An apocrine mechanism delivers a fully immunocompetent exocrine secretion.

Apocrine secretion is a recently discovered widespread non-canonical and non-vesicular secretory mechanism whose regulation and purpose is only partly defined. Here, we demonstrate that apocrine secretion in the prepupal salivary glands (SGs) of Drosophila provides the sole source of immune-competent and defense-response proteins to the exuvial fluid that lies between the metamorphosing pupae and its pupal case. Genetic ablation of its delivery from the prepupal SGs to the exuvial fluid decreases the survival of pupae to microbial challenges, and the isolated apocrine secretion has strong antimicrobial effects in "agar-plate" tests. Thus, apocrine secretion provides an essential first line of defense against exogenously born infection and represents a highly specialized cellular mechanism for delivering components of innate immunity at the interface between an organism and its external environment.

Pathophysiology of hidradenitis suppurativa: An update.

The pathogenesis of hidradenitis suppurativa (HS) or acne inversa is not completely understood. Recent research has led to greater insight into the mechanisms involved in the disease. The primary defect in HS pathophysiology rests with the hair follicle. Follicular occlusion, followed by follicular rupture, and a foreign body-type immune response are necessary conditions for the development of clinical HS. A specific genetic signature and environmental factors, such as cigarette smoking, microbial colonization, and adiposity, all contribute to the HS phenotype. Translational research focused on the inflammatory mechanisms involved in HS is needed to develop novel therapeutic options for this debilitating disease.

Immunocytochemical localization of lysozyme and beta-defensin in the apocrine glands of the equine scrotum.

The present study revealed in detail the subcellular localization of lysozyme and beta-defensin in the apocrine glands of the equine scrotal skin, a specific body region. The apocrine glandular cells were equipped with a varying number of secretory granules, a well-developed Golgi apparatus and abundant cisternae of the rough endoplasmic reticulum within their cytoplasm. In these cells, reactive gold particles representing lysozyme were detectable in the secretory granules as well as the Golgi apparatus and elements of the rough endoplasmic reticulum. Additionally, the antimicrobial peptide group of beta-defensin was also localized in the above-mentioned ultrastructures of the secretory cells. The presence and secretion of such substances that may serve as a non-specific defense against microorganisms are suggestive of the protective effect of the secretory production elaborated by the apocrine glands.

Human ceruminous gland: ultrastructure and histochemical analysis of antimicrobial and cytoskeletal components.

The ceruminous glands in the skin of the human external auditory canal are modified apocrine glands, which, together with sebaceous glands, produce the cerumen, the ear wax. Cerumen plays an important role in the protection of the ear canal against physical damage and microbial invasion. We studied the morphology of the glandular cells by light and electronmicroscopy. Antimicrobial and cytoskeletal components of the ceruminous glands were investigated by immunohistochemical methods. Numerous antimicrobial proteins and peptides are present in the ceruminous glandular cells: beta-defensin-1, beta-defensin-2, cathelicidin, lysozyme, lactoferrin, MUC1, secretory component of IgA. These data indicate a crucial role in the innate host defense against diverse pathogens. The apocrine secretion mechanism is a special mode of secretion by which the apical part of the cell cytoplasm surrounded by a membrane is pinched off. We could show that the presence of actin filaments, CK 19 and CK 7, seems to play a role in the pinching-off mechanism. Finally, we showed the secretion of lipid vesicles from the ceruminous gland. We could extend the number of detected antimicrobial peptides and proteins in human ceruminous glandular cells that protect the surface of the external auditory meatus. In addition, we detected proteins involved in the apocrine secretion mode of the ceruminous gland.

Apocrine glands in the eyelid of primates contribute to the ocular host defense.

Apocrine glands of Moll are regular components of primate eyelids. We studied the distribution and localization of these glands in three different primate species, the common marmoset, the rhesus monkey, and the hamadryas baboon. In addition, we tested the primate glands of Moll with antibodies against antimicrobial proteins, cytoskeletal proteins and the androgen receptor. The glands of Moll differ in abundance and distribution in different monkeys. In the common marmoset, a representative of the New World monkeys, Platyrrhini, the apocrine glands are frequently found at the lid margin and in the overlying epidermis of the lid. In the rhesus monkey and the hamadryas baboon, representatives of Old World monkeys, Catarrhini, apocrine glands are rarer and located predominantly at the margin of the lid. The immunohistochemical analysis indicates the presence of a variety of antimicrobial proteins, e.g. lysozyme, beta-defensin-2, adrenomedullin, lactoferrin, and IgA, in these glands. Interestingly, there are basically no androgen receptors in the nuclei of apocrine glands at the lid margin in all three monkey species. In the common marmoset, however, androgen receptors are found in apocrine glands of the overlying epidermis of the lid. We speculate that the glands of Moll are derived from apocrine glands as found in the skin of the entire body in New World monkeys which developed at the lid margins of higher primates and humans into specialized glands secreting agents of host defense in the eye.

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.

Identification and immunohistochemical localization of protein precursors to human axillary odors in apocrine glands and secretions.

OBJECTIVES: To determine the cellular localization in male and female axillary tissue for apocrine secretion odor-binding proteins 1 (ASOB1) and 2 (ASOB2) and the electrophoretic pattern of female apocrine proteins and to begin characterization of the ASOB1 protein. DESIGN: Immunohistochemical techniques were used with biopsy samples from axillary tissue of male and female subjects. Immunological techniques and microsequencing were used to characterize several of the proteins in male and female apocrine secretions. SETTING: A university medical center. PARTICIPANTS: Healthy male and female volunteers who donated apocrine secretions and/or axillary tissue. RESULTS: Specific immunoreactivity was localized only to the apocrine glands in both sexes. Furthermore, only preabsorption with a mixed apocrine secretion sample eliminated all immunoreactivity. The electrophoretic pattern of proteins in female apocrine secretions is similar to that in male secretions. Western blotting of the separated proteins from female samples using serum samples containing antibodies to ASOB1 and ASOB2 yielded identical results to those found with separated proteins from male samples. Partial sequence data obtained from the N-terminus of ASOB1 suggested that it shares homology with the alpha-chain of apolipoprotein J (Apo J). Apocrine secretion odor-binding protein 1 is not immunologically similar to ApoJ, but 2 other apocrine secretion proteins are. CONCLUSIONS: Male and female subjects appear to have the same glycoprotein carriers for (E)-3-methyl-2-hexenoic acid localized to the apocrine glands. The N-terminal sequence for ASOB1 may be homologous to Apo J, but it is not immunologically similar to it. However, 2 other proteins in the apocrine secretion appear to be the monomer and dimer forms of Apo J.

CD44 standard and variant isoform expression in normal human skin appendages and epidermis.

CD44 isoforms have been implicated in tumor progression and metastasis formation. This study presents a thorough immunohistochemical analysis of CD44 standard and isoform expression in normal human skin appendages and epidermis applying monoclonal antibodies against CD44s, CD44v3, -v4, -v5, -v6, and -v9. An improved immunohistochemical protocol with microwave-based antigen retrieval in paraffin sections and heavy metal amplification of the diaminobenzidine reaction product provided enhanced resolution and sensitivity as compared to studies on frozen sections. The hair follicle, the seborrheic and eccrine sweat glands were strongly positive for all CD44 isoforms studied. In the latter, the clear cells but not the dark (intercalated) cells were positive. the sudoriferous ducts adjacent to the glands were weakly positive for all CD44 isoforms and strongly positive near the skin surface. In the apocrine glands, the basal cells showed only a moderate positivity. The myoepithelial cells expressed only CD44s. In the epidermis, all CD44 isoforms were detectable, with strongest CD44 immunostaining in the lower third of the stratum spinosum and weaker staining in the stratum basale and the upper two-thirds of the stratum granulosum. The stratum granulosum and corneum were unreactive. Thus, a regional and cell type-specific CD44 expression was revealed.

Distribution of complement regulators (CD46, CD55 and CD59) in skin appendages, and in benign and malignant skin neoplasms.

Immunohistochemical studies were performed to establish the distribution of membrane cofactor protein (MCP; CD46), decay-accelerating (DAF; CD55) and homologous restriction factor (HRF20; CD59), in normal skin appendages, and in benign and malignant skin neoplasms. At least two of these regulators were detected on normal eccrine glands, apocrine glands and sebaceous glands. They were also found in cellular naevi (CN), seborrhoeic keratoses (SK), basal cell carcinoma (BCC), Bowen's disease (BD), squamous cell carcinoma (SCC) and Paget's disease (PD). Although there were slight differences in their distribution, these regulators were found in all the cells examined, indicating that they are essential factors in human skin as well as other organs, and in neoplasms, in preventing autologous complement attack.

Distribution of CA 125 in embryonic tissues and adult derivatives of the fetal periderm.

New murine monoclonal antibodies to a partially purified CA 125 antigen were developed and identified as M 2 and M 11. With immunohistochemical techniques, these new antibodies and OC 125 antibody were used to search for CA 125 in embryonic tissues and adult apocrine sweat glands and mammary glands. The embryonic skin, the periderm, expressed CA 125 antigen and its adult derivatives, the mammary glands and apocrine sweat glands, expressed CA 125 while in the active state of secretion. In a 6-week-old formalin-fixed and paraffin-embedded ectopic embryo specimen, antibodies M 2 and M 11 recognized CA 125 in the periderm, the notochord, the myocardium, the pericardium, the gastroenteric tract, enteric duct remnants in the umbilical cord (vitelline and allantoic ducts), the mesonephric duct, and the amnion. OC 125 staining of these formalin-fixed specimens was either very faint or absent. In a formalin-fixed and paraffin-embedded specimen of apocrine sweat glands from the axilla, antibodies M 2 and M 11 detected CA 125 antigen intracellularly in the secretory cells. Again no staining was observed with OC 125 antibody. In a frozen and acetone-fixed specimen of lactating mammary glands, antibodies M 2 and OC 125 detected CA 125 antigen intraductally. Colostrum and milk collected from 25 mothers at various stages post partum had mean CA 125 levels of 34,213 U/ml in colostrum, 1469 U/ml at 3 to 7 days, and 105 U/ml at 5 to 26 weeks.

Immunohistochemical staining of normal sweat glands.

Sweat glands from normal skin obtained at autopsy or as routine biopsies were examined using a panel of immunoperoxidase-linked antibodies. The results indicate that such a panel of antibodies defines all known functional regions of the eccrine sweat gland and provides a reliable distinction from all other skin elements.

HNK-I antibody reacts with peripheral nerves and sweat glands in the skin.

The distribution of Leu-7 antigen was investigated using immunoperoxidase staining technique. It was found that HNK-I monoclonal antibody reacted with peripheral nerves and sweat glands (both apocrine and eccrine) of the skin. HNK-I antibody is a new marker for them, and may help to elucidate the nature of some skin tumours.

Expression of differentiation antigens in benign sweat gland tumours.

Fifty benign sweat gland tumours were studied for the expression of carcinoembryonic antigen (CEA) and apocrine epithelial antigen (AEA), using immunohistochemical methods. CEA was found in thirty-two and AEA in thirty-three neoplasms. Both antigens were located in the epithelium of the luminal structures and in the intraluminar material and CEA was occasionally found also in proliferating cells. Co-expression of CEA and AEA occurred frequently in cases of syringoma, syringocystadenoma papilliferum, hidradenoma papilliferum, eccrine spiradenoma and clear cell hidradenoma. AEA was seen also in tumours showing eccrine differentiation, even though it is not present in normal eccrine sweat ducts.

Distribution of major histocompatibility antigens in normal skin.

The distribution of major histocompatibility antigens HLA-A,B,C (HLA), beta 2-microglobulin (beta 2m), and Ia-like antigens (HLA-DR; Ia) in normal skin was studied in frozen tissue sections by a four-step immunoperoxidase method and an avidin-biotin method employing monoclonal antibodies. HLA and beta 2m were present on the basal and spinous keratinocytes of the epidermis, on the outer root sheath epithelium in the infundibulum of the hair follicle, and on the excretory sebaceous duct epithelium. Ia-positive dendritic cells were found in the epidermis and hair follicles, but they were more frequent in the infundibulum and isthmus of the hair follicle than in its inferior portion or in the epidermis. In the straight eccrine duct, HLA and beta 2m-positivity was most striking in its lower portion. In the superficial duct, there was a less intense staining using the four-step procedure, but when an avidin-biotin method was used, the difference was less apparent. In contrast, the acrosyringial epithelium was markedly Ia-positive with decreasing intensity of staining as the duct penetrated the dermis. No HLA or Ia antigens were identified in eccrine glands and apocrine glands. Eccrine glands were slightly beta 2m-positive. HLA and beta 2m were uniformly present in non-dilated and dilated intradermal apocrine ducts.

Host-defense mechanisms in hidradenitis suppurativa.

Host-defense mechanisms were studied in seven patients with active hidradenitis suppurativa (HS). Granulocyte phagocytic function was measured by ingestion of Staphylococcus aureus labeled with radioactive carbon 14 and intracellular killing was determined by bactericidal pour plate method. Chemotaxis was measured by radioactive counting of sodium chromate Cr 51 granulocytes migrating in modified Boyden chambers. Granulocyte adherence was estimated in vitro by filtering blood samples through nylon fiber columns. Cell-mediated immunity was measured by intradermal delayed hypersensitivity responses to Candida, mumps. streptokinase/streptodornase, and purified protein derivative antigens. No abnormality was demonstrated in any granulocyte or cell-mediated immune function tests. Moreover, all patients had normal immunoglobulin levels and elevated total hemolytic complement. Therefore, we conclude that HS is a localized chronic infection of apocrine glands without a generalized defect in host defense.