Histochemical localization of prostaglandin synthetase in human exocrine glands

Prostaglandin synthetase activity is histochemically detected in the epithelial cells of the human prostate, seminal vesicle, and deferential ampulla. The addition of the specific inhibitor indomethacin to the incubating medium strongly reduces the staining reaction. The presence of exogenous substrate in the medium is not required for the reaction, since identical results are observed following incubation with and without arachidonic acid. The presence of the enzyme appears to be related to the secretion of prostaglandins into the seminal fluid, but there is a possibility that some prostaglandins influence the metabolism of the secreting cells themselves. The localization of prostaglandin synthetase in the ductal epithelia of human salivary glands is related to a possible regulatory role of the prostaglandins upon the reabsorptive activity of the ductal cells.     

Morphology of the exocrine glands of the frog skin

Frog skin contains three distinct types of exocrine glands: granular (poison), mucous, and seromucous. The granular gland forms a syncytial secretory compartment within the acinus, which is surrounded by smooth muscle cells. The mucous and seromucous glands are easily identifiable as distinct glands. The serous and mucous secretory cells are arranged in a semilunar configuration opposite the ductal end and are filled with granules. Within the acinus, located at the ductal pole of the gland, are distinct groups of cells with few or no granules in the cytoplasm. In both the mucous and seromucous gland there is a cell type with abundant mitochondria; the one in the mucous gland is located in the region adjacent to the secretory cells. The duct of these glands is two-layered, with the individual cells appearing morphologically similar to the layers of the skin epithelium as the duct traverses the skin. The duct appears to be patent throughout its length. The morphological heterogeneity and distinct distribution of the cell types within the gland acinus may be indicative of a functional heterogeneity that allows the production of distinctly different types of secretion from the same gland type, depending on the type of stimulus.     

Effects of chronic furosemide treatment on rat exocrine glands

It has been suggested that a defective chloride transport is the primary cellular basis for the disease cystic fibrosis (CF). Therefore, the effects of chronic furosemide treatment on the structure and function of rat exocrine glands were investigated. X-ray microanalysis of the submandibular gland showed an increase in the cellular Ca and Mg concentrations, and a decrease in the cellular Cl concentration. Transmission electron microscopy showed intracellular accumulation of mucus and the presence of mucus in acinar and ductal lumina. The volume of saliva secreted by the submandibular gland after pilocarpine stimulation was markedly reduced in furosemide-treated animals; the salivary concentrations of Na and Ca were higher, and that of K was lower, than in control animals. The protein concentration in submandibular saliva was not significantly affected. The response of the submandibular gland to isoproterenol stimulation was reduced in furosemide-treated animals. In the parotid gland, chronic furosemide treatment caused an accumulation of immature zymogen granules in the acinar cells and a decrease in the cellular Cl concentration. In the pancreas, the acinar lumen was dilated and completely filled with secretory material, and the acinar cells contained less Na and somewhat less Cl than in control animals. The chronically furosemide-treated rat shows a number of parallels with other animal models for CF, in particular the chronically reserpinized rat. There is also agreement with the human disease itself.     

The human intestinal B-cell response

The intestinal immune system is chronically challenged by a huge plethora of antigens derived from the lumen. B-cell responses in organized gut-associated lymphoid tissues and regional lymph nodes that are driven chronically by gut antigens generate the largest population of antibody-producing cells in the body: the gut lamina propria plasma cells. Although animal studies have provided insights into mechanisms that underpin this dynamic process, some very fundamental differences in this system appear to exist between species. Importantly, this prevents extrapolation from mice to humans to inform translational research questions. Therefore, in this review we will describe the structures and mechanisms involved in the propagation, dissemination, and regulation of this immense plasma cell population in man. Uniquely, we will seek our evidence exclusively from studies of human cells and tissues.     

The prevalence and character of the muscularis mucosae of the human urinary bladder

We report the results of a histological evaluation of 335 consecutive autopsy specimens of apparently normal urinary bladder for the presence of a complete, partial or minimal muscularis mucosae. There were 164 females (49%) and 171 males (51%), ranging in age from 20 weeks of gestation to 102 years. A muscularis mucosae was present in 117 bladders (35%). The female to male ratio was 2:1, with 45% of female and 25% of male bladders containing a muscularis mucosae. The muscularis mucosae was complete in one case (1%), partial in 23 cases (6%) and minimal in 93 cases (28%). The occurrence of a partial or complete muscularis mucosae was ten times more likely in women than men. The presence of a muscularis mucosae in both women and men was not associated with any known disease process, nor was it related to patient age.     

The organization of the lamina muscularis mucosae in the human esophagus

The structural organization of the lamina muscularis mucosae of the human esophagus was studied by light microscopy and scanning electron microscopy (SEM). The organization of the lamina muscularis mucosae varied considerably among the cervical, the thoracic, and the abdominal part of the esophagus. In the cervical part, the lamina muscularis mucosae was not well developed and only islets of the smooth muscle bundles were scattered within the connective tissue. In the thoracic part, the lamina muscularis mucosae consisted of several layers of smooth muscle bundles, individual muscle cells of which ran in a longitudinal direction. In the abdominal esophagus near the cardia, the muscular bundles in the lamina muscularis mucosae ran in various directions forming a reticular configuration. The differences in density and arrangement of the lamina muscularis mucosae are discussed in relation to the swallowing of food and submucosal invasion of esophageal cancer.     

Configuration of myoepithelial cells in various exocrine glands of guinea pigs

To study the configuration of myoepithelial cells, we isolated glandular endpieces of various guinea pig glands by collagenase, and visualized the myoepithelial cells by immunohistochemistry for actin, or by Bodipy-phallacidin, under both a light microscope and laser scanning confocal microscopes. In parotid and mandibular glands, the glandular acini were small (about 20–30 m diameter) and spherical, and each acinus had one or two myoepithelial cells attached that were stellate in shape (central cell body and four to six thin processes). Most of the basal surface of the glandular cells was not covered by myoepithelial cells, and processes often extended to the neighboring acinus. The tubular glandular endpieces of the major sublingual gland, which secretes a mucous substance, were almost fully encircled by bandlike myoepithelial cells (about 3–6 m wide). Although there were many differences between the lacrimal gland and the Harderian gland (e.g., the secretory product of the lacrimal gland was mucous, and glandular lumina were narrow; the Harderian gland secreted lipids and showed wide lumina), the outer contours of both glandular endpieces were the same (about 50–100 m diameter, ellipsoid or spherical in shape). In both glands, 5–20 stellate myoepithelial cells were attached onto a glandular endpiece, and their arrangement had a lacy appearance. Actin filaments in myoepithelial cells aggregated and formed bundles in the broad processes and cell bodies. The bundles ran across the cell body, but there was no point where the bundles converged. In the arborization, some distal processes reversed their direction. We conclude that the configuration of myoepithelial cells depends on the outer contour of the glandular endpieces rather than on the secretory material or luminal width. The variety of myoepithelial cell configurations in the different exocrine glands we examined suggests that it is quite difficult to assign to myoepithelial cells the general role of expelling secretory products from glandular lumina. These cells seem to maintain the contour of the glandular endpieces, serving as the exoskeleton of the endpieces.     

Oncocytic cardiomyopathy in an infant with oncocytosis in exocrine and endocrine glands

An 11 week old female infant with congenitally malformed eyes died from intractable cardiac arrhythmia. The heart showed extensive oncocytic transformation of myocytes, and this distinctive cardiomyopathy affected the conduction system. Oncocytes were found also in endocrine (pituitary, thyroid) and exocrine (submandibular, sublingual, minor salivary) glands. There is morphologic evidence that the lesions were caused early in gestation, possibly by a viral infection such as rubella.     

Actual characteristics of the glands distributed in the lamina propria mucosae of the fowl esophagus.

We performed histological and histochemical investigations on the glands distributed in the lamina propria mucosae of the fowl esophagus and demonstrated their actual characteristics. 1. Glandular cells of the compound tubular glands located in the lamina propria mucosae contained a number of fine pepsinogen granules. 2. Reactions to neutral, weak and strong acid mucopolysaccharides, neutral mucus type II and III and sialomucin were evidently positive in these cells. 3. Based on the facts in 1) and 2), we consider that the glands located in the fowl esophagus are undifferentiated gastric glands. 4. The same glands possessed no parietal cells. 5. We demonstrated that the esophageal cardiac glands in the lamina propria mucosae of human esophagus were undifferentiated gastric glands, and they possessed parietal cells. These glands were confirmed in humans alone among the mammalia. 6. The significance of the existence of the same kind of gland in human and fowl esophagus is extremely important. 7. PAS-positive substance in the above-mentioned glands in the fowl esophagus contains sulfuric, acid, neutral mucopolysaccaride and neutral mucus of type II and III but no glycogen. The compound tubular glands distributed in the lamina propria mucosae of the fowl esophagus have been described as mucous glands. We performed histochemical investigation and demonstrated that these glands were undifferentiated gastric glands.     

The ultrastructure of periductal connective tissue and distinctive populations of collagen fibrils associated with ductal epithelia of exocrine glands

The ultrastructure of the connective tissue around the intraglandular ducts was observed in rat exocrine glands. Connective tissue with a dense population of collagen fibrils was found either around the ducts and blood vessels (perivasculoductal connective tissue; PVDCT) as in the lacrimal and salivary glands and liver, or solely surrounding the ducts (periductal connective tissue; PDCT) as in the exocrine pancreas, whereas the interlobular and intralobular interstitium of the glands-except for the liver-contained substantially fluid-filled spaces without collagen fibrils. The PVDCT and PDCT of these glands contained two populations of collagen fibrils-fibroblast-associated and epithelium-associated-although the development and density of these fibrils varied considerably in individual glands. Both populations of collagen fibrils were most developed in the lacrimal glands, in which the basal aspects of the ductal epithelium and the basement membrane showed considerable undulation associated with a distinctive peribasement membrane zone with amorphous matter and a small population of the fibrils. In the parotid and submandibular glands, both populations were distinct, though poorly developed. In the exocrine pancreas and hepatic Glisson's sheath, the two populations of collagen fibrils were moderately developed, and the basal aspects of the ductal epithelium were characterized by prominent invaginations in which the multilaminar basement membranes and the epithelium-associated collagen fibrils were frequently engulfed. These observations provide evidence that the two populations of collagen fibrils around the ducts are found universally in exocrine glands, and support the hypothesis of the collagen fibril-synthesizing and -secreting ability of ductal epithelial cells.     

Primary B-cell lymphoma of salivary glands and its relationship to myoepithelial sialadenitis

A detailed morphologic and immunohistochemical study has been carried out on salivary glands excised from 20 cases in which the initial histologic diagnosis was either myoepithelial sialadenitis (MESA) or salivary gland lymphoma (SGL). The results have shown that these cases, except one that had been diagnosed as MESA, showed a spectrum of changes ranging from focal lymphoid infiltrates, designated as early MESA, through established MESA with dense, extensive lymphoid infiltration, to lymphoma. The distribution of the lymphoid infiltrate in early MESA was related to ducts and mimicked Peyers patches. In established MESA, this infiltrate became confluent with the formation of prominent epimyoepithelial islands. The evolution of lymphoma was characterized by an expanded population of centrocyte-like (CCL) cells that showed light chain restriction. Like other lymphomas of mucosa-associated lymphoid tissue, to which they bear a striking resemblance, salivary gland lymphomas may remain localized for prolonged periods with a tendency to local recurrence rather than to distant spread. These properties may be explained by the histogenesis of these tumors from CCL cells that appear to be of similar lineage of splenic marginal zone cells.     

Transplantation of side population cells restores the function of damaged exocrine glands through clusterin

Stem cell-based therapy has been proposed as a promising strategy for regenerating tissues lost through incurable diseases. Side population (SP) cells have been identified as putative stem cells in various organs. To examine therapeutic potential of SP cells in hypofunction of exocrine glands, SP cells isolated from mouse exocrine glands, namely, lacrimal and salivary glands, were transplanted into mice with irradiation-induced hypofunction of the respective glands. The secretions from both glands in the recipient mice were restored within 2 months of transplantation, although the transplanted cells were only sparsely distributed and produced no outgrowths. Consistent with this, most SP cells were shown to be CD31-positive endothelial-like cells. In addition, we clarified that endothelial cell-derived clusterin, a secretory protein, was an essential factor for SP cell-mediated recovery of the hypofunctioning glands because SP cells isolated from salivary glands of clusterin-deficient mice had no therapeutic potential, whereas lentiviral transduction of clusterin restored the hypofunction. In vitro and in vivo studies showed that clusterin had an ability to directly inhibit oxidative stress and oxidative stress-induced cell damage. Thus, endothelial cell-derived clusterin possibly inhibit oxidative stress-induced hypofunction of these glands. Stem Cells2012;30:1925-1937.     

Polyclonal B-cell activation is related to exocrine manifestations of primary Sj?gren's syndrome

Twenty-four female and four male patients with primary Sj?gren's syndrome were examined in order to evaluate possible correlations between the exocrine disease manifestations and polyclonal B-cell activation parameters. All patients were examined three times over a 4-month period and none of them received any systemic medical treatment. Van Bijsterveld scores were negatively correlated to unstimulated whole salivary flow rate (sialometry) values (P less than 0.01) and break-up times (BUT) (P less than 0.01), while unrelated to Schirmer-1 values. Unstimulated sialometry values were, in addition, positively correlated to Schirmer-1 values (P less than 0.01), while BUT were unrelated to Schirmer-1 and unstimulated sialometry values. P-IgG levels were positively correlated to van Bijsterveld scores (P less than 0.01) and negatively correlated to break-up times (P less than 0.05), while unrelated to unstimulated sialometry and Schirmer-1 values. P-IgG levels were furthermore positively correlated to levels of P-IgM (P less than 0.05), P-IgA (P less than 0.05), serum IgM-RF (P less than 0.001) and serum ANA (P less than 0.01). Levels of P-IgM-RF were positively correlated to van Bijsterveld scores (P less than 0.01), but to none of the other exocrine manifestations. We conclude that the plasma levels of B-cell products seem to correlate positively with the degree of ocular involvement in patients with primary Sj?gren's syndrome, indicating a relationship between the immunoinflammatory processes and the mucosal damage.     

Ontogenesis of the secretory immune system and innate defence factors in human parotid glands

Immunoglobulin-producing cells and epithelial expression of secretory component (SC), amylase, lysozyme (Ly) and lactoferrin (Lf) were studied by immunohistochemistry to obtain information about the development of mucosal immunity. Tissue specimens were obtained from 20 fetal and 40 postnatal parotid glands. (1) Fetal specimens. Occasional IgM- and IgA- but no IgD-, IgG- or IgE- producing cells were seen (ratios, IgM:IgA:IgD:IgG:IgE approximately 4:1:0:0:0). The IgAl subclass dominated (median 90%, range 50-95%) and these cells were mostly J-chain-positive (median 97%, range 94-98%). Only few IgA2-producing cells were seen (median 10%, range 5-50%) and they were also mostly J-chain-positive (median 99%, range 98-100%). Amylase, Ly and Lf were most prominent in early fetal life, while only small amounts of SC were present. (2) Postnatal specimens. Secretory component increased markedly along with a growing number of IgA- and IgD-producing cells (IgA:IgM:IgD:IgG:IgE approximately 4:2:1:1:0). The IgAl subclass remained predominant (median 65%, range 50-90%) although the proportion of IgA2-positive cells tended to be raised (median 35%, range 10-50%). Most IgAl (median 97%, range 67-100%) and IgA2 (median 94%, range 75-100%) cells were J-chain-positive. These features probably reflected local activation of the immune system in response to environmental factors. The amount of amylase, Ly and Lf decreased shortly after delivery, perhaps because the cellular stores were emptied by postnatal increase in secretory activity.     

The organization of the communication routes between the epithelium and lamina propria mucosae in the human esophagus

Morphological studies examined communication routes between the epithelium and lamina propria mucosae in the human esophagus, using a series of techniques including silver staining, immunohistochemistry, transmission electron microscopy, and scanning electron microscopy (SEM). For SEM, tissue blocks were treated with either osmium/ultrasonication or NaOH. Observations showed the esophageal papillae to be arranged regularly in a mostly longitudinal row. The reticular fibers, consisting of fibrils approximately 40 nm in diameter, were situated just beneath the epithelial basal lamina. They showed a positive reaction with a type III collagen antibody, and formed a continuous sheet 2-3 microm thick with dense networks. This sheet as well as the epithelial basal lamina had numerous foramina of diameters of 3-5 microm. Immune cells such as lymphocytes and Langerhans cells were situated around these foramina. The foramina were situated both around papillae and the duct orifice of the esophageal gland. In addition, lymphoid follicles surrounded the duct of the esophageal gland. The structural characteristics around the duct appear to be those of duct-associated lymphoid tissue (DALT). Thus, these foramina in the epithelial basal lamina and reticular fiber sheet may represent important communication routes between the epithelium and lamina propria mucosae. In addition, they may play an important role in the mucosal immune response in the human esophagus.     

Innervation of human nasal glands

Summary The innervation of human nasal glands was investigated with the electron microscope in 14 males and 11 females using osmium and permangante fixed material. Acetylcholinesterase activity was localized electron microscopically in formalin fixed tissues.It was found that the tubuloalveolar glands possessed myoepithelial cells which extended over the basal surfaces of the secretory cells and were attached to them by desmosomes. The glands were supplied by fenestrated capillaries. Periacinar and intraepithelial nerves of the glands exhibited high positive acetylcholinesterase and negative butyrocholinesterase activity. The reaction product was localized in the interval between the axolemma and the cell membranes of the secretory, myoepithelial or Schwann cells, respectively. The axon varicosities of the periacinar nerves and the intraepithelial endings contained accumulations of agranular vesicles in preparations fixed with osmic acid, formalin or permanganate solutions, signifying cholinergic nerves. The blood vessels of the nasal glands were supplied by cholinergic and adrenergic nerves.     

LFA-1 expression on exocrine glands as a potential novel marker of malignant disease.

The lymphocyte function associated antigen 1 has been found only on leukocytes and lymphoid tissues; however, the expression of lymphocyte function associated antigen 1 on nonhematopoietic cells has not been reported previously. In this study, immunohistochemical expression of lymphocyte function associated antigen 1 was examined on various tissues from 35 patients with malignant diseases and 36 patients with benign diseases including benign tumors. The expression of lymphocyte function associated antigen 1 was found on various exocrine tissues (eg, gastric glands, bronchial epithelium, alveolar epithelium, duodenal glands, bile ducts, pancreatic acini, and salivary glands) uninvolved by tumor in patients with malignant diseases. Localization of lymphocyte function associated antigen 1 was limited to the exocrine glands and differed from tissue-infiltrating leukocytes. The expression of lymphocyte function associated antigen 1 on exocrine tissues was confirmed in all 35 cases of malignant diseases that were examined. These included a wide spectrum of carcinomas and hematopoietic tumors. In contrast, none of the 36 cases with benign diseases examined expressed lymphocyte function associated antigen 1 on their exocrine glands. These results indicate a strong correlation between lymphocyte function associated antigen 1 expression on exocrine glands and malignant disease. The expression of lymphocyte function associated antigen 1 on nonhematopoietic cells was further confirmed in nonhematopoietic cell lines. Two of 19 nonhematopoietic cell lines (MKN45 and PANC-1; exocrine gland cell lines) examined expressed lymphocyte function associated antigen 1 on both cell surface and cytoplasm. These results suggested that immunohistochemically defined lymphocyte function associated antigen 1 molecules on nontumorous exocrine gland cells are a potential marker for the presence of malignant diseases.