A new look at transudation: the apocrine connection.

Transcellular trafficking in which various molecules are transported across the interior of a cell, is commonly classified as transcytosis. However, historically this term has been used synonymously with transudation. In both cases transcellular trafficking starts with the internalization of proteins or other compounds on the basal or basolateral side of a cell and continues by their transport across the interior to the apical pole (or vice versa) where they are subsequently released. This allows a cell to release products which are synthesized elsewhere. Here, we discuss the common features of both transcytosis and transudation, and that which differentiates them. It appears that transcytosis and transudation are identical in terms of vesicular import and endosomal sorting of cargo, but completely differ in the re-secretion process. Specialized epithelial cells re-release substantial quantities of the endocytosed material, and often also a great variety. Some recent studies indicate that this is achieved by non-canonical apocrine secretion rather than by the regular vesicular mechanism of exocytosis, and takes place only on the apical pole. This massive re-release of endocytosed proteins, and potentially other compounds via the apocrine mechanism should be considered as transudation, distinct from transcytosis.

Ultrasound Characteristics of the Hair Follicles and Tracts, Sebaceous Glands, Montgomery Glands, Apocrine Glands, and Arrector Pili Muscles.

OBJECTIVES: To explore the capability of very high-frequency ultrasound (US; 50-71 MHz) to detect the normal morphologic characteristics of the hair follicles and tracts, sebaceous glands, Montgomery glands, apocrine glands, and arrector pili muscles. METHODS: A retrospective study, approved by the Institutional Review Board, evaluated the normal US morphologic characteristics of the hair and adnexal structures in a database of very high-frequency US images extracted from the perilesional or contralateral healthy skin of 1117 consecutive patients who underwent US examinations for localized lesions of the skin and 10 healthy individuals from December 2017 to June 2018. These images were matched with their counterparts from the database of normal histologic images according to the corporal region. The Cohen concordance test and regional mean diameters of the hair follicles and adnexal structures were analyzed. RESULTS: The normal hair follicles and tracts, sebaceous glands, Montgomery glands, apocrine glands, and arrector pili muscles were observed on US images and matched their histological counterparts in all the corporal regions. There was significant US concordance (κ = 0.82; P = .0001) among observers. Regional mean diameters (millimeters) of the hair follicles, sebaceous glands, and apocrine glands are provided. CONCLUSIONS: The hair follicles and tracts, sebaceous glands, Montgomery glands, apocrine glands, and arrector pili muscles are detectable with very high-frequency US, including some regional and anatomic variants. Knowledge of their normal US appearances is a requisite for detecting subclinical changes, understanding the physiopathologic characteristics, and supporting the early diagnosis and management of common dermatologic diseases.

Ultrastructure and immunohistochemical characterization of proteins concerned with the secretory machinery in goat ceruminous glands.

The expression of soluble N-ethyl-maleimide sensitive fusion attachment protein receptor (SNARE) proteins in apocrine glands has not been fully elucidated. In addition to performing ultrastructural observation of the ceruminous glands in goats, our study focuses on the demonstration of ß-defensins, SNARE proteins and Rab3D in these glands with the use of immunohistochemical methods. The secretory cells were equipped with two types of vesicles, Golgi apparatus and abundant rough endoplasmic reticulum (ER). Additionally, in some of them, the characteristic concentric structures composed of rough ER were observed in their circum- and infranuclear parts. The expression of phosphorylated inositol requiring enzyme 1a was also detected. These findings may indicate their ability to produce numerous secretory proteins and the maintenance of homeostasis in the glandular cells. Furthermore, ß-defensins were demonstrated as products of the ceruminous glands. The present investigation also revealed the presence of SNARE proteins and Rab3D. It is suggested that these proteins are concerned with the secretory machinery of this gland type.

Histological, chemical and behavioural evidence of pedal communication in brown bears.

Most mammals rely upon scent for intraspecific communication. As most bear species have large home ranges and are non-territorial, scent deposit while walking could be an effective way to communicate with conspecifics. Here, we investigate the existence of pedal glands in brown bears and their role in chemical communication from a histological, biochemical and behavioural perspective. We found eccrine glands in footpads, and prominent apocrine and sebaceous glands in the interdigital, metacarpal and metatarsal skin sections. Pedal scent contained 26 compounds including carboxylic acids, important constituents of mammalian secretions. Six of these compounds were exclusive for males. Finally, we describe a specific marking gait recorded in the field, mostly performed by males. Our study supports the existence of chemical communication through pedal marking in brown bears and suggests sex-coding potential of pedal scent.

Is the eccrine gland an integral, functionally important component of the human scalp pilosebaceous unit?

The pilosebaceous unit (PSU) and the eccrine sweat gland (ESG) are classically described as completely independent skin appendages. However, careful inspection of scalp follicular units reveals that the secretory segment of the ESG spatially approximates the hair follicle in a position below the sebaceous gland and the insertion of the arrector pili muscle. Therefore, we propose here that, contrary to conventional wisdom, the PSU and the ESG should not be viewed in isolation, and may form instead, along with the arrector pili muscle and the apocrine gland (where present),one functional unit. For this, we suggest the more inclusive term of 'Hair Cluster' (HC). If confirmed, e.g. by 3D imaging techniques, the novel concept of a functional HC, whose individual components may communicate via secreted molecules and may share selected progenitor cell populations for HC repair/regeneration, has major physiological and pathological implications, which are briefly discussed.

Histochemical analyses of anti-microbial substances in canine perianal skin with special reference to glandular structures.

Circumanal glands are prominent features of the canine perianal skin, which are often located near to the sebaceous glands and apocrine glands. As the functional relevance of circumanal glands is yet unknown, we studied the localisation of sialic acids and anti-microbial substances (lysozyme, immunoglobulin A, lactoferrin, ß-defensin) in these glandular structures by lectin histochemistry and immunohistochemistry. The glands exhibited a number of sialic acids that were linked to α2-6Gal/GalNAc and α2-3Galß1-4GlcNAc. Additionally, lysozyme, lactoferrin and ß-defensin could be demonstrated in the three types of skin glands, whereas IgA was only detectable in the apocrine glands. The results of the study suggest the specific significance of the circumanal glands. Independent of a certain endocrine role, their products may mainly function as protective agents to preserve the integrity of the anal region, considering that sialic acids and anti-microbial substances are important in defence mechanisms.

The secretory clear cell of the eccrine sweat gland as the probable source of excess sweat production in hyperhidrosis.

Primary hyperhidrosis is characterized by excessive sweating in palmar, plantar and axillary body regions. Gland hypertrophy and the existence of a third type of sweat gland, the apoeccrine gland, with high fluid transporting capabilities have been suggested as possible causes. This study investigated whether sweat glands were hypertrophied in axillary hyperhidrotic patients and if mechanisms associated with fluid transport were found in all types of axillary sweat glands. The occurrence of apoeccrine sweat glands was also investigated. Axillary skin biopsies from control and hyperhidrosis patients were examined using immunohistochemistry, image analysis and immunofluorescence microscopy. Results showed that glands were not hypertrophied and that only the clear cells in the eccrine glands expressed proteins associated with fluid transport. There was no evidence of the presence of apoeccrine glands in the tissues investigated. Preliminary findings suggest the eccrine gland secretory clear cell as the main source of fluid transport in hyperhidrosis.

Human axillary apocrine glands: proteins involved in the apocrine secretory mechanism.

The apocrine secretory mechanism is a mode of secretion by which the apical part of the cell cytoplasm is pinched off, which leads to the formation of an aposome. The distinct mechanism of formation and decapitation of the aposome is not well investigated. Only few proteins are known that are involved in this secretory mechanism. We studied the human axillary apocrine gland and looked at proteins associated with cytokinesis, a process that is comparable to the pinching-off mechanism of apocrine glandular cells. By immunohistochemistry, we detected actin, myosin II, cytokeratin 7 and 19, α- and ß-tubulin, anillin, cofilin, syntaxin 2, vamp8/endobrevin and septin 2. In highly active glandular cells, these proteins are located at the base of the apical protrusion when the aposome is in the process of being released or are concentrated in the cap of the apical protrusion. These findings demonstrate new insights on apocrine secretory mechanisms and point to similarities to the terminal step of cytokinesis, which is regulated by a SNARE-mediated membrane fusion event.

A reappraisal of eyelid eccrine and apocrine hidrocystomas: microanatomic and immunohistochemical studies of 40 lesions.

PURPOSE: To establish reliable criteria for diagnosing eyelid eccrine and apocrine hidrocystomas. DESIGN: Retrospective clinicopathologic and immunohistochemical study. METHODS: Twenty-two specimens of normal portions of eyelids were evaluated to establish the distribution and microanatomy of eccrine and apocrine glands. Immunostaining for cytokeratin 7 (CK7), gross cystic disease fluid protein-15 (GCDFP-15), alpha-smooth muscle actin (α-SMA), epithelial membrane antigen (EMA), and carcinoembryonic antigen (CEA) was performed on these tissues and on 40 lesions in 33 patients diagnosed with eccrine or apocrine hidrocystomas by unaided light microscopy. RESULTS: Eccrine glands were not present in the eyelid margins, the lower half of the upper eyelid pretarsal skin, or the pretarsal lower eyelid skin. Apocrine glands were restricted to the eyelid margins and canthi where the cysts were located. GCDFP-15, CK7, and α-SMA immunoreacted with the eccrine secretory coils but not their ducts; apocrine gland secretory spirals also stained positively for these markers throughout their extended courses, but not their short terminal ducts. Positivity was found in 37 of 40 hidrocystomas for α-SMA and 19 for GCDFP-15; lesions tested for CK7 displayed positivity. CONCLUSIONS: Alpha-SMA-, CK7-, and/or GCDFP-15-positive apocrine hidrocystomas were the only type discovered in this series and arose from glandular secretory spirals within the marginal, perimarginal, or canthal skin. Three lesions did not stain for α-SMA, initially suggesting an absent myoepithelium and therefore an eccrine ductal origin; they manifested CK7 positivity, however, another characteristic of the apocrine secretory spiral but not ducts. Our findings disprove the contention that eccrine predominate over apocrine hidrocystomas in the eyelids.

Glycocomposition of the apocrine interdigital gland secretions in the fallow deer (Dama dama).

The secretions of the tubular interdigital glands were investigated by conventional (Periodic-Acid Schiff, Alcian-Blue at different pH, Low Iron Diamine and High Iron Diamine) and lectin (Con-A, UEA-I, LTA, WGA, GSA-II, GSA-IB4, SBA, PNA, ECA, DBA, MAL-II and SNA) histochemical methods in adult males and females of different age of fallow deer during the breeding season. Sialidase digestion and deacetylation pre-treatment were also employed in conjunction with lectin histochemistry. The glandular epithelium consisted of a single layer of low columnar cells with typical apical protrusions. No substantial differences of the above histochemical staining in relation to sex and age were observed. Conventional histochemical staining revealed that the interdigital glands secreted neutral glycoproteins whereas acidic glycocomponents did not seem to be present. Lectin histochemical technique allowed us to disclose a great heterogeneity of glycoproteins with N- and O-linked oligosaccharides containing alpha-d-Man/alpha-d-Glc, GlcNAc, alpha-Fuc, terminal beta-d-Gal-(1-3)-d-GalNAc, -d-Gal-(1-4)-d-GlcNAc, alpha-Gal and beta-GalNAc residues. beta-GalNAc and disaccharide beta-d-Gal-(1-3)-d-GalNAc were also found as subterminal to sialyl moieties. The lack of sexual and age-related differences in the glucidic content of the glandular secretions seems to indicate that the glycoderivatives may play only an accessory role in the production of odoriferous signals in fallow deer.

Immunolocalization of defensins and cathelicidin in human glands of Moll.

The human gland of Moll located at the margin of the eyelids is a specialized apocrine gland, the function of which is not exactly known. The presence of antimicrobial proteins was identified in this gland recently, suggesting a function in the external ocular defense barrier against pathogens. In this study, we have demonstrated beta-defensin-1, beta-defensin-2 and cathelicidin (LL-37) in the secretory endpieces of the glands of Moll using immunohistochemical methods. beta-Defensin-1, beta-defensin-2 and cathelicidin (LL-37) showed a weak to moderately intensive staining pattern. The strongest immunolocalization of beta-defensin-1 was observed in the apical protrusions of the gland, which could also be observed but to a lesser extent in the case of beta-defensin-2 and cathelicidin. In active glandular cells, a granular staining pattern could be observed. beta-Defensin-1 and beta-defensin-2 varied in staining intensities, and even within one section strongly and weakly stained cells can coexist side by side. Also cells that, according to morphological criteria, appeared to be inactive still had an apical beta-defensin-1 immunolabeling. We assume that beta-defensin-1, beta-defensin-2 and cathelicidin (LL-37) work together with other antimicrobial peptides and proteins to create a defensive barrier against microbial invasion at the ocular surface.

The absence of apoeccrine glands in the human axilla has disease pathogenetic implications, including axillary hyperhidrosis.

BACKGROUND: The existence of a third type of sweat gland in human axillary skin, the apoeccrine gland, with a capacity to produce much higher sweat output than the eccrine gland, was proposed from examination of microdissected glands. However, previous studies of axillary skin glands did not examine the entire individual glandular structure via serial sections and the markers used to identify the different glands gave conflicting results and, hence, the existence of the apoeccrine gland remains controversial. OBJECTIVES: To investigate human axillary sweat glands by serial section histology and immunofluorescence. METHODS: Human axillary sweat glands were investigated by serial sectioning of paraffin wax-embedded skin samples taken by biopsy from four male and six female volunteers (age range 20-35 years). Sections were examined by light microscopy and immunofluorescence, using antibodies to antigens reported to be markers for discriminating between eccrine and apocrine gland cells: CD15, CD44, S100 and human milk fat globulin. RESULTS: Light microscopy demonstrated that there were hair follicles and a mean +/- SD of 76 +/- 14 sweat glands cm(-2). Eccrine and apocrine glands were found to be present; however, no glands resembling the apoeccrine glands were detected. Both types of sweat gland exhibited signs of being active, with segments of the secretory coils displaying flattened cells and dilated glandular lumina; however, this dilation did not extend to obvious changes in the width of the gland. None of the eccrine glands exhibited evidence of the presence of apocrine cells or vice versa. Immunofluorescence markers were found not to be specific and did not discriminate between the different types of glands or demonstrate the presence of apoeccrine glands. CONCLUSIONS: This is the first time that serial sections of axillary skin have been examined by histology and immunofluorescence. The markers reported to discriminate between apocrine and eccrine glands were found to be nonspecific. No evidence of apoeccrine glands was found either by histology or by immunofluorescence.

Morphology of the intermandibular gland of the Lesser mouse deer, Tragulus javanicus.

The morphology of the intermandibular gland of the Lesser mouse deer (Tragulus javanicus), which plays an important function in marking area and territory and in the reproductive behaviour of the animal, was examined using immunohistochemistry, lectin histochemistry and scanning electron microscopy. The gland was composed of sebaceous and apocrine glandular material. Sebaceous glands occupied a greater area of the total gland and consisted of many large lobules with polyhedral cells having a pale cytoplasm. The sebaceous gland, being holocrine, possessed no special secretory ducts. The apocrine gland was lined by cuboid cells and the secretory products were often seen in the apical portions of the cells. Myoepithelial cells contained actin filaments lining the basal membranes of the apocrine gland and were surrounded by nerve fibres which immunostained with protein gene product 9.5. The secretion of the gland appears to be a mixture of larger amounts of lipid material from sebaceous glands, and glycoconjugates secreted by both sebaceous and apocrine glands. Lectin histochemistry detected these as galactose, N-acetyl-D-galactosamine, N-acetyl-D-glucosamine, D-mannose and D-glucose. The male gland was larger in size and contained more N-acetyl galactosamine and N-acetyl glucosamine in its secretion than the gland of the female. This implied the presence of sexual differences in secretions in the intermandibular gland of the Lesser mouse deer.

Immunohistochemical differentiation and localization analysis of sweat glands in the adult human axilla.

BACKGROUND: The classic concept of axillary glands differentiates between eccrine glands, producing abundant clear, nonodorous sweat; and apocrine glands, excreting small amounts of turbid, odorous milky sweat. A third type of sweat glands, the "apoeccrine" glands, were recently identified. To define the different types of sweat glands and their location and number, the authors carried out a prospective histologic study on adult human axillary skin, including various immunohistochemical markers. METHODS: Forty-three consecutive Caucasian, subjectively normhidrotic patients, who underwent a surgical procedure in the axilla unrelated to the axillary glands, were included in the study. For verification of normhidrosis, the gravimetric test was carried out by measuring the amount of sweat secretion per minute. Then, a 1 x 1-cm measuring piece of skin and subcutaneous tissue was excised in the apex of the axilla, divided into three samples--altogether, 129 samples--and processed for histologic examination. RESULTS: In the dermis, the authors found only very few eccrine (average, 0.3 gland/cm in only 12 percent of all patients) and apocrine glands (average, 0.1 gland/cm in only 4.7 percent of patients), and no apoeccrine glands in any patient. In the subcutaneous tissue, the mean number of glands per centimeter squared was 10 for the eccrine glands, nine for the apocrine glands, and six for the apoeccrine glands. CONCLUSIONS: In the authors' Caucasian subjects, all or most of the sweat glands were found in the subcutaneous tissue near the border to the dermis and not in the dermis. For extremely hyperfunctioning sweat glands, the authors recommend less radical surgical methods, with the preservation of skin, based on the knowledge that most glands are localized in the subcutaneous tissue.

Histological variations in myoepithelial cells and arrectores pilorum muscles among caudal, metatarsal and preorbital glands in Hokkaido sika deer (Cervus nippon yesoensis Heude, 1884).

The morphological characteristics of myoepithelial cells and arrectores pilorum muscles were investigated in caudal, metatarsal and preorbital glands of Hokkaido sika deer (Cervus nippon yesoensis Heude, 1884) using immunohistochemistry for alpha-smooth muscle actin. In the metatarsal, preorbital and general skin glands, myoepithelial cell layers continuously embraced the secretory epithelium, while in the caudal gland, discontinuous myoepithelial cell rows surrounded the apocrine tubules. There was a trend that the widths of the myoepithelial cells of the caudal and preorbital glands appeared to be thinner than those of the metatarsal and general skin glands. In the metatarsal gland, the arrectores pilorum muscles were highly developed and considerably larger than those in other skin glands.

[Unknown hepatoid glands of some species of cats and deer]. / Neizvestnye gepatoidnye zhelezy nekotorykh koshach'ikh i olen'ikh.

Our histological description of the fourth type of mammalian skin glands--hepatiod glands--allowed us to revise the obtained and published data mistaking the alveolar glands of the anal sacs in cats and the limb glands in deers as sebaceous. Large clusters of hepatiod glands were discovered in the anal sacs of the cat, lynx, and tiger, interdigital gland of elk, and the tarsal gland of reindeer. These glands secrete considerable amounts of protein to the clearance of the intercellular canaliculi and contain hydrophobic lipids. The available data substantiate revision of the data on the structure of many skin glandular organs with atypical sebaceous glands.

Structure and function of human sweat glands studied with histochemistry and cytochemistry.

The basic structure and the physiological function of human sweat glands were reviewed. Histochemical and cytochemical techniques greatly contributed the elucidation of the ionic mechanism of sweat secretion. X-ray microanalysis using freeze-dried cryosections clarified the level of Na, K, and Cl in each secretory cell of the human sweat gland. Enzyme cytochemistry, immunohistochemistry and autoradiography elucidated the localization of Na,K-ATPase. These data supported the idea that human eccrine sweat is produced by the model of N-K-2Cl cotransport. Cationic colloidal gold localizes anionic sites on histological sections. Human eccrine and apocrine sweat glands showed completely different localization and enzyme sensitivity of anionic sites studied with cationic gold. Human sweat glands have many immunohistochemical markers. Some of them are specific to apocrine sweat glands, although many of them stain both eccrine and apocrine sweat glands. Histochemical techniques, especially immunohistochemistry using a confocal laser scanning microscope and in situ hybridization, will further clarify the relationship of the structure and function in human sweat glands.

[Morphology of sweat glands]. / Morphologie des glandes sudorales.

There are two types of sweat glands: eccrine glands, which do not show cytological changes during secretion and apocrine glands, characterised by decapitation secretion, in which part of the cell is pinched off and released into the lumen. Eccrine glands play a major role in thermoregulation and electrolyte balance. They are present everywhere in the human skin and are composed of a secretory portion, an intradermal duct and an upper intraepidermal part, called acrosyringium. The acrosyringium has a unique symmetrical and helicoidal course, which length is correlated to the thickness of the epidermis. Apocrine glands are located only on genital, axillary and mammary areas, where they are always connected to a hair follicle. Their exact role in humans is unknown. A third type of intermediate sweat glands, the apoeccrine glands, was recently described in axillary areas. Sweat glands can be involved in various inflammatory processes and can lead to a large range of both benign and malignant tumors.