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PubMed2006

Relationship between calcium-activated chloride channel 1 and MUC5AC in goblet cell hyperplasia induced by interleukin-13 in human bronchial epithelial cells.

BACKGROUND: Interleukin (IL)-13 has recently been reported as the major T-helper 2 cytokine involved in mucus overproduction and oversecretion in allergic airways. However, the relationship between human calcium-activated chloride channel-1 (hCLCA1) and MUC5AC induced by IL-13 in vitro has not been fully investigated. OBJECTIVES: The present study examines whether IL-13 induces the expression of hCLCA1 in normal human bronchial epithelial (NHBE) cells. We also investigated the relationship between hCLCA1 and MUC5AC expression and the development of goblet cell hyperplasia (GCH). METHODS: NHBE cells were isolated from human bronchi, and cultured with an air-liquid interface. hCLCA1 and MUC5AC gene and protein expression, as well as GCH were examined in the cells after exposure to IL-13. RESULTS: Incubation with IL-13 for 14 and 21 days increased the total number of epithelial cells, the number of periodic acid-Schiff (PAS)-stained epithelial cells, the number of goblet cells, as well as expression of mRNA and protein of hCLCA1 and MUC5AC. The number of goblet cells with secretory granules also increased after 21 days of incubation with IL-13. Niflumic acid, a chloride channel inhibitor, reduced mRNA expression of hCLCA1 and MUC5AC, and reduced the number of PAS-positive cells after incubation with IL-13. NHBE cells exposed or not to IL-13 expressed IL-13 receptor alpha(1) (IL-13Ralpha(1)), and an antibody to IL-13 Ralpha(1) also reduced the number of PAS-positive cells after exposure to IL-13. CONCLUSIONS: IL-13 might induce the expression of MUC5AC and hCLCA1 gene and protein in well-differentiated NHBE cells. These cells might also differentiate into goblet cells and become hyperplastic.

Adult↗
PubMed2002

Acidomucin goblet cell expansion induced by parenteral nutrition in the small intestine of piglets.

Total parenteral nutrition (TPN) impairs small intestine development and is associated with barrier failure, inflammation, and acidomucin goblet cell expansion in neonatal piglets. We examined the relationship between intestinal goblet cell expansion and molecular and cellular indices of inflammation in neonatal piglets receiving TPN, 80% parenteral + 20% enteral nutrition (PEN), or 100% enteral nutrition (control) for 3 or 7 days. Epithelial permeability, T cell numbers, TNF-alpha and IFN-gamma mRNA expression, and epithelial proliferation and apoptosis were compared with goblet cell numbers over time. Epithelial permeability was similar to control in the TPN and PEN jejunum at day 3 but increased in the TPN jejunum by day 7. By day 3, intestinal T cell numbers were increased in TPN but not in PEN piglets. However, goblet cell expansion was established by day 3 in both the TPN and PEN ileum. Neither TNF-alpha nor IFN-gamma mRNA expression in the TPN and PEN ileum correlated with goblet cell expansion. Thus goblet cell expansion occurred independently of overt inflammation but in association with parenteral feeding. These data support the hypothesis that goblet cell expansion represents an initial defense triggered by reduced epithelial renewal to prevent intestinal barrier failure.

Animals↗
PubMed1998

Changes in mucosal goblet cell density in acute otitis media caused by non-typeable Haemophilus influenzae.

The correlation between secretory otitis media and increased goblet cell density in the middle ear mucosa is well established. Previous studies have shown that a single episode of acute otitis media caused by Streptococcus pneumoniae is followed by increased goblet cell density for a period of at least 6 months, conceivably predisposing a subsequent development of secretory otitis media. In this study, 25 rat middle ears were inoculated with non-typeable Haemophilus influenzae in order to determine the effect on mucosal goblet cell density. Five rats were killed on days 4, 8, 16, 60 and 180 postinoculation, followed by dissection, staining and whole-mount embedding of the middle ear mucosae. The goblet cell density was determined in 24 well-defined localities. Compared with 25 normal middle ears, the goblet cell density was significantly increased in almost all localities, at all days on which the animals were killed. Thus, increased goblet cell density and enlargement of mucosal areas containing goblet cells persisted 6 months after the acute incident. The induced increase of goblet cell density was higher than the increase following inoculation of S. pneumoniae. We conclude that acute otitis media caused by non-typeable H. influenzae is followed by a longstanding increase in mucosal secretory capacity, likely to predispose a subsequent development of secretory otitis media.

Animals↗
PubMed1995

Goblet cell hyperplasia induced by Strongyloides venezuelensis-infection in Syrian golden hamster, Mesocricetus auratus.

The goblet cell response was examined in the jejunum of the Syrian golden hamster, Mesocricetus auratus, following infection with an intestinal helminth, Strongyloides venezuelensis. After subcutaneous inoculation with 3000 infective larvae (L3), the number of adult worms in the small intestine remained stable up to day 20 and then decreased. Before infection, the number of goblet cells in the jejunum was about 70/10 villi. The number of goblet cells slowly increased, though not significantly, until day 20 post-infection, and then rapidly increased with an inverse relationship to the worm burden. By day 43, when adult worms were almost completely expelled, the number of goblet cells was about 3-fold higher than that of control animals. Similar vigorous goblet cell hyperplasia has not been reported in Strongyloides spp. infection in other experimental animals. Histochemical study revealed that goblet cells in the jejunum of Syrian golden hamsters, unlike those of other experimental animals, produced and released highly sulfated mucins.

Animals↗
PubMed1989

The whole-mount method as a technique for measuring experimental changes in airway goblet cell number.

The whole-mount staining method for mucous membranes was introduced as an experimental technique for measuring goblet cell density and for estimating the degree of goblet cell hyperplasia in the trachea of experimental animals. By this technique it was demonstrated that a single intratracheal instillation of lysed extract from human neutrophilic granulocytes in rats after 3 weeks caused a three-fold increase in the density of tracheal goblet cells as compared to control animals receiving saline. The increase is of 3-6 times greater magnitude than previously reported in similar experiments where the number of goblet cells was calculated from cross sections in a traditional manner. It was further shown that the increase in goblet cell density could be prevented if prednisone was given to the animals prior to and during the experiment. It is concluded that the whole-mount preparation method is a useful tool in the quantitation of airway goblet cells in experimental settings, and that it appears to be a more sensitive method than the traditionally used cross section techniques.

Animals↗
PubMed1993

Immune-mediated alteration of the terminal sugars of goblet cell mucins in the small intestine of Nippostrongylus brasiliensis-infected rats.

Alteration of terminal sugars of goblet cell mucins in the small intestinal mucosa was examined by lectin histochemistry in rats infected with Nippostrongylus brasiliensis. To see whether alteration of the nature of mucins was regulated by the local immune system, adult worms were implanted intraduodenally into recipient rats of various immune status. When 7-day-old ('normal') adult worms were implanted into naive euthymic rats, about 60% remained until day 7 and then were expelled. The number of goblet cells transiently decreased on day 5 and then progressively increased from day 9 onwards. In parallel with the hyperplasia, mucins in and released from goblet cells strongly expressed terminal N-acetyl-D-galactosamine which was specifically recognized by Helix pomatia agglutinin (HPA). When 13-day-old ('damaged') adult worms were implanted into naive euthymic rats, they were rapidly expelled by day 9 in association with hastened goblet cell hyperplasia and the alteration of terminal sugars of the mucins. Hastened worm expulsion, goblet cell hyperplasia and alteration of terminal sugars of the mucins were also observed when 'normal' worms were implanted into immune recipients. On the other hand, after implantation of 'normal' worms into hypothymic (rnu/rnu) rats, goblet cell hyperplasia or the alteration of terminal sugars of the mucins was almost completely absent. These results suggest that alteration of sugar residues of goblet cell mucins, especially the strong expression of terminal N-acetyl-D-galactosamine, is regulated by the host's immune system and seems to be important in the expulsion of N. brasiliensis.

Animals↗
PubMed2005

Composite glandular-endocrine cell carcinoma of the stomach. Report of two cases with goblet cell carcinoid component.

Composite glandular-endocrine cell carcinoma (CGECC) is recognized as a special type of gastric tumor composed of ordinary adenocarcinoma and neuroendocrine tumors. Goblet cell carcinoid (GCC) is a well-established type of appendiceal carcinoid, but the GCC component has not been well delineated in CGECC of the stomach. We report on two gastric CGECCs with a GCC component, analyzing the histologic components by immunohistochemistry. On initial biopsy, both cases were diagnosed as signet-ring cell carcinoma. However, the resected tumors consisted of three components: signet-ring cell carcinoma, GCC, and glandular adenocarcinoma. Although some signet-ring carcinoma cells and goblet carcinoid cells were indistinguishable by hematoxylin and eosin staining, E-cadherin immunostaining disclosed a definitive difference regarding the staining pattern in these cells. Both patients are well, with no recurrent tumor for about 10 years of follow-up. CGECC with a GCC component may have been confused with conventional adenocarcinoma with signet-ring cells. In cases of advanced signet-ring cell carcinoma with good prognosis, the possibility of such CGECC has to be considered.

Adult↗
PubMed2005

Effect of suplatast tosilate on goblet cell metaplasia in patients with asthma.

BACKGROUND: Goblet cell metaplasia is a pathologic characteristic of asthma, associated with excess mucus secretion. Interleukin (IL)-4 and IL-13 plays an important role in mucus hypersecretion. Suplatast tosilate (suplatast), an antiallergic agent, is a Th2 cytokine inhibitor that suppresses the synthesis of IL-4, IL-5, IL-13, and eosinophilic airway inflammation. OBJECTIVE: We examined the effects of suplatast on mucus production in bronchial biopsy specimens taken from asthmatic subjects. METHODS: Oral suplatast 300 mg daily, or placebo was administered for 3 months in a double-blind, parallel-group study in 25 patients with asthma. Biopsy specimens were evaluated at before and after treatment for alcian blue/period acid-Schiff (AB/PAS), MUC5AC staining in bronchial epithelium and IL-4+, IL-13+ cells as well as inflammatory cells in lamina propria. RESULTS: There were significant decreases in the percentage of AB/PAS (P < 0.01) and MUC5AC (P < 0.01) stained area in the suplatast group. These changes were accompanied by significant decreases in IL-4+ and IL-13+ cells in suplatast-treated subjects. Additionally, we have observed that the number of infiltrating eosinophils and CD4+ T cells significantly decreased. CONCLUSIONS: These findings suggest that suplatast prevents goblet cell metaplasia through modulation of Th2 cytokine production and the recruitment of eosinophils and CD4+ T cells in the asthmatic airways.

Administration, Oral↗
PubMed1984

Goblet cell density and vascularization during conjunctival transdifferentiation.

After debridement of the entire corneal epithelium with n-heptanol, two groups of rabbit corneas were segregated according to the extent of corneal neovascularization. Using a new topographic goblet-cell counting method and routine histology, the authors have reexamined the process of conjunctival transdifferentiation and compared the changes of goblet-cell density and morphology between nonvascularized and vascularized groups for a follow-up period of 167 days. Analysis of the total goblet-cell density disclosed that no goblet cells appeared on the corneal surface during the entire period of reepithelialization. After that, two phases were identified with respect to goblet-cell density: phase I (day 0-17) and phase II (after day 17). In phase I, both groups had a similar surge of goblet cells, with the peak occurring between days 7 and 11, suggesting little correlation with vascularization. Morphologic studies indicated the presence of a prominent centripetal cellular migration. In phase II, the nonvascularized group showed a rapid decline in goblet-cell density, and as a result the morphologic transdifferentiation into a cornea-like epithelium was completed on day 43. The changes of goblet cells to a smaller size and the presence of a more acidic mucin in the centrifugal receding zone, suggested that transdifferentiation on nonvascularized corneas is a process involving changes of cellular differentiation. In contrast, the vascularized group maintained a high plateau of goblet-cell density and an epithelium with conjunctival characteristics until day 167. This result disclosed that retardation of conjunctival transdifferentiation by corneal vascularization was in phase II. The possible role of vascularization in the modulation of conjunctival transdifferentiation is discussed.

Animals↗
PubMed1986

X-ray microanalysis of goblet cells in bronchial epithelium of patients with cystic fibrosis.

The elemental composition of goblet cells in bronchial epithelium was investigated by X-ray microanalysis. Biopsies were obtained from the left main bronchus, shock-frozen and freeze-substituted. In comparison to the control group (patients with chronic bronchitis), the goblet cells of patients with cystic fibrosis (CF) contained significantly more calcium. The analysis also indicated higher sulphur levels and lower potassium levels in the goblet cells of CF patients. Detailed analysis of a control biopsy showed that the calcium level in the mucous cells of the submucosal glands was considerably higher than that in the goblet cells. Although the data point to a higher calcium content of goblet cell mucus in CF patients, the significance of this finding for the calcium content of the tracheobronchial secretions in CF patients is unclear.

Adult↗
PubMed2004

Heterogeneity in the ultrastructure of the mucous (goblet) cells of the rabbit palpebral conjunctiva.

AIM: The purpose of this study was to assess objectively the ultrastructure of the secretory granules in rabbit conjunctival mucin-producing 'goblet' cells. METHOD: The upper eyelids from five young adult dioestrous female rabbits were dissected out, stretched onto a cardboard support and prepared for transmission electron microscopy by repeated application of an isotonic two per cent glutaraldehyde fixative at room temperature. Post-fixation treatment included osmium tetroxide and staining with uranyl acetate and lead citrate. Low magnification micrographs were taken of the goblet cells of the conjunctiva, printed at a magnification of approximately 6,000 and the number, size and features of the secretory granules assessed. RESULTS: Across the entire palpebral conjunctiva of all five rabbits, the majority of mucous cells displayed a goblet shape and the secretory granules were uniformly pale in staining. The average width of the goblet cells was 10.8 +/- 1.1 microm and the diameter of the secretory granules was 0.82 +/- 0.16 microm. However, in localised regions across the palpebral conjunctiva of two of the rabbits, some goblet cells were different in that the secretory granules had either a denser-staining core, in which some of the granules were densely staining (while others were pale) or most of the granules were densely staining. These mucous cells had an average diameter of 10.3 +/- 1.7 microm and the granule diameters averaged 0.88 +/- 0.01 microm. For these abnormal goblet cells, inflammatory cells were found in their immediate vicinity. Occasionally, goblet cells were seen to be in the process of degranulation with associated apparent cell necrosis and the mucin granule diameter was close to 1 microm. CONCLUSIONS: The ultrastructure of the mucin-containing secretory granules of the conjunctival mucous cells is not necessarily homogeneous in character and further attention needs to be given to the effects of localised inflammation in the tissue and to possible hormonal influences.

Animals↗
PubMed1987

Endocytosis and vesicular traffic in fetal and adult colonic goblet cells.

Structural and functional differences between adult and fetal colonic goblet cells have not been clearly defined. To compare the binding, uptake, and intracellular pathway of internalized apical membrane in fetal and adult goblet cells, cationic ferritin (CF) was used as a nonspecific probe. The initial distribution of membrane anionic sites was determined in segments of proximal and distal colon from fetal (18-22 days) and adult rats that were fixed prior to a 10-minute exposure to CF at 4 degrees C. Uniform binding along the apical membrane and microvilli was noted at all ages. To assess uptake and intracellular transport, segments of proximal and distal colon from fetal and adult rats were exposed to CF for 10 minutes at 4 degrees C prior to a saline wash and incubation in saline or Liebovitz L-15 medium for 3, 6, 15, 30, or 60 minutes at 37 degrees C. In addition, fetal rats between 18 and 22 days gestation (birth) were exposed to CF continuously for 10-30 minutes via an intracaecal injection. The results showed extensive uptake of CF in the fetal goblet cells and a more variable intracellular pathway than in with the adult. Within 3 minutes, numerous CF positive vesicles and tubules were present within the apical cytoplasm as well as interspersed among the secretory granules of the fetal goblet cell. Most of these vesicles were smooth surfaced, although some were coated. By 15 minutes, CF was frequently seen in multivesicular bodies, and occasionally in vacuoles in the vicinity of the Golgi. No CF was detected in Golgi cisternae.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Quantitative study of goblet cells in the upper lobe of the normal human lung.

Goblet-cell density and distribution were studied in ten specimens of the human adult lung. The bronchial tree of the left upper lobe was dissected, and the bronchial mucosa separated and stained by the whole-mount periodic acid-Schiffalcian blue method. There was a significant fall in the goblet-cell density from the proximal to the distal airways. In the upper division, the number decreased from 144 cells per field (second generation) to 80 cells per field (14th generation), and in the lingular division it decreased from 137 (fourth generation) to 77 cell (18th generation). The overall goblet-cell density for the upper lobe was 113 cells per field, corresponding to 6,400 cells per square millimeter. No particular pattern in cell distribution was noticed; the cells were irregularly distributed all along the bronchial tree without any well-defined distribution pattern. In the ten lung specimens studied, goblet-cell density did not correlate with smoking habit, sex, or age.

Adult↗
PubMed1995

Guanylin, an endogenous ligand for C-type guanylate cyclase, is produced by goblet cells in the rat intestine.

BACKGROUND & AIMS: Guanylin activates an intestinal guanylate cyclase (GCC) and stimulates electrolyte movement across the gut epithelium. Cells expressing guanylin messenger RNA have been localized to the epithelial cell layer of the intestine; however, the identity of the guanylin-producing cells has not been determined. The aim of this study was to identify cells that express guanylin in the rat intestine. METHODS: Antibodies were raised against defined proguanylin epitopes, evaluated by Western blotting, and used for immunoperoxidase histochemistry. RESULTS: Guanylin-like immunoreactivity was localized to a subset of goblet cells. In the small intestine, most, perhaps all, goblet cells in the villi were immunopositive, as were some goblet cells in upper crypts; however, goblet cells deep within crypts were unlabeled. In the colon, goblet cells clustered in the necks and around the openings of crypts were immunopositive, whereas (as in the small intestine) goblet cells in deeper crypt regions were unlabeled. In some animals, immunoreactive columnar epithelial cells were also observed in the colon (although such cells were not apparent in the small intestine). Relative labeling of columnar cells varied from animal to animal. CONCLUSIONS: Guanylin is expressed in mature goblet cells. If secreted in conjunction with mucin, it could play a role in the hydration of mucus.

Animals↗
PubMedDate not supplied

Qualitative tear film and conjunctival goblet cell assessment of cats with corneal sequestra.

OBJECTIVES: To evaluate the tear film qualitatively and conjunctival goblet cell numbers in cats with and without corneal sequestra. ANIMALS STUDIED AND PROCEDURES: This was a prospective evaluation of 11 cats with corneal sequestra and 14 control eyes that were either the contralateral normal eye when the sequestrum was unilateral or from control cats of similar age with no ocular disease. All cats in this study were examined by a veterinary ophthalmologist. The ophthalmic examinations included a neuro-ophthalmic evaluation, Schirmer tear tests, fluorescein staining, tear film break-up times, applanation tonometry, biomicroscopy, and indirect ophthalmoscopy. The palpebral conjunctiva at the dorsal nasal, ventral nasal, dorsal temporal and ventral temporal fornices were biopsied after topical anesthetic was applied to the cornea and conjunctiva. The conjunctival biopsies were fixed in formalin and sectioned routinely and stained with hematoxylin and eosin, and periodic acid-Schiff. These slides were examined by light microscopy by a blinded examiner. Goblet cell numbers were compared to conjunctival basal epithelial cell numbers by region. The goblet cell numbers by region from the eyes with sequestra was statistically compared to those from eyes without sequestra, with a student's paired t-test. Conjunctival swabs were collected from the cats with corneal sequestra and submitted for polymerase chain reaction for Herpes felis, Chlamydia psiitticia, and Mycoplasma felis. The corneal sequestra were removed by surgical keratectomy and fixed and stained routinely, and examined by light microscopy. RESULTS: No neurologic abnormalities were detected in any of the cats. The Schirmer tear tests (eyes with sequestra 14+/-5.1 mm/min; normal eyes 15+/-6.8 mm/min) and intraocular pressures (eyes with sequestra 21+/-6.6; normal eyes 22+/-5.8) were within normal reference ranges for cats. Biomicroscopic examinations revealed varied sizes and depths of brown- and amber-colored corneal sequestra. No abnormalities were noted on indirect ophthalmoscopic examinations. The tear film break-up time was 21 s (+/-12) for the normal eyes (n=14) and 14 s (+/-13) in eyes with corneal sequestra (n=11). The average goblet/epithelial cell ratios by region for the normal eyes and the eyes with sequestra respectively were 0.66, 0.56 for the dorsal nasal fornix, 0.68, 0.57 for the ventral nasal fornix, 0.63, 0.48 for the temporal dorsal fornix, and 0.55, 0.49 for the temporal ventral fornix. There were no significant differences in tear film break-up times and goblet cell numbers in eyes with corneal sequestra and those without sequestra. Three conjunctival swabs from two of 11 cats with sequestra were positive with PCR for Herpes felis virus. These included one cat with bilateral sequestra and one cat with unilateral corneal sequestrum. CONCLUSIONS: The pathogenesis of feline corneal sequestra does not appear to be linked primarily to abnormal goblet cell numbers, qualitative tear film abnormalities, and accelerated tear film break-up time.

Animals↗
PubMed1975

Goblet cells, enterochromaffin cells, superficial gastric-type epithelium and antral-type glands in the gallbladder.

From a material derived from routine investigations, 40 gallbladder specimens were selected in which metaplastic cells had been observed. All the cholecystectomies were performed for gallstones. Of the patients 6 were male and 34 female. The mean age was 51.2 years. 36 specimens revealed goblet cells, enterochromaffin cells were found in 22, antral-type (pseudopyloric) glands in 23 and islands of gastric surface epithelium in 15 specimens. Histochemical methods to visualize sulphated, non-sulphated acid and neutral mucins were used. Ordinary gallbladder epithelium showed a predominance of sulphated mucosubstance. Sporadic goblet cells usually occurred in so-called goblet cell areas which, if small, were located in the tops of folds and only when larger also in the deeper parts of folds. As the goblet cell area enlarged, the relative proportion of sulphated mucin diminished and correspondingly non-sulphated acid mucin increased, while neutral mucin was noted both in the goblet cells and in the intervening columnar cells. In 20 specimens there were enterochromaffin cells in the goblet cell areas while only 2 specimens revealed enterochromaffin cells outside the goblet cell area. The glands outside the neck region of the gallbladder resembled gastric antral glands in their general architecture and in the appearance of individual cells. A part from frequent enterochromaffin cells (in 12 specimens) the glands are composed of mucous cells. The glandular cells contained sulphated mucin, non-sulphated acid and neutral mucin chiefly in the peripheral parts of glandular cells. In the gallbladders there were numerous abnormalities in some areas: heavy mucous secretion, goblet cells, enterochromaffin cells and superficial gastric-type epithelial spots were seen chiefly in the upper parts of folds, while proliferation of antral-type glands occurred in the basal parts. It is probable that some common pathological factors are responsible for the frequent simultaneous appearance of different types of metaplasia.

Adult↗