conditions and after challenge with 1 mM ACh. Measurements were also obtained in strips pretreated with the calmodulin inhibitor calmidazolium (Cmz) or staurosporine (Stauro), a protein kinase C inhibitor. Elastance (E) and resistance (R) were calculated by fitting changes in T, L, and DeltaL/Deltat to the equation of motion. Hysteresivity (eta) was obtained from the following equation: eta = (R/E)2pif, where f is frequency. Finally, maximal unloaded shortening velocity during electrical field stimulation was measured in Cmz-pretreated and control tracheal strips. In tracheal strips, pretreatment with Cmz caused a significant decrease in the eta response to ACh challenge and in maximal unloaded shortening velocity measured during electrical field stimulation; Stauro decreased the T, E, and R response to ACh. In parenchymal strips, Cmz decreased the eta response, whereas Stauro had no effect. These results suggest that modifications in the contractile state of the smooth muscle are reflected in changes in the hysteretic behavior and that T and eta may be controlled independently. Second, inasmuch as changes in eta were similar in parenchymal and tracheal strips, the contractile element is implicated as the structure responsible for constriction-induced changes in the mechanical behavior of the lung periphery.

Acetylcholine↗

PubMed1998

A comparative study of elastic properties of rat and guinea pig parenchymal strips.

Constricted guinea pig (GP) airways are much less sensitive to changes in transpulmonary pressure (Ptp) than are those of the rat. The object of this study was to investigate whether differences in the mechanical behavior of the lung parenchyma could explain differences between the two species in the interdependence of the airway and parenchyma. Subpleural lung strips from guinea pigs and rats were excised and suspended in an organ bath. One end of each strip was attached to a force transducer and the other to a servo-controlled lever arm that effected length (L) changes in the strip. Sinusoidal oscillations at varying frequencies and amplitudes were applied at different resting tensions. Measurements of L and resting tension (T) were recorded during baseline conditions and after acetylcholine (ACh) challenge. Elastance (E) and resistance (R) were calculated by fitting changes in T and L to the equation of motion. During sinusoidal oscillations, E and R in the two species were different in both the unconstricted and constricted states. The effect of T on E was significantly different in rats and GPs; E was less dependent on T in GPs. Insofar as E is a measure of the load against which airway smooth muscle (ASM) contracts, this difference may represent a potential mechanism to explain why constricted GP airways are less sensitive to changes in Ptp.

Acetylcholine↗

PubMed1998

Human lung parenchyma responds to contractile stimulation.

Tissue resistance increases after agonist challenge. Parenchymal contractile cells may be the responsible element. We investigated the viscoelastic properties of human parenchymal strips before and after challenge with acetylcholine (ACh) (10(-)3 M). Thirteen subpleural strips were oscillated in the organ bath, and measurements of resistance (R), elastance (E), and hysteresivity (eta) were obtained. After physiologic measurements, tissues were fixed for morphometric and immunohistochemical analysis. We quantitated the volume proportion of alveolar, airway, and blood vessel wall in individual strips. Smooth-muscle-specific actin was identified using a monoclonal antibody and the volume proportion of actin quantitated by point counting. After ACh, there was a significant increase in tension (2.6 +/- 0.6%), R (11.0 +/- 1.8%), E (4.3 +/- 0.7%), and eta (8.2 +/- 2.4%) (p < 0.002). Four strips contained no identifiable airways, yet in strips with and without airways there was no difference in the magnitude of the mechanical response or in the volume proportion of smooth-muscle-specific actin in the alveolar walls. We conclude that human lung parenchymal strips respond to ACh challenge with changes in dynamic mechanical behavior. Furthermore, small airways are not required for such a response to occur. This implicates a direct contractile response at the level of the alveolar wall and/or the alveolar duct.

Acetylcholine↗

PubMed1998

Expression of lumican in human lungs.

The collagen-elastin-proteoglycan (PG) matrix is the key constituent of lung parenchyma and plays a major role in the mechanical behavior of lung tissues. However, the exact composition of the PG matrix in lungs has not yet been fully determined. In the present study we report the expression of leucine-rich repeat PGs in adult human lungs. PG extraction was performed on peripheral lung tissue from patients undergoing therapeutic lung resections. The samples were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting using antipeptide antisera specific to human lumican, decorin, biglycan, and fibromodulin. Control experiments to verify antiserum reactivity were performed with an extract of adult human articular cartilage, which is known to contain all four PGs. In all lung extracts analyzed, a single component of molecular weight 65 to 90 kD was detected for lumican. Decorin, biglycan, and fibromodulin were either not detected or were barely detectable in the lung extracts, but were readily visualized in the cartilage samples. Immunohistochemistry showed that lumican was diffusely present in peripheral lung tissue, mainly in vessel walls. These results suggest that lumican is a major component of the PG matrix in adult human lungs.

Aged↗