Biomedical subjects

J M Zahm

Publications and source records attributed to J M Zahm.

At least 37 records · Page 2Linked to original sources

PubMed1997

Cell migration and proliferation during the in vitro wound repair of the respiratory epithelium.

The respiratory epithelium is frequently injured by inhaled toxic agents or by micro-organisms. The epithelial wound repair represents a crucial process by which surface respiratory cells maintain the epithelial barrier integrity. The repair process involves both cell migration and proliferation, but as yet, the kinetic of these two mechanisms has not been extensively studied. Using an in vitro model of human respiratory epithelium wound repair, proliferative cell immunofluorescent staining and a computer-assisted technique allowing the tracking of living cells, we studied the cell proliferation and migration during the wound repair process. Respiratory epithelial cells were dissociated from human nasal polyps and cultured on a collagen I matrix. At confluency, a chemical wound was made on the culture. We observed that the cell mitotic activity peaked at 48 h after wounding (23% of the cells) and mainly concerned the cells located 160 to 400 microns from the wound edge. The migration speed was highest (35 to 45 microns/h) for the spreading cells at the wound edge and progressively decreased for the cells more and more distant from the wound edge. The temporal analysis of the cell migration speed during the wound repair showed that it was almost constant during the first 3 days of the repair mechanism and thereafter dropped down until the wound closure was completed (after 4 days). We also observed that over a 1-hour period, the intra-individual and interindividual variation of the cell migration speed was 43% and 37%, respectively. These results demonstrate that cell proliferation and cell migration during respiratory epithelial wound repair are differently expressed with regard to the cell location within the repairing area.

Cell Division↗

PubMed1997

Early alterations in airway mucociliary clearance and inflammation of the lamina propria in CF mice.

In cystic fibrosis (CF), whether cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction leads to decreased mucociliary clearance and mucus hypersecretion, before bacterial infection, remains an open question. To answer this question, we quantified in a blind trial the mucociliary transport velocity, the histological state, and the degree of inflammation of the tracheal mucosa in 23 cftr(m1HGU/cftr(m1HGU) transgenic mice (Dorin, J. R., P. Dickinson, E. W. F. W. Alton, S. N. Smith, D. M. Geddes, B. J. Stevenson, W. L. Kimber, S. Fleming, A. R. Clark, M. L. Hooper, L. Anderson, R. S. P. Beddington, and D. J. Porteous. Nature Lond. 359: 211-215, 1992) and in 30 control littermates housed in pathogen-free conditions. The nasal and tracheal transepithelial potential difference (PD) measured in basal conditions was significantly more negative in the cftr(m1HGU) mutant mice as compared with the control mice (nasal PD: -7.1 +/- 0.6 and -4.6 +/- 0.5 mV, respectively, P < 0.01; tracheal PD: -30.8 +/- 2.1 and -21.4 +/- 1.8 mV, respectively, P < 0.04). In the cftr(m1HGU)/cftr(m1HGU) mice, the mucociliary transport velocity was significantly lower (14.2 +/- 4.4 microm/mm, P < 0.04) compared with the control mice (30.6 +/- 5.9 microm/mm). The number of inflammatory cells in the lamina propria was significantly higher in the cftr(m1HGU)/cftr(m1HGU) mice (1048.7 +/- 124.7 cells/mm2, P < 0.03) compared with the control mice (640.5 +/- 58.2 cells/mm2). These results suggest that in CF, decreased airway mucociliary clearance and airway submucosal inflammation represent early alterations, before any airway infection.

Animals↗

PubMed1997

Revisited physicochemical and transport properties of respiratory mucus in genotyped cystic fibrosis patients.

We investigated the physicochemical and transport properties of sputum samples collected in physiotherapy from a well-documented group of 27 cystic fibrosis (CF) patients with identified CF genotypes. Sputum samples were characterized ex vivo for their water content, surface properties (surface tension and contact angle), rheologic properties (viscosity and elastic modulus), and transport properties (mucociliary and cough transport). These data were analyzed in relation to the clinical status of the patients (FEV1, FVC, Shwachman score, Brasfield score, nutritional status), their genotype, and the degree of infection of their sputa (leukocyte and Pseudomonas aeruginosa counts). We observed negative and significant correlations between mucociliary transport and elastic modulus of the patients' sputum (r = -0.63, p < 0.01), and between the cough transport and contact angle of the sputum (r = -0.81, p < 0.0001), respectively. The P. aeruginosa count was also significantly correlated with the sputum water content (r = -0.53, p < 0.02) as well as with the cough transport of the sputum (r = -0.62, p < 0.01). In CF patients with a sputum leukocyte count > 2,000/mm3, the sputum water content (p < 0.02), FEV1 (p < 0.05) and FVC (p < 0.02) were significantly lower than those of CF patients with a leukocyte count < or = 2,000/mm3. CF patients with a homozygous delta F 508 genotype had significantly greater values of sputum water content (p < 0.05), and cough-transport capacity (p < 0.05) than did heterozygous patients. No correlation was observed between the sputum properties and any of the clinical data. These results suggest that the control of infection should be emphasized in CF, since it can directly or indirectly modulate the degree of hydration, and therefore the physicochemical and transport properties, of airway secretions.

Adolescent↗

PubMed1996

CFTR is involved in membrane endocytosis but not in fluid-phase and receptor-mediated endocytosis in human respiratory epithelial cells.

Cystic fibrosis transmembrane conductance regulator (CFTR) protein has been reported to be a cAMP-regulator of plasma membrane recycling in epithelial cells overexpressing CFTR. To assess its role in the different endocytic processes in human respiratory epithelial cells, the rates of internalization of membrane, fluid-phase and receptor-mediator tracers were compared, under control conditions and after treatment with the cAMP agonist forskolin in normal and cystic fibrosis (CF) cells. In both control and treated-cells, CFTR was only present in the plasma membrane of normal but not in CF cells. Similarly, activation of Cl- efflux only occurred in normal and not in CF-treated cells. The rate of membrane endocytosis was significantly decreased by 35% in normal treated-cells, whereas it was not significantly decreased (12%) in CF-treated cells. Upon forskolin treatment, the decrease of the rate of both fluid-phase and receptor-mediated endocytosis was not significantly different between normal and CF cells. These results demonstrate that CFTR is involved in membrane endocytosis but not in fluid-phase and receptor-mediated endocytosis in human respiratory epithelial cells.

Cell Line↗

PubMed1996

Gelatinase B is involved in the in vitro wound repair of human respiratory epithelium.

Following epithelial injury, extracellular matrix undergoes imposing remodelings. We examined the contribution of matrix metalloproteinases, gelatinases A and B, in an in vitro wound repair model of human respiratory epithelium. Confluent human surface respiratory epithelial (HSRE) cells cultured from dissociated surface cells of human nasal polyps were chemically injured. Over the next 3 to 5 days, cells migrated onto the injured area to repair the circular wound. Repair kinetics of these wounds was monitored until wound closure occurred. Gelatinolytic activities were analysed in culture supernates and in cell protein extracts derived from repairing migratory and non repairing stationary cells. Small amounts of gelatinase A were expressed by HSRE cells, and variations of this gelatinase remained very weak for the time of the wound repair. In contrast, gelatinase B was upregulated during the wound repair process, with a maximum peak observed at wound closure. A marked gelatinase B activation occurred only in cells involved in the repair process. Gelatinase B was localized in some migratory basal cells, recognized by an anti-cytokeratin 14 antibody and located around the wound. We could not detect any gelatinase A in repairing or in stationary HSRE cells. Addition of the 6-6B monoclonal antibody, known to inhibit gelatinase B activation, to the culture medium during the repair process resulted in a dose-dependent decrease of the wound repair speed. These results suggest that gelatinase B, produced by epithelial cells, actively contributes to the wound repair process of the respiratory epithelium.

Adult↗

PubMed1996

Fibronectin and its alpha 5 beta 1-integrin receptor are involved in the wound-repair process of airway epithelium.

The cell migration that occurs during wound repair is dependent on modifications of the cell-matrix interaction in which extracellular matrix proteins and their receptors, the integrins, are involved. To study the interactions between airway epithelial cells and the extracellular matrix during the process of wound repair, we developed an in vitro wound model of human epithelial cells. Surface epithelial cells were dissociated from human nasal polyps and cultured on a type I collagen matrix. At confluency, a wound was made by the addition of 2 microliters of NaOH (1 N) to the cell culture. After the cell culture was washed, the wound area was recorded every 12 h for 96 h by a videomicroscopic technique. We calculated the wound-repair index that represents the decrease in the wound area per hour. Using immunofluorescence techniques, we first examined the localization, during wound repair, of fibronectin and of the beta 1-, alpha v-, alpha 2-, alpha 3-, and alpha 5-integrin subunits. Secondly, we carried out a series of wound-repair blocking experiments with the use of anti-integrin or anti-fibronectin antibodies diluted in the culture medium. We observed that fibronectin and the alpha 5- integrin subunit were exclusively expressed by the migratory cells in the wounded area. No difference in the localization of the alpha v-, alpha 2-, and alpha 3-integrin subunits was observed between the nonrepairing and repairing cells. The blocking experiments showed a significant decrease in the wound-repair index in the presence of either the anti-beta 1, -alpha 3, alpha 5, or the anti-fibronectin antibodies. Furthermore, the addition of fibronectin to the culture medium induced a significant increase in the wound repair index. These results suggest that fibronectin and the corresponding alpha 5 beta 1-integrin play an important role in the process of airway epithelium wound repair.

Antibodies↗

PubMed1996

Epithelial barrier integrity during in vitro wound repair of the airway epithelium.

The surface epithelium of the airway mucosa forms a continuous barrier to a wide number of noxious substances present in the lumen. The restoration of the barrier integrity after injury represents a key issue in the defense capacity of the airway epithelium. Using an in vitro wound repair model of the airway epithelium, we investigated the dynamic of the restoration of the epithelial barrier integrity during the wound repair process. Airway epithelial cells in culture were chemically wounded by sodium hydroxide. The immunolocalization of zonula occludens 1 (ZO-1), a cytoplasmic protein associated with the tight junctions, was examined during the wound repair process. Junctional integrity was examined by analyzing the transepithelial resistance (TER) and the permeability to [3H]mannitol and by visualizing the permeability to lanthanum nitrate during 5 days after injury. Immediately after injury, we simultaneously observed a 36.7% decrease in the TER and a 74.9% rise in the permeability to [3H]mannitol. In addition, lanthanum nitrate penetrated in the intercellular spaces in the repairing areas, which was also characterized by the absence of ZO-1 staining, as opposed to nonrepairing cells. TER and [3H]mannitol flux values as well as lanthanum nitrate and ZO-1 localizations were found to be similar to those observed in confluent cultures only 1 to 2 days after complete wound closure. This study demonstrates that using our culture model, confluent airway epithelial cells form a continuous and efficient barrier with tight junctions. Epithelial integrity is affected immediately after injury and is completely restored within 1 to 2 days after wound closure. During such a period of time, the airway epithelium may remain exposed to the noxious effect of environment in vivo, which can prevent the epithelial barrier restoration by modifying tight junction formation.

Cell Membrane Permeability↗

PubMed1996

Effects of rhDNase on purulent airway secretions in chronic bronchitis.

Recombinant human deoxyribonuclease (rhDNase) has been demonstrated to reduce in vitro the viscosity and to improve the transport capacity of purulent respiratory mucus in cystic fibrosis. During episodes of exacerbation of chronic bronchitis, the patients generally expectorate purulent mucus. Purulence of mucus is associated with an increased deoxyriboneucleic acid (DNA) concentration. We analyzed in vitro the potential effect of rhDNase on chronic bronchitis mucus transport by the ciliary activity (frog palate model) and by simulated cough (cough machine model), as well as the effect on mucus viscosity (controlled stress rheometer) and surface properties (contact angle). Purulent sputa collected from patients with chronic bronchitis (n = 15) during an episode of exacerbation were incubated for 30 min at 37 degrees C with either rhDNase at two different concentrations (final concentration 2 or 4 micrograms.mL-1) or placebo. The median mucociliary transport rate was significantly improved by rhDNase from 0.68 with placebo to 0.79 and 0.83 with 2 and 4 micrograms.mL-1 of rhDNase, respectively. A significant improvement in mucus cough transport was also induced by rhDNase from 25.5 mm with placebo to 27.0 mm with either 2 or 4 micrograms.mL-1 rhDNase. These improvements in mucus transport capacity were associated with alterations in the physical properties of the mucus. The mucus median control viscosity (511.4 Pa.s) and median contact angle (0.85 rd) significantly decreased to 112.5 Pa.s and 0.74 rd, respectively, in the presence of 4 micrograms.mL-1 of rhDNase. These findings demonstrate that recombinant deoxyribonuclease may exert a beneficial effect on mucus clearance in vitro by altering the viscosity and surface properties of the purulent chronic bronchitic sputum samples.

Bronchitis↗

PubMed1996

Wound repair-induced expression of a stromelysins is associated with the acquisition of a mesenchymal phenotype in human respiratory epithelial cells.

Wound repair involves many processes including cell migration, provisional matrix deposition, and remodeling. All of these processes are likely to be affected by matrix-modifying enzymes. Members of the matrix metalloproteinases family are physiologic mediators of the extracellular matrix degradation. Within this matrix metalloproteinases family, stromelysins can degrade many components of the extracellular matrix. We therefore tested the hypothesis that stromelysins could be produced by human surface respiratory epithelial (HSRE) cells repairing a wound. Experimental wounds were created in vitro in HSRE cell cultures and in situ in human bronchial mucosa maintained in organ culture. Stromelysin production was measured by casein-gel zymography in cellular protein extracts derived from repairing migratory and nonrepairing stationary cells of wounded HSRE cell cultures. Stromelysin-producing cells present in cell and tissue cultures were localized and characterized using immunofluorescence techniques. Zymographic and immunofluorescence techniques showed that stromelysins were produced exclusively by the migratory HSRE cells. Zymogram analysis showed that stromelysins were overexpressed and overactivated during the wound repair process, with the maximal production observed at wound closure. Using an anti-cytokeratin 14 antibody, we identified stromelysin-3-producing cells as basal epithelial cells. Moreover, most stromelysin-3-producing cells expressed the mesenchymal marker vimentin. Similar to stromelysins localization, vimentin-positive HSRE cells were exclusively located in the wounded area, and they were also positive to cytokeratin 14. In conclusion, stromelysins are suggested to be involved in HSRE cell migration and extracellular matrix remodeling during wound repair. Furthermore, stromelysin production by repairing HSRE cells is linked to the acquisition of a mesenchymal phenotype. HSRE cell migration may then be associated with the shift from an epithelial to a mesenchymal phenotype.

Bronchi↗

PubMed1995

[Effect of rhDNase on rheologic properties and transport capacity of mucus in cystic fibrosis].

Mucociliary transport is a major component of respiratory function and contributes greatly to the protection of the airways against infection. Cystic fibrosis is associated with severe abnormalities of the capacities of transport, due to the abnormal mucus and inflammatory changes of the epithelium. Recombinant human DNase I (rhDNase) has been demonstrated to reduce the viscosity of purulent cystic fibrosis respiratory mucus. To investigate the impact of rhDNase on transport capacities, we analysed ex vivo its effect on mucus transport by the ciliary activity and by the simulated cough. We measured in parallel the changes in rheological and physical properties of mucus. In 15 patients with cystic fibrosis, rhDNase was able in vitro to improve mucus transport capacities by simulated cough. The effect was dose-dependent and correlated with a decrease in viscosity and an improvement of surface properties of the mucus. A significant improvement of mucociliary transport was observed only in the subgroup of patients whose transport capacities were altered before incubation with rhDNase. Our findings suggest that rhDNase in vivo might benefit most to patients whose mucus transport capacities are altered, because of highly viscous and tenacious secretions.

Adolescent↗

PubMed1995

Regenerating cells in human airway surface epithelium represent preferential targets for recombinant adenovirus.

To investigate the efficiency of adenovirus-mediated gene delivery in regenerating human respiratory epithelium, we have performed infections with an E1- and E3-deleted type 5 recombinant adenovirus containing the Escherichia coli LacZ reporter gene on different culture models of regenerating human nasal polyp surface epithelium. These models included: (i) an ex vivo organ culture of nasal polyp tissue, (ii) an explant outgrowth cell culture, and (iii) an in vitro wound repair model, on dissociated cells. In ex vivo nasal polyp tissue, transduced cells were not detected in normal pseudostratified areas, but were found in areas of the surface epithelium with a morphology reminiscent of regenerating airway tissue. In the explant outgrowth cell culture, adenovirus-infected cells were preferentially detected at the periphery of the outgrowth. These transducible epithelial cells, representative of epithelial cells present in vivo during the process of surface airway epithelium regeneration, were shown to be migrating and poorly differentiated cells, which were proliferating or not. In the in vitro wound repair model, the efficiency of cell transduction was much higher in cells present in the wound area than in those far from the wound area. These results indicate that regenerating cells from human airway surface epithelium represent preferential targets for transgene expression, and suggest that efficiency of CFTR gene transfer by recombinant adenovirus vectors may be higher in regenerating CF airway mucosa than in normal tissue. However, since these cells do not show endogenous CFTR expression, the relevance of their preferential transduction for the functional correction of the ion transport defect in cystic fibrosis needs further investigations.

Adenoviridae↗

PubMed1995

Physical and functional properties of airway secretions in cystic fibrosis--therapeutic approaches.

The airway secretions which line the respiratory tract form a biphasic layer composed of an aqueous 'sol' layer and a more superficial 'gel' layer. In the sol layer, also described as the 'periciliary' layer or 'airway surface fluid', the cilia beat and relax. The lubricant sol layer enables the gel mucus present at the tips of the cilia to be transported by the ciliary beating of the ciliated cells. Due to difficulties with sampling, little is known about the physical and biochemical properties of the sol layer. The gel layer is composed of high molecular weight glycoproteins (mucins) linked with proteins and lipids. They form a gel network with a high water content (95%) and rheologic and physical properties (viscoelasticity, adhesivity) adapted in normal conditions to protect the airway mucosa, particularly through mucociliary transport. The adhesive properties of mucus, which are influenced by its lipid composition and degree of hydration, are very important in controlling the efficacy of mucus transport through ciliary activity and coughing. An intermediate viscosity and elasticity is required for optimal mucociliary transport. In obstructive airway diseases, either of genetic origin, such as cystic fibrosis (CF), or acquired (acute or chronic bronchitis), and particularly during inflammatory and infectious episodes, mucus dehydration is associated with an increase in secreted or transudated molecules and with marked augmentation of DNA content. These abnormalities contribute to the increased viscosity and adhesivity of the airway secretions and are responsible for their abnormally low transport rate by ciliary activity and for inefficient cough clearance. In view of these alterations in the physical and functional properties of CF airway secretions, pharmacologic approaches should aim to rehydrate the mucus and to restore normal mucociliary or cough transport by stimulating chloride ion secretion (i.e. using UTP or ATP associated with amiloride in order to block sodium ion and water reabsorption). During acute episodes of infection, recombinant human DNase (rhDNase) may rapidly prevent mucus stasis by improving its rheologic properties. Lubrication of the mucus at the sol phase interface by 'surfactant' therapy may also represent a very promising therapeutic perspective to reduce the hyperviscosity and hyperadhesivity of airway secretions.

Cilia↗

PubMed1995

Dose-dependent in vitro effect of recombinant human DNase on rheological and transport properties of cystic fibrosis respiratory mucus.

Recombinant human deoxyribonuclease (rhDNase) has been demonstrated to reduce the viscosity of purulent cystic fibrosis (CF) respiratory mucus, to improve pulmonary function and to reduce the risk of respiratory tract infectious exacerbations, but its effect on mucus transportability has not so far been investigated. The dose-dependent effect of rhDNase was analysed in vitro on mucus transport rate (tr) by ciliary activity and by simulated cough (cough transport (ct)), as well as on mucus viscosity and surface properties. Purulent CF sputa (n = 15) were incubated for 30 min at 37 degrees C with either rhDNase at three different concentrations (final concentrations 0.2, 2 or 20 micrograms.ml-1 of mucus) or placebo. No significant dose-dependent effect of rhDNase on the mucociliary transport rate was observed when the samples wer statistically analysed together. However, in the larger group of mucus samples (n = 11) with a low initial mucociliary transport rate, the latter was improved at each rhDNase concentration (tr0.2 = 0.69, tr2 = 0.88 and tr20 = 0.87) as compared to placebo (trp = 0.58). In the smaller group of mucus samples (n = 4) with high initial transport rate, a decrease in mucociliary transport rate was observed, particularly at the highest concentration rhDNase assayed, i.e. 20 micrograms.ml-1 of mucus (tr20 = 0.58) as compared to placebo (trp = 0.86). The mucus cough transport was increased by rhDNase (ct0.2 = 25 mm, ct2 = 27.5 mm and ct20 = 31 mm) as compared to placebo (ctp = 23.5 mm).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1995

Expression and localization of CFTR in the rhesus monkey surface airway epithelium.

The Rhesus monkey has been used as a model for evaluating the possibility of introducing the CFTR gene into the airway epithelium in vivo. We addressed the question of whether the simian airway surface epithelium exhibits a CFTR distribution and functional activity (ciliary beating frequency) similar to that of human airway surface epithelium. Expression of CFTR mRNA was demonstrated on Rhesus monkey tracheobronchial tissue by reverse transcription polymerase chain reaction (RT-PCR) analysis. By immunofluorescent light microscopy, CFTR was localized on the apical plasma membrane of ciliated cells as we previously described for human tracheobronchial surface epithelium. The ciliary beat frequency (CBF) measured on the explant of Rhesus monkey tracheobronchial tissue appeared to be similar to that of the CBF of human tracheobronchial ciliated cells. To compare the Rhesus monkey CFTR gene with that of the human, we sequenced parts of exon 13 (encoding the R domain) and exon 24 (encoding the C terminal part of the protein) of the Rhesus monkey CFTR gene. The nucleotide sequence identity with the human counterpart was found to be 98% and 94% respectively, although restriction enzyme differences allow discrimination between Rhesus monkey and human CFTR cDNA. Taken together, these results suggest that the airway epithelium of the Rhesus monkey is a suitable model of human respiratory epithelium for analyzing the effect of human CFTR gene transfer.

Amino Acid Sequence↗

PubMed1994

Airway epithelial damage and inflammation in children with recurrent bronchitis.

Inflammation and epithelial damage of the bronchial mucosa are frequently identified in children with bronchial diseases. Nevertheless, until now the quantitative assessment of the epithelial damage has never been studied in relation to clinical or respiratory function or mucus abnormalities. Bronchial biopsies and brushings were performed in 31 children with recurrent bronchitis and without atopia. The quantitative histologic data were compared with clinical results, the endoscopic appearance of the mucosa, ciliary beating frequency, mucus transport capacity, leukocyte count, and protein concentration in mucus samples. Most of the biopsies (87%) collected in this group of children without recent acute infections showed extensive epithelial damage. A significant correlation was observed between the degree of shedding and edema (p < 0.01). Bronchial epithelial edema was associated with a significantly decreased (p < 0.01) mucus transport rate. Inflammation of the submucosa was significantly correlated with lymphocyte epithelial infiltration (p < 0.01), total mucus protein content (p < 0.01), and local airway inflammation estimated by bronchoscopy. These results demonstrate that children with recurrent bronchitis develop a severe bronchial inflammation associated with an increased mucus protein content and a reduction in the mucociliary function.

Biological Transport↗

PubMed1994

Effect of extracellular ATP and UTP on fluid transport by human nasal epithelial cells in culture.

We have investigated the effect of both adenosine triphosphate (ATP) and uridine triphosphate (UTP) on the fluid transport, transepithelial electric potential difference (PD), and unidirectional chloride flux when applied apically to cultured human surface respiratory epithelial (HSRE) cells in a double-compartment chamber. The effects of ATP and UTP (both 100 microM) were examined in cells either untreated or pretreated with 100 microM amiloride in lactated Ringer's solution. ATP or UTP was added to the apical solution in a 100 microliters final volume. After a 2-h incubation period, the change in fluid transport was measured by weighing the apical fluid. Compared with control, amiloride blocked the fluid absorption by HSRE cells. The addition of ATP or UTP, either alone or after pretreatment with amiloride, induced a similar and significant increase in the apical fluid and chloride flux (P < 0.001 and P < 0.005, respectively). The changes in both fluid transport and chloride flux were accompanied by changes in PD. A blocker for chloride transport, 4,4'-diisothiocyano-2,2'-stilbene disulfonate, at 500 microM significantly blocked the ATP-stimulated fluid transport (P < 0.05) and chloride flux (P < 0.01). These results support the hypothesis that extracellular ATP and UTP increase the fluid transport by respiratory epithelial cells and may be useful in the hydration of mucus and respiratory mucosa.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1993

Epidermal growth factor promotes wound repair of human respiratory epithelium.

Reepithelialization of the airway mucosa is an essential step toward restoring a normal functional protective barrier during the repair of airway epithelial wounds. We investigated the role of epidermal growth factor in the wound healing of human surface epithelial cells cultured from nasal polyp explants on a type I collagen gel in serum-free defined medium. By using image analysis techniques, we measured the outgrowth area, the ciliated surface, the ciliary beating frequency, and the in vitro wound repair rate in the presence of different epidermal growth factor concentrations. We observed a significant dose-dependent increase in the outgrowth area (10-fold increase with epidermal growth factor doses of 0 to 20 ng/ml), in the percentage of the outgrowth surface covered by ciliated cells (30% without epidermal growth factor and 43% with epidermal growth factor 20 ng/ml) and in the ciliary beating frequency (12.6 to 14.5 Hz). The wound repair rate was improved by 29% in the presence of epidermal growth factor 10 ng/ml. These results suggest that epidermal growth factor could be involved in the wound repair process of the airway epithelium.

Journal Article↗

PubMed1993

Carbocisteine improves the mucociliary transport rate in rats with SO2-induced bronchitis.

In order to study the effect of carbocisteine on the mucociliary function of the respiratory tract, we performed a double-blind study on rats with SO2-induced (400 ppm) hypersecretion. During the experimental bronchitis, the treated group of rats received carbocisteine through a stomach tube at a dose level of 500 mg/kg for 15 days, whereas the untreated group of rats received distilled water. After killing the rats, and following lung excision, the respiratory mucus was scraped off and collected by using a glass capillary. The mucus degree of purulence was macroscopically estimated and the mucus transport rate was measured by using the frog palate technique. The mean mucus relative transport rate, measured on the frog palate, was 0.60 +/- 0.17 in the untreated group and was significantly higher (P < 0.01) in the treated group (0.73 +/- 0.14). Carbocisteine also significantly altered (P < 0.01) the mucus macroscopical aspect, leading to a decrease in the number of rats with purulent mucus. These results suggest that carbocisteine maintains an efficient mucus transport rate, leading to a less infected respiratory tract.

Animals↗