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PubMed2005

Reduced three-dimensional motility in dehydrated airway mucus prevents neutrophil capture and killing bacteria on airway epithelial surfaces.

Cystic fibrosis (CF) lung disease is characterized by persistent lung infection. Thickened (concentrated) mucus in the CF lung impairs airway mucus clearance, which initiates bacterial infection. However, airways have other mechanisms to prevent bacterial infection, including neutrophil-mediated killing. Therefore, we examined whether neutrophil motility and bacterial capture and killing functions are impaired in thickened mucus. Mucus of three concentrations, representative of the range of normal (1.5 and 2.5% dry weight) and CF-like thickened (6.5%) mucus, was obtained from well-differentiated human bronchial epithelial cultures and prepared for three-dimensional studies of neutrophil migration. Neutrophil chemotaxis in the direction of gravity was optimal in 1.5% mucus, whereas 2.5% mucus best supported neutrophil chemotaxis against gravity. Lateral chemokinetic movement was fastest on airway epithelial surfaces covered with 1.5% mucus. In contrast, neutrophils exhibited little motility in any direction in thickened (6.5%) mucus. In in vivo models of airway mucus plugs, neutrophil migration was inhibited by thickened mucus (CF model) but not by normal concentrations of mucus ("normal" model). Paralleling the decreased neutrophil motility in thickened mucus, bacterial capture and killing capacity were decreased in CF-like thickened mucus. Similar results with each mucus concentration were obtained with mucus from CF cultures, indicating that inhibition of neutrophil functions was mucus concentration dependent not CF source dependent. We conclude that concentrated ("thick") mucus inhibits neutrophil migration and killing and is a key component in the failure of defense against chronic airways infection in CF.

Bronchi↗
PubMed1996

Drug diffusion through cystic fibrotic mucus: steady-state permeation, rheologic properties, and glycoprotein morphology.

One manifestation of cystic fibrosis (CF) is the presence of a viscid mucus secretion in the lungs. The clearance of this mucus is significantly slower than in "normals" due to uncoordinated beating of the cilia and the increased viscosity of the mucus. In these studies, the permeabilities of p-aminosalicylic acid, isoniazid, and pyrazinamide through unpurified CF respiratory mucus and through purified pig gastric mucus solutions were compared in order to evaluate the relative barrier properties of these mucus solutions. These model compounds, while not often used clinically in CF, are used in other pulmonary diseases and have the potential to be administered by inhalation delivery systems. Permeability studies were carried out in Side-Bi-Side diffusion cells fitted with a custom membrane holder capable of retaining the mucus solutions. Permeabilities through CF mucus solution and its fractions were compared to those measured through buffer and reconstituted purified pig gastric mucus. There were 28--75% decreases in drug permeability when pig gastric mucus was replaced by different CF mucus solutions. This indicates that optimal drug delivery directly to the lungs must take into account the decreased drug transport rate across diseased mucus in addition to drug loss due to binding to the glycoproteins or inefficient delivery via aerosolization. Transmission electron microscopy revealed minor differences in the glycoprotein strand structure between reconstituted pig gastric mucus and CF mucus primarily with regard to glycoprotein chain length and extent of branching. Similar viscoelastic behaviors between the CF gel fraction and synthetic CF mucus were observed. This model CF mucus system can simulate diseased mucus and can be utilized for in vitro studies to optimize drug permeability.

Aminosalicylic Acid↗
PubMed2004

[From when on can fungi be identified in nasal mucus of humans?].

BACKGROUND: Fungal spores are frequent in air and their occurrence in the nasal mucus appears to be a common finding within the adult population, as we were able to show in recent studies. 91,3 % of CRS patients but also healthy controls grew positive fungal cultures out of their nasal mucus. The potential role of fungal elements in nasal mucus for the pathogenesis of CRS, with or without polyposis, is currently investigated intensely and discussed very controversially. However, it was still unknown, as of when fungi could be cultured from nasal mucus in humans. We attempted to identify this point of time, in the nasal mucus of neonates. METHODS: In our study we examined nasal mucus from 30 neonates immediately after birth, on the first and fourth day post partum, and after two and four months of life. The samples obtained with sterile cotton swabs were cultured on agar plates. Fungal cultures were identified either conventionally by microscopy or with molecular techniques. To show whether fungi in nasal mucus of newborns were acquired by contamination during birth, mucus of the maternal vagina was examined as well. RESULTS: Just after birth we found in 6 of 30 (20 %) of our neonates positive fungal cultures out of their nasal mucus, in 3 of them Candida albicans, probably due to contamination passing the maternal vagina as cultures of vaginal mucus of their mothers were positive for Candida albicans too. Positive fungal cultures were obtained in 2 of 29 (7 %) neonates on the second and in 4 of 26 (15 %) neonates on the fifth day of life. In all our cases initial presence in nasal mucus contamination just after birth or on the second day of life was limited to one day only. None of the 12 of 30 (40 %) neonates with positive fungal cultures from nasal mucus in the first 5 days of life showed clinical symptoms of nasal fungal colonisation. Besides Candida albicans, Penicillium sp., Cladosporium cladosporioides, Acremonium polychromum, Beauveria bassiana and Epicoccum nigrum could be detected in the first 5 days of life. After the second month of life, examination of nasal mucus yielded positive fungal cultures in 8 of 11 (72 %), after four months even 17 of 18 (94 %) of babies, with a wide array of different species. CONCLUSIONS: Fungi can be cultured from nasal mucus as soon as contact with the environmental air exists. Furthermore, a transfer of fungi from the mother's birth canal into the nose during birth is possible. Presence of fungal spores is common but not persistent in the nose of babies in the first days of life. However, after four months the situation is similar to the one in adults: fungal cultures can be obtained from almost everyone's nose. Therefore fungal spores must be considered a normal content of nasal mucus. Fungal spores are inhaled with every breath, some stick to the mucus, are transported to the nasopharynx and swallowed. This does not cause any clinical symptoms and is therefore not a pathological finding at all.

Adult↗
PubMed1992

Effects of anti-acid secretory agents on various types of gastric mucus.

Total, acidic, and sulfated mucus contents in the gastric mucosa were evaluated after administration to rats of ranitidine and pirenzepine, antagonists of gastric parietal cell receptors; omeprazole, a proton-pump/inhibitor; and misoprostol, a prostaglandin E1 preparation. Total gastric mucus content was significantly decreased by ranitidine, but contents of acidic mucus and sulfated mucus showed a slight increase. Total mucus and acidic mucus contents were slightly increased after administration of pirenzepine, whereas the sulfated mucus content was significantly increased. The total gastric mucus content was significantly decreased after administration of omeprazole, but acidic mucus increased slightly and sulfated mucus increased significantly. All mucus contents were unchanged after administration of anti-acid secretory dose of midoptodyol. After administration of either ranitidine or omeprazole, the neutral mucus content decreased, but the total acid and sulfated mucus contents were not decreased. Changes in various mucus contents following inhibition of acid secretion are different for different drugs, and it was suggested that production of neutral mucus and secretion of acid mucus were reduced by strong inhibition of acid secretion.

Animals↗
PubMedDate not supplied

Bronchial mucus properties in lung cancer: relationship with site of lesion.

OBJECTIVE: To compare the biophysical properties of mucus from the left and right mainstem bronchi in patients undergoing diagnostic bronchoscopy because of a unilateral radiological abnormality. It was hypothesized that abnormalities in the properties of mucus would be greater on the side with the lesion and that this would be most obvious in patients with unilateral lung cancer. PATIENTS AND METHODS: Bilateral paired samples of bronchial mucus were taken from 38 nonatopic patients (aged 59.8+/-12.6 years) including 16 nonsmokers, 14 current smokers and eight exsmokers (more than one year). Twenty of the 38 patients had a radiologically defined unilateral abnormality. Eight of these 20, including one nonsmoker, had lung cancer. The viscoelastic properties of the collected mucus were determined by magnetic microrheometry, and the analysis was carried out without knowledge of the histological diagnosis or source. RESULTS: The rheological properties of mucus strongly suggested which was the abnormal side. Within the group of 20 patients with a unilateral radiological abnormality, mucus from the side of the lesion had a lower value of the loss tangent, tan d100 (P=0.004), indicating greater mucus recoil. This is consistent with poor mucus cough clearability on the lesion side. All eight cancer patients fit this mucus rheological pattern with a lower value of tan d100 on the affected side (P=0.007). Four of the five other patients with a similar mucus abnormality were categorized as high cancer risk by other criteria, while six of seven patients with mucus that did not have this abnormality were considered to be lower risk. Based on the mucus analysis done at the time of the bronchoscopy, two of the 'noncancer' patients initially designated as high risk had cancer detected after several months of follow- up. Only two of the 18 patients without a defined unilateral lesion fit the mucus 'cancer pattern'. CONCLUSIONS: These findings are consistent with the hypothesis that either abnormalities in mucus properties may represent a risk factor for the development of lung cancer or that bronchial mucus abnormalities may be associated with products secreted by the tumours that, in turn, may suppress mucus clearance.

Adult↗
PubMed2005

A distinct carbonic anhydrase in the mucus of the colon of humans and other mammals.

We have collected gastrointestinal, mainly colonic, mucus from humans, guinea pigs, rats, and normal and carbonic anhydrase II (CAII)-deficient mice. In the mucus of all species, substantial CA activity was present. Using antibodies against human CA isoforms we found that the human mucus CA differs from cytosolic CAI and CAII, membrane-bound CAIV, and the secreted CAVI of saliva. The high sensitivity of mucus CA to acetazolamide rules out its identity with cytosolic CAIII. Partial sequences obtained from the purified human mucus CA show similarity, but not identity, with human CAI, and clear differences from the other known CAs. Additional evidence concerning the CA isoform present in mucus was obtained for the mucus CA of other species and was derived from: (1) the mucus of CAII-deficient mice, whose high CA activity confirms that it is not CAII that is responsible; (2) the inhibitory effect of iodide, which shows that mucus CA from mice, guinea pig and humans does not have the high anion sensitivity of CAI; (3) the inactivating effect of 0.2% SDS on guinea pig, mouse and human mucus CA, ruling out the SDS-resistant CAIV; and (4) the partitioning of guinea-pig mucus CA into the water phase in Triton X114 phase separation experiments, which also argues against its identity with membrane-bound CAs, such as CAIV. A comparison of colonic mucus CA activity in normal and germ-free rats indicates that the mucus CA is not of bacterial origin but is produced by the gastrointestinal tissues. We conclude (from its immunoreactivity, from iodide inhibition and from partial amino acid sequences) that mucus CA of human origin probably represents an isozyme, which is specific for mucus and is not identical with the known CA isozymes. The results obtained for mucus CA of other species collectively point in the same direction.

Acetazolamide↗
PubMedDate not supplied

The effect of tasuldine, a bronchosecretolytic agent, on mucus rheology and clearability and the interaction with acetylcholine in ferrets.

Tasuldine (Ts) is an orally active bronchosecretolytic agent shown to be clinically effective in human studies. Tasuldine decreases the sialomucin content of the mucus and, in animal studies, this modulation of the glycopeptide correlates with decreased mucus viscosity. The aim of this study was to evaluate the effect of tasuldine on mucus viscoelasticity and correlate the rheological changes to mucociliary and cough clearability. Tracheal mucus samples were collected from anaesthetized adult ferrets by a modification of the cytology brush technique. Mucus was collected prior to and following administration of either vehicle (normal saline) or Ts (10 mg/kg i.v.), and followed by acetylcholine (ACH) challenge (ca. 4 ml of 10(-2)M i.v., slow infusion). The analysis included magnetic microrheometry to measure the viscosity and elasticity of microlitre quantities of mucus. Mucociliary transportability (NFPTR) was measured by means of the frog palate assay and mucus collection rates (mg/min) were used as an indirect measure of secretion rate. The principal index of mucus rigidity, log G*, decreased with tasuldine infusion (P = 0.014) and further decreased with ACH (P = 0.002). In simple terms, the mucus became less rigid or more deformable with tasuldine administration, thus benefiting clearability based on predictions from model studies. The changes observed with acetylcholine alone were consistent with a classic secretagogue response--the outputting of a large volume of watery mucus. NFPTR increased with tasuldine treatment, and even further with acetylcholine; however, the combination of Ts and ACH resulted in a decrease in NFPTR close to baseline, which was likely due to the fact that the resulting mucus was too liquid for maximal mucociliary efficiency. The index of mucus flux (mg/min) was very much elevated with ACH compared with control; this was not the case with Ts. This indicates that tasuldine, despite improving the rheological properties of the mucus, did not stimulate hypersecretion, as was the case for acetylcholine. The changes in mucus rheology with infused tasuldine can be considered beneficial with respect to their effects on predicted mucociliary and cough clearability, supporting the clinical effectiveness of this type of mucolytic therapy in airway diseases such as chronic bronchitis. The study also illustrates the potential danger of overliquification of mucus.

Acetylcholine↗
PubMed1987

N-acetylneuraminic acid and hostile mucus infertility.

A total of 39 samples of hostile mucus, as defined by postcoital examination, were examined for N-acetylneuraminic acid (NANA) deficiency, as measured by the enzymatic addition of NANA, spermatozoal penetration and immobilization. Only 56.7% of the mucus samples were deficient in NANA and this did not correlate with spermatozoal penetration or immobilization, which were negatively correlated. Thus, as the spermatozoal hostility in the mucus decreases, spermatozoal penetration increases. This finding also applies to hostile mucus not deficient in NANA. In contrast, resialylation of NANA hostile mucus, deficient and not deficient in NANA, although not enhancing spermatozoal penetration, did reduce spermatozoal immobilization. Thus, components of the mucus deficient in NANA and/or the lack of unbound NANA may contribute to mucus hostility, but it is not the only hostile factor. In addition, SEM studies of NANA-deficient mucin before and after resialylation were shown to have similar structures. Hence ultrastructural changes are not apparent in NANA-deficient mucin, and this supports the previous finding that NANA deficiency does not impede spermatozoal penetration. The spermatozoa from the husbands of the infertile couples formed three distinct groups in terms of spermatozoal penetration and immobilization in normal donor mucus. One group demonstrated normal levels of spermatozoal penetration and immobilization in donor mucus. A second group was demonstrable in which spermatozoal penetration was similar to that in the wife's hostile mucus, but had a normal level of spermatozoal immobilization. In the third group, both spermatozoal penetration and immobilization in donor mucus were similar to that in the wife's hostile mucus. The results demonstrate that not all hostile mucus is deficient in NANA, and that other unknown factors are involved. In addition, there are also male factors which may impede spermatozoal penetration and/or result in the inability of the spermatozoa to survive in normal donor mucus.

Cervix Mucus↗
PubMed1995

Sperm binding to the human zona pellucida after migration through human cervical mucus.

During lactational amenorrhea a special type of cervical mucus, similar to that found during the luteal phase, is produced. This mucus, however, is able to support sperm migration. In the study described, the ability of spermatozoa to bind to the human zona pellucida (hZP) after migration through periovulatory and post-partum mucus was studied. Mucus was obtained from exclusively breastfeeding women in amenorrhea at 30, 60, 120 and 180 days post-partum. Periovulatory mucus samples from normally cycling women were used as a control. Flat capillary tubes were filled with BWW culture medium at the top and cervical mucus at the bottom. The tubes were immersed in a semen reservoir and the spermatozoa allowed to migrate through the mucus for 3 h into the culture media. Then the spermatozoa were coincubated with 3-4 hZP for 30 min and the number of bound spermatozoa per zona was counted. Periovulatory cervical mucus had an average Insler score of 14 +/- 0.5 as compared to 4.6 +/- 0.4 for post-partum mucus. Spermatozoa recovered from periovulatory mucus were always able to bind to the hZP in only 68 +/- 7% of the cases. Moreover, spermatozoa recovered from post-partum mucus bound to the ZP in lower numbers than did spermatozoa recovered fro periovulatory mucus (p < 0.03). These results suggest a greater ability of sperm-hZP binding after migration through periovulatory mucus and they also indicate that sperm binding to the ZP is possible even after sperm migration through a low quality mucus.

Cell Adhesion↗
PubMed1994

The gastroduodenal mucus barrier and its role in protection against luminal pepsins: the effect of 16,16 dimethyl prostaglandin E2, carbopol-polyacrylate, sucralfate and bismuth subsalicylate.

Mucus and bicarbonate secretions have been widely implicated as an important pre-epithelial protective barrier against autodigestion of the gastric mucosa by acid and pepsin. Evidence from several independent studies shows there is a continuous layer of resilient viscoelastic mucus gel adherent to the surface of the gastroduodenal mucosa. The median thickness of the adherent gastric mucus layer in humans is 180 microns, range 50-450 microns. The epithelial bicarbonate secretion permeates the unstirred matrix of mucus gel neutralizing luminal acid and establishing a pH gradient within the gel. In the duodenum, evidence supports the mucus bicarbonate barrier as a major protective mechanism against acid aggression. The adherent mucus gel, by acting as an effective 'permeability' barrier to pepsin, protects the underlying sensitive mucosa from digestion. However, pepsin slowly digests mucus gel at its luminal surface to produce soluble degraded mucin. In a rat gastric damage model in vivo, pepsin in excess digests the gastric mucus barrier sufficiently rapidly to outweigh new mucus secretion and lead to breaching of the mucus barrier with the formation of small punctate ulcers in the epithelium accompanied by mucosal haemorrhage. The mucus secretagogue 16,16 dimethyl prostaglandin E2 and the muco-adhesive carbopol-polyacrylate both fully protected the mucosa against pepsin damage by enhancing the protective properties of the mucus barrier. Sucralfate and bismuth subsalicylate were partially effective in protection against pepsin damage but this protection was mainly mediated at the level of the mucosa. In peptic ulcer disease, there is increased mucolytic (mucus degrading) activity in gastric juice and this is associated with an impaired mucin polymeric structure and a weaker mucus barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

16,16-Dimethylprostaglandin E2↗
PubMed1995

Growth of Escherichia coli K88 in piglet ileal mucus: protein expression as an indicator of type of metabolism.

The physiological and molecular responses of enterotoxigenic Escherichia coli K88 strain Bd 1107/7508 during growth in piglet ileal mucus and lipids extracted from mucus were studied in terms of growth rate, protein expression, and rate of heat production. E. coli K88 multiplied at maximum speed in mucus and in lipids extracted from mucus. By two-dimensional gel electrophoresis of [35S]methionine-labelled cells, it was demonstrated that the synthesis of a subclass of 13 proteins was changed at least fourfold during exponential growth in mucus compared with growth in M9 minimal medium. Ten of these proteins were repressed, while three were induced, and one of the induced proteins was identified as heat shock protein GroEL. Furthermore, two-dimensional analysis of E. coli K88 cells grown on lipids extracted from mucus revealed a set of lipid utilization-associated proteins. None of these was induced fourfold during exponential growth in mucus. Microcalorimetric measurements (monitoring the rate of heat production) of E. coli K88 grown in mucus indicated metabolic shifts in the stationary phase, in which five of the lipid utilization-associated proteins were expressed at a higher level. An isogenic E. coli K88 fadAB mutant deficient in fatty acid degradation genes grew as well as the wild type on mucus and mucus lipids. The heat production rate curve of the mutant grown in mucus differed from that of the wild type only during the stationary phase. From these results it was concluded that protein expression is influenced when E. coli K88 is grown in piglet ileal mucus rather than in M9 minimal medium. Lipids extracted from ileal mucus can serve as a substrate for E. coli K88 but appear not to be utilized during exponential growth in mucus. Stationary-phase cells metabolize fatty acids; however, the functional purpose of this is unclear.

Anaerobiosis↗
PubMed1983

Stimulation of canine gastric mucus secretion with intraarterial acetylcholine chloride.

This study was undertaken to develop an easily reproducible gastric mucus secretory model that would elicit maximal mucus secretion without gross mucosal injury. Acetylcholine chloride (50 micrograms/min) was infused intraarterially into a chambered wedge of exteriorized corpus mucosa via a branch of the gastrosplenic artery for 1 h. An alkaline secretion, pH 8.28 +/- 0.48, was produced and consisted of water (40-60 ml/h), electrolytes (Na+, K+, Cl-), soluble mucus, and a mucus gel (4-10 mm thick). Mucus was quantitated by monitoring the secretion of newly synthesized glycoproteins, radiolabeled with [3H]glucosamine and sodium [35S]sulfate. A transient increase in deoxyribonucleic acid efflux, and mucosal permeability as measured by albumin movement, occurred, both of which were reversible upon cessation of acetylcholine chloride infusion. The gastric epithelium was normal histologically, except for occasional apical vacuoles present only in interfoveolar mucus cells. Transmission electron microscopy revealed diminished numbers of apical mucus granules and greatly enlarged intercellular spaces in some mucus cells. Histochemically, the mucus gel consisted of alternating layers of sulfate-rich and sulfate-poor glycoproteins. This model provides a copious amount of mucus that is ideal for biochemical analysis and determination of mucus structure. It allows one to distinguish soluble mucus, gel mucus, and unsecreted granule-bound mucus.

Acetylcholine↗
PubMed2006

The Mucus Slurper: A novel tracheal tube that requires no tracheal tube suctioning. A preliminary report.

OBJECTIVE: The buildup of mucus within the endotracheal tube (ETT) progressively reduces its internal volume. We devised the Mucus Slurper as an integral part of the tracheal tube to aspirate all mucus automatically at its distal tip. DESIGN AND SETTING: In vitro, and in vivo studies in sheep at the National Institutes of Health, NHLBI, PCCMB. SUBJECTS: Six sheep, sedated, paralyzed, and mechanically ventilated INTERVENTIONS: We evaluated the Mucus Slurper in vitro, and we evaluated its efficacy and safety in three healthy sheep during 24 h on volume-controlled mechanical ventilation in comparison to three sheep managed with open tracheal tube suctioning. MEASUREMENTS AND RESULTS: In vitro: with the Mucus Slurper connected to a source of vacuum of 450-500 mmHg the total volume of a single suction lasting 0.1, 0.2, and 0.3 s was, respectively, 75.4 +/- 7.9, 114.5 +/- 4.6, and 143.4 +/- 8.7 ml; with the measured vacuum within the lumen of the Mucus Slurper ring of 37 cmH2O. In vivo: during mechanical ventilation we aspirated through the Mucus Slurper 13.4 +/- 3.3 cc mucus/24 h. During the course of single aspiration the Mucus Slurper never affected the level of applied PEEP. The tracheal tube was free of tracheal secretions in the Mucus Slurper group while thin secretions were found within the ETT in the control group. CONCLUSION: The Mucus Slurper is a novel device designed to keep the tracheal tube and proximal trachea free of mucus. In studies in sheep lasting 24 h the Mucus Slurper was safe and prevented all mucus accumulation within the ETT.

Animals↗
PubMed1999

Relative roles of convection and chemical reaction for the disposition of formaldehyde and ozone in nasal mucus.

The mucociliary apparatus is an important respiratory-tract defense system that may provide significant protection of the underlying epithelium from gases and vapors. Limiting-case calculations were performed to determine the significance of convective mucus transport and chemical reaction for formaldehyde (HCHO) and ozone (O(3)) in rat nasal respiratory epithelial mucus. Less than 4.6% of absorbed HCHO can be bound to amino groups (serum albumin) after 20 min of exposure. Thus, at the slowest measured mucus flow rates in rats, approximately 1 mm/min, a fluid element of mucus could travel more than 2 cm before binding 5% of absorbed HCHO, by which time the element would probably leave the nose (the site of toxic responses). In other calculations, HCHO removed by chemical reaction from a volume of mucus exposed for longer times was determined to be less than 0.54% of that removed by mucus flow (convection). Given the solubility of HCHO in mucus (water) and estimates of total mucus flow, however, as much as 22-42% of inhaled HCHO may be removed by total mucus flow. Alternately, O(3) dissolved in mucus would react completely with unsaturated fatty acids in 8.3 x 10(-4) s, in which time the mucus could flow no more than approximately 0.42 microm at the maximum reported flow rate of 30 mm/min. Even if a volume of mucus is flushed by net flow in 1 s, the amount of O(3) removed by flow would only be 0.12% of that removed by chemical reaction. Finally, based on the solubility of ozone, less than 8.0 x 10(-5)% of inhaled material could be removed from the nose by mucus flow. These results indicate which mucociliary processes are significant in site-specific dosimetry modeling.

Algorithms↗
PubMed2003

Milk bioactive peptides and beta-casomorphins induce mucus release in rat jejunum.

Intestinal mucus is critically involved in the protection of the mucosa. An enzymatic casein hydrolysate and beta-casomorphin-7, a mu-opioid peptide generated in the intestine during bovine casein digestion, markedly induce mucus discharge. Because shorter mu-opioid peptides have been described, the effects of the opioid peptides in casein, beta-casomorphin-7, -6, -4, -4NH2 and -3, and of opioid neuropeptides met-enkephalin, dynorphin A and (D-Ala2,N-Me-Phe4,glycinol5)enkephalin (DAMGO) on intestinal mucus secretion were investigated. The experiments were conducted with isolated perfused rat jejunum. Mucus secretion under the influence of beta-casomorphins and opioid neuropeptides administered intraluminally or intra-arterially was evaluated using an ELISA for rat intestinal mucus. Luminal administration of beta-casomorphin-7 (1.2 x 10(-4) mol/L) provoked a mucus discharge (500% of controls) that was inhibited by naloxone, a specific opiate receptor antagonist. Luminal beta-casomorphin-6, -4 and -4NH2 did not modify basal mucus secretion, whereas intra-arterial administration of beta-casomorphin-4 (1.2 x 10(-6) mol/L) induced a mucus discharge. In contrast, intra-arterial administration of the nonopioid peptide beta-casomorphin-3 did not release mucus. Among the opioid neuropeptides, intra-arterial infusion of Met-enkephalin or dynorphin-A did not provoke mucus secretion. In contrast, beta-endorphin (1.2 x 10(-8) to 1.2 x 10(-6) mol/L) induced a dose-dependent release of mucus (maximal response at 500% of controls). DAMGO (1.2 x 10(-6) mol/L), a mu-receptor agonist, also evoked a potent mucus discharge. Our findings suggest that mu-opioid neuropeptides, as well as beta-casomorphins after absorption, modulate intestinal mucus discharge. Milk opioid-derived peptides may thus be involved in defense against noxious agents and could have dietary and health applications.

Animals↗
PubMed2002

Mixed nasal mucus as a model for sinus mucin gene expression studies.

OBJECTIVE/HYPOTHESIS: It is necessary to obtain sinus mucus from the paranasal sinus cavities to study mucin gene expression occurring in the sinuses during chronic sinusitis. This requires an invasive procedure to access the sinus cavity. There are embryological as well as histological similarities between nasal and sinus epithelia; therefore, we postulated that the mucin expression in the secreted nasal and sinus mucins might be similar. Nasal mucus, which can be obtained easily, could then replace sinus mucus in these studies. STUDY DESIGN: Sinus and nasal mucus from six patients with chronic sinusitis were analyzed in this study. METHODS: High-molecular-weight glycoproteins (mucins) were isolated and purified by sequential density gradient centrifugation in caesium chloride (CsCl). Enzyme-linked immunosorbent assay was performed to identify the antigenic identity of these mucins. RESULTS: The MUC2, MUC5AC, and MUC5B mucin genes were all expressed in the nasal and sinus mucus secretions. Antigenic studies showed an inverse relationship between MUC2 and MUC5AC expression in nasal and sinus mucus secretions. The MUC5B gene was the major mucin gene expressed in sinus mucus but not in nasal mucus. Expression of MUC2 was significantly higher in sinus mucus. Expression of MUC5AC was different between nasal and sinus mucus. CONCLUSIONS: Individual mucin expression in sinus and nasal mucus was markedly different. From this preliminary study, we conclude that nasal mucus is not a suitable substitute for sinus mucus in sinus mucin gene studies and that different pathological processes are taking place in nasal and sinus tissue in chronic sinusitis.

Chronic Disease↗
PubMed1988

Roles of motility, chemotaxis, and penetration through and growth in intestinal mucus in the ability of an avirulent strain of Salmonella typhimurium to colonize the large intestine of streptomycin-treated mice.

Previously, it had been shown that an avirulent strain of Salmonella typhimurium, SL5316, with wild-type lipopolysaccharide (LPS) was a far better colonizer of the streptomycin-treated CD-1 mouse large intestine, was far more motile, did not bind to mouse intestinal mucus nearly as well as, but penetrated through a layer of intestinal mucus in vitro far better than an almost isogenic LPS-deficient transductant, SL5325. In the present investigation, a nonflagellated transductant, SL5681, and a nonchemotactic transductant, SL5784, were isolated from SL5316 and tested for relative colonizing ability versus SL5316 (smooth) and SL5325 (rough) in streptomycin-treated mice. In addition, the Salmonella strains were tested for their ability to grow together in cecal intestinal mucus and in cecal luminal contents, for their tumbling and swimming activities after growth in cecal mucus, and for their ability to adhere to and travel through cecal mucus in vitro. The data show that the nonflagellated and nonchemotactic derivatives colonized large intestine nearly as well as their parent and were far better colonizers than the LPS-deficient mutant, that all the strains grew equally well in cecal mucus but did not grow in cecal luminal contents, and that cecal mucus-grown strains lost tumbling and swimming activities. Furthermore, the LPS-deficient strain adhered to cecal mucus far better but penetrated mucus far worse than did the nonflagellated transductant, the nonchemotactic transductant, and the parent. Thus, motility and chemotaxis do not appear to play a major role in the ability of the avirulent S. typhimurium strains to colonize the mouse large intestine, colonization may require growth in cecal mucus but does not depend on growth in cecal luminal contents, growth in cecal mucus inhibits S. typhimurium motility, and increased adhesion of the LPS-deficient mutant to cecal mucus and its poor ability to penetrate cecal mucus may play a role in its poor intestine-colonizing ability.

Animals↗
PubMed1991

Role of phospholipid lining on respiratory mucus clearance by cough.

Phospholipid lining, present at the respiratory mucus-mucosa interface, may have an important role in the protective function of the airways by its abhesive properties and may also facilitate mucus transport. To mimic respiratory mucus-mucosa interface, monolayers of three different forms of phosphatidylglycerol (PG) have been deposited on glass slides by the Langmuir-Blodgett technique. Mucus adhesion and clearance by cough of mucus on these PG-coated or noncoated surfaces have been analyzed and compared, using frog respiratory mucus as "normal" mucus. Among the three PG types studied, the phosphatidylglycerol distearoyl, which is the phospholipid with the longest saturated fatty acid chain, was found to significantly improve the mucus cough clearance by decreasing the mucus work of adhesion compared with the noncoated surfaces. On the other hand, phosphatidylglycerol dipalmitoyl did not improve mucus cough clearance although it decreased mucus adhesion, and phosphatidylglycerol dioleyl did not improve either mucus cough clearance or mucus adhesion.

Animals↗