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Hyaline inclusions (Pseudopsammoma bodies) in meningiomas: immunocytochemical demonstration of epithel-like secretion of secretory component and immunoglobulins A and M.

Three meningotheliomatous meningiomas showed prominent formation of hyaline inclusions (pseudopsammoma bodies). Immunocytochemical examination by means of indirect immunofluorescence and PAP techniques demonstrated strong labeling of these inclusions by antisera to human secretory component (SC), immunoglobulin (Ig) A and IgM. A similar staining pattern was found in intracytoplasmic globules of a metastatic carcinoma. Hyaline structures of various types in atypical, psammomatous, and hemangiopericytic meningiomas were not stained with the antisera employed. By histochemical, immunocytochemical, and ultrastructural criteria, pseudopsammoma bodies in meningiomas are identical with intracytoplasmic inclusions of some epithelial neoplasms, especially of mammary and gastric carcinomas. Our study strongly corroborates Kepes' (1961, 1975) concept of secretory differentiation in meningiomas, and demonstrates an epithelial character at least of some meningiomas.

Adult↗

[Method of preparation and evaluation of antisera for the differential determination of secretory immunoglobulin A and free secretory component in biological fluids].

One of the pressing tasks in the study of local nonsusceptibility to infectious diseases and immunochemical analysis of the external secretion is recording of the level of various forms of the secretory IgA (SIgA) and of the secretory component (SC) in various biological fluids. Indication and measurment of the concentrations of the mentioned proteins encounter serious difficulties caused by heterogeneity of their molecular forms. It was shown that the antisera to the whole molecule of SIgA and SC are of no use. On the basis of a new method of purification of free SC and technology of preparation of monospecific antisera capable of separation of SIgA and free SC there were obtained diagnostic antisera for the quantitative recording and differentiation of various forms of IgA and SC in biological fluids. A reliable measurement of the SIgA and SC concentration in some external secretion was carried out with the aid of the mentioned preparations without any complicated chromatographic experiments.

Animals↗

[Immunohistochemical localization of keratin and secretory component in carcinoma of the uterine cervix].

Carcinoma of the uterine cervix is said to frequently show a combination of squamous epithelial and glandular epithelial characteristics. In the present study, immunohistochemical localization of keratin and secretory component (SC) was studied to clarify these characteristics of cancers of the cervix, and the following results were obtained. Demonstration of the localization of keratin and SC was useful in providing functional markers of the squamous and glandular epithelium of the cervix. In epidermoid carcinomas, the squamous epithelial character of the keratinizing carcinomas was strongest and decreased in the large cell non-keratinizing, followed by the small cell non-keratinizing carcinomas. The glandular character of these lesions decreased in the same order. Subclassification of CIS did not reveal any major changes with either kind of staining. So-called bipotential differentiation was found in 21% of the epidermoid, 53% of the adenocarcinomas and 13% of the CIS. In the clinical stages of epidermoid carcinomas, the stage I and II cases more frequently showed squamous characteristics than did the stage 0 cases.

Adenocarcinoma↗

Tubular adenoma of the human stomach. An immunohistochemical analysis of gut hormones, serotonin, carcinoembryonic antigen, secretory component, and lysozyme.

A total of 49 gastric tubular adenomas and 6 tubular adenomas with foci of adenocarcinoma from surgically resected stomachs were examined histologically and immunohistochemically for gut peptide hormones, serotonin, carcinoembryonic antigen (CEA), secretory component (SC), and lysozyme. A variety of endocrine cells were detected in tubular adenoma with mild to moderate atypia. Both the frequency and distribution density were highest for serotonin-containing EC cells, often showing hyperplasia, followed by glicentin-containing L cells, somatostatin-containing D cells and motilin-containing Mo cells in the order given. Adenoma cells with SC immunoreactivity were more dominant than those with CEA immunoreactivity. In tubular adenoma with severe atypia, endocrine cells were markedly decreased, whereas adenoma cells with CEA immunoreactivity were increased. The distribution density of lysozyme-containing cells in tubular adenoma of the intermediate zone and fundus was significantly higher than that of the antrum. In the subjacent mucosa of the adenoma, L cells and SC-positive epithelial cells were detected in 24 and 33 cases, respectively. These findings suggest that gastric tubular adenoma develops from intestinal metaplasia. In addition, gastric tubular adenoma showed a tendency to lose various intestinal markers with increase of histologic atypicality.

Adenoma↗

[Immunohistochemical localization of epithelial membrane antigen, carcinoembryonic antigen and secretory component in urinary bladder cancer].

To clarify the relationship between the immunohistochemical distribution pattern of epithelial antigens in transitional cell carcinomas and their histopathological grading and staging, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA) and secretory component (SC) were localized. Formalin-fixed paraffin-embedded sections from 55 patients with bladder carcinoma were stained by the indirect immunoperoxidase method. In normal transitional epithelium, EMA was found on the luminal side of the plasma membrane of a few surface layers, and in the cytoplasm of the superficial cells. In the lower grade and stage of transitional cell carcinoma, only the luminal surface of superficial cells was positively stained. Membrane and cytoplasmic staining of EMA was frequently found in the intermediate and basal layers of the carcinoma, and the incidence of cytoplasmic staining increased with the higher grade and stage. CEA was not detected in normal epithelium. Cytoplasmic staining of CEA was progressively more frequent in the higher grade and stage of transitional cell carcinoma. In normal epithelium SC was observed on the apical surface plasma membrane and in the cytoplasm of the superficial cells, as shown in the immunohistochemical staining for EMA. The correlation of immunohistochemical detection of SC with the grade or stage was not as good as the correlations for EMA or CEA. These findings suggest that immunohistochemical examination for EMA, CEA and SC in bladder carcinoma could provide valuable information for grading or staging in pathological diagnosis.

Carcinoembryonic Antigen↗

Lack of relation between expression of HLA-DR and secretory component (SC) in follicle-associated epithelium of human Peyer's patches.

Follicle-associated epithelium (FAE) of normal human Peyer's patches (PP) was studied with regard to expression of HLA-DR determinants and secretory component (SC); the latter acts as a receptor for polymeric immunoglobulins (pIg). Putative M cells were identified in FAE by lack of a brush border with alkaline phosphatase. These cells were virtually negative for HLA-DR whereas the remaining FAE was strongly positive like villous epithelium. Conversely, the complete FAE showed no SC expression and was negative for IgA. These findings suggested that the FAE (including the M cells) does not participate in SC-mediated transport of pIgA, which in the gut mainly takes place through columnar crypt cells. The FAE (excepting the M cells) may be involved in an MHC class II-restricted antigen-presenting function as recently suggested for villous epithelium. The role of M cells may hence be limited to uptake and transport of luminal antigens.

Alkaline Phosphatase↗

Immunoelectron microscopic study on IgA, secretory component and complement component C3 in the liver of children undergoing total parenteral nutrition through neonatal period.

To study the mechanism of the intrahepatic cholestasis observed during total parenteral nutrition (TPN) in neonates, we examined the localization of IgA, secretory component (SC) and complement component C3 (C3) in the liver in 4 patients by light and electron microscopic immunohistochemistry. In the patients who received TPN for 1 month, IgA- and SC-positive cholestasis was limited to bile canaliculi, but the integrity of both the canalicular wall and intercellular tight junction was maintained. These findings suggest that obstruction in the biliary tract develops at the canalis of Hering, causing reflux of IgA and SC into the bile canaliculi. When the duration of TPN extended beyond 6 months, the cholestasis in bile canaliculi progressed further, and degeneration of hepatocytes became more marked. Bile retained in hepatocytes occasionally contained IgA and SC. IgA- and SC-positive cholestasis also developed in the interlobular bile ducts, where no cholestasis had been observed 1 month after the beginning of TPN. SC production and SC-mediated transport of IgA, which are important functions of bile duct epithelial cells in the local immune mechanism, were impaired in association with the injury of those cells. C3 was localized not only in the hepatocellular organelles where C3 is normally observed, but also in the lumen of dilated bile canaliculi, suggesting that C3 is released from hepatocytes into bile in neonates receiving TPN and that C3 may be involved in some local immune mechanism of biliary system.

Complement C3↗

Urethral glands of the male mouse contain secretory component and immunoglobulin A plasma cells and are targets of testosterone.

The occurrence and possible functions of mucosal immunity in the male urogenital tract have not been extensively investigated. In this study we used immunolabeling to localize secretory component (SC) and immunoglobulin (Ig) A in the urogenital tract of the male mouse. SC was located in the ventral prostate, while SC and IgA plasma cells were both detected in the urethral glands in the pelvic and bulbous portions of the urethra. SC and IgA were not observed elsewhere in the urogenital tract. We also examined the ventral prostate and urethral glands of sham-castrated, oil-treated castrated, and testosterone-treated castrated mice. There was a striking reduction in the size of the ventral prostate and urethral glands in oil-treated castrates compared to the other two groups, based on gross and histological morphology. Morphometric analysis showed that the cell and nuclear sizes of the urethral gland acinar cells were reduced after castration and restored to normal size by testosterone treatment. Androgen receptors (AR) were localized in the nuclei of urethral gland cells by immunocytochemistry using anti-AR antibodies. Labeling of SC and IgA plasma cells was similar in the urethral glands and ventral prostates of sham- and testosterone-treated castrates, but was reduced or absent at these sites in oil-treated castrates. These studies show that the ventral prostate and urethral glands may be sites for secretory immunity in the male murine urogenital tract, and that the urethral glands are targets for testosterone.

Animals↗

Immunoglobulins and secretory component in the external secretions of foals with combined immunodeficiency.

Nasal washings and tears were collected from seven Arabian foals with combined immunodeficiency and nine normal foals. The major immunoglobulin in the external secretions of normal foals over 2 months of age was secretory immunoglobulin A, whereas foals with combined immunodeficiency lacked this immunoglobulin. The external secretions of both normal and immunodeficient foals contained free secretory component at birth.

Age Factors↗

Secretory component (SC): preferential binding to heavy (greater than 11S) IgA polymers and IgM in serum, in contrast to predominance of 11S and free SC forms in secretions.

The origin and molecular form(s) of the small amounts of secretory component (SC) found in serum are but poorly known. Using sensitive immunoradiometric assays for SC, we studied its molecular distribution after ultracentrifugation of native sera containing various proportions of IgA and IgM, with SC levels (sIgA equivalents) ranging from 4 to 25 micrograms/ml. Large proportions of SC were found bound to IgM and IgA polymers heavier than the classical 11S sIgA, in contrast to saliva and bile where SC was found mainly in the 11S region and in the free form. A comparative study of the ultracentrifugal distribution of labelled free SC, incubated in vitro with sera containing various proportions of IgA and IgM, yielded similar results, indicating a direct relationship between the proportion of IgM-bound SC and the IgM concentration. Free SC in serum was only found in the in vitro experiments. The data suggest that the epithelial cells synthesizing SC not only release (secrete?) SC as pre-assembled SC-Ig complexes in lymph or plasma, but also directly release some SC in free form.

Bile↗

In vivo response of secretory component in the rat uterus to antigen, IFN-gamma, and estradiol.

Intrauterine immunization of ovariectomized rats with SRBC is known to elicit pronounced IgA and IgG antibody responses in uterine secretions of immunized uteri. To determine whether secretory component (SC), the receptor for transporting polymeric IgA from tissues to mucosal surfaces, was also influenced by Ag, ovariectomized rats were immunized and boosted by placing SRBC into the lumena of individual uterine horns. In response to Ag, the levels of polymeric IgA, as well as free SC and SC bound to polymeric IgA, increased in uterine secretions. When ovariectomized animals were treated with estradiol, a fivefold increase in SC levels was observed in the immunized horns, indicating that a hormone response is superimposed on the Ag-induced stimulation of uterine SC. To determine whether IFN-gamma influences the presence of SC in uterine secretions, IFN-gamma was placed in the uterine lumena of ovariectomized nonimmunized rats. When uterine secretions were analyzed, significantly higher levels of SC were found in IFN-gamma-exposed uteri than were present in saline treated control animals. In contrast, intrauterine instillation of IFN-gamma had no effect on the levels of IgA in uterine secretions. This response was specific for IFN-gamma in that IFN-alpha/beta had no effect on uterine SC or IgA levels. These results indicate that intrauterine instillation of Ag, in addition to evoking pronounced antibody responses, stimulates the production of SC, which may be responsible for the transport of polymeric IgA from tissue to uterine secretions. Furthermore, they indicate that IFN-gamma placed in the uterine lumen stimulates SC production and suggest that the uterine SC response to Ag may be mediated by the action of IFN-gamma on uterine epithelial cells.

Animals↗

Rapid selection of cultured cells with increased expression of a membrane marker (secretory component).

This study showed how immunomagnetic monodisperse microspheres (Dynabeads) can be used for rapid selection of stable and homogeneous sublines of cancer cells. The beads were activated with antibody to a specific surface membrane marker. We used a monoclonal antibody (MAb) to human secretory component (SC), the epithelial receptor for polymeric immunoglobulins (pIg). A relatively low number of particles favored rosetting of strongly positive cells. SC-expressing cells were isolated within 30 min from a colonic carcinoma cell line (HT-29.E10). After 13 months of continuous culture the selected cells had a 15 times higher cellular content and a 10 times higher secretory rate of SC than parallel cultures of the original cell line. Immunomagnetic microspheres can be recommended in experimental cancer research, e.g., in order to minimize cellular heterogeneity and to isolate cells with particular surface membrane phenotypes in differentiation studies. The selection method is rapid and simple, and eliminates laborious test systems for conventional subclone screening.

Animals↗

Epithelial expression of HLA, secretory component (poly-Ig receptor), and adhesion molecules in the human alimentary tract.

Epithelial HLA class II is differentially expressed (DR >> DP) only after birth in salivary glands and small intestinal mucosa, in contrast to class I determinants and secretory component (SC) which appear early in gestation. However, there is a brisk postnatal increase in SC expression along with the class II induction, suggesting stimulation by cytokines from activated immune cells. T lymphocytes remain quite scanty in postnatal salivary glands, and the striking SC and class II expression might reflect a synergistic effect of IFN-gamma and TFN-alpha on immature epithelial cells. Enhanced epithelial expression of both SC and class II in salivary glands from sudden infant death victims could be the effect of immunostimulation caused by an infectious agent. Strikingly upregulated SC and epithelial class II expression (DR > DP > DQ) is seen in various inflammatory lesions such as obstructive sialadenitis, Sjögren's syndrome, chronic gastritis, and celiac disease. IFN-gamma and TNF-alpha are most likely involved as the expression patterns can be reproduced with these cytokines in vitro on colonic epithelial cell lines. However, these molecules of the Ig supergene family do not show a selective response in epithelia of inflammatory lesions because increased expression is also seen for lysozyme, lactoferrin and some other proteins. ICAM-1 can be upregulated on epithelial cells by various cytokines in vitro although the situation remains uncertain in mucosal inflammation. The expression pattern in IBD is complicated by dysplastic epithelial changes leading to reduced SC levels which may thus, in turn, jeopardize the poly-Ig transport mechanism. Epithelial class II molecules appear to have antigen-presenting properties, but the immunopathologic role of their increased expression in inflammatory disease in terms of induction of autoimmunity and/or abrogation of oral tolerance is a matter of continuing dispute.

Animals↗

In vitro synthesis of immunoglobulins, secretory component, complement and lysozyme by human gastrointestinal tissues. I. Normal tissues.

An in vitro culture technique has been used to demonstrate synthesis of proteins by human gastrointestinal tissues cultured in vitro. Histologically normal tissues were obtained endoscopically and surgically. IgA and secretory component (SC) were produced in all sites, but the relative intensity of IgA synthesis and SC synthesis varied. In stomach and small intestine the intensity of IgA synthesis was greater than that of SC, but in large bowel mucosa, there appeared to be an excess of SC synthesis. Synthesis of IgG and IgM was also found in all sites. Complement proteins were produced by some of the intestinal biopsies, and by parotid gland. Lysozyme was synthesized by parotid gland and by gastric mucosa, and to a lesser extent in small intestine, and rarely in large intestine. The results suggest that in addition to the local mucosal IgA system the local production of other immunoglobulins, as well as non-immunoglobulin humoral defence factors, may be important host defences of the normal gastrointestinal tract.

Complement C3↗

Estradiol regulation of secretory component: expression by rat uterine epithelial cells.

Sex hormones are known to play an important role in the regulation of mucosal immunity in the female reproductive tract. The purpose of this study was to examine the effect of estradiol (E2) on secretory component (SC) expression by epithelial cells in the rat uterus and to determine whether SC mRNA is present in uterine tissues and is under hormonal control. When ovariectomized rats treated with E2 for 3 days and sacrificed 12 h after the last injection, expression of SC on luminal and glandular epithelial cells, as determined by immunohistochemistry, was elevated when compared to control animals. To determine whether E2 regulation of SC involves mRNA synthesis, uterine RNA was extracted and analyzed by Northern blot. These experiments demonstrated that SC RNA is present in uteri from intact rats and markedly increased when ovariectomized animals are treated with E2. In other studies, uterine epithelial cells from adult rats were isolated and grown on permeable membranes for 5 to 10 days. Under these conditions, isolated epithelial cells grow to confluence, form tight junctions, and preferentially secrete SC into the apical medium. These studies identify epithelial cells as a key target cell in the uterus for the regulation of mucosal immunity by E2, which we postulate will play an important role in studies to prevent and/or control the spread of sexually transmitted diseases.

Animals↗

Secretory component as the mucosal transport receptor: separation of physicochemically analogous human IgA fractions with different receptor-binding capacities.

This paper describes the separation and characterization of several IgA fractions from the same human monoclonal source, based on their ability to bind secretory component (SC). The study was undertaken to elucidate features of the immunoglobulin-binding site for SC, and to examine the dependence of mucosal transport on IgA-SC interaction. Enrichment or depletion of SC-binding activity was accomplished on an affinity adsorbant made with SC from human colostral whey. The affinity-purified human IgA fractions contained IgA polymers and were 77% active in rebinding to the adsorbant; this activity was diminished significantly by direct radioiodination. The non-adherent IgA fractions contained both polymer and monomer, and were only 8% active in rebinding to the adsorbant. When the polymer and monomer components were separated from each other, the non-adherent polymer was found to resemble the affinity-purified fraction by all criteria examined including J-chain content, except that the SC-binding capacity was greater than five-fold lower. These findings have two implications for the SC-binding site on human IgA: first, the presence of J-chain is insufficient to bestow IgA with SC-binding activity; second, a critical tyrosine participates in maintaining the SC-binding region, possibly on the IgA heavy chain. The relationship between SC binding and mucosal transport was tested in the rat hepatobiliary model. All radiolabeled human IgA fractions were captured rapidly from blood by the rat liver, but only the SC-binding fractions underwent substantial intact transport to bile (greater than 70% of the injected dose). Even though a nominal proportion of the SC-non-adherent IgA appeared in bile (4-15% of the dose), most IgA in these fractions was rapidly degraded within the liver. Thus, only a small amount of monomeric and polymeric IgA can use alternative receptors to get to bile by diversion from the degradative pathway. Polymeric IgA can undergo efficient transport across the cell, strictly conditional on a high binding capacity for SC. This demonstrates that membrane SC is the receptor conferring specificity on the mucosal-transport pathway.

Animals↗

Alterations in polymeric immunoglobulin receptor expression and secretory component levels in bladder carcinoma.

To assess the capacity of transitional cells to synthesize the release polymeric immunoglobulin receptor (pIg-R) in bladder carcinoma, we studied the localization of pIg-R in normal and tumor tissues and measured the levels of secretory component (SC) either in the free form or bound to Ig (S-IgA, S-IgM) in the serum and urine of 56 patients with transitional-cell carcinoma (TCC) of the bladder. In the normal bladder mucosa, pIg-R was localized in the cytoplasm and plasma membranes of the superficial cells and on all epithelial cell membranes. In TCC cases, 65% of those studied expressed pIg-R. A marked heterogeneity in pIg-R staining was observed in some tumors. Although a better expression of pIg-R in tumors with a well-preserved epithelial architecture was observed, no correlation was found between pIg-R expression and the grade or stage of the tumors in the patients under study. Three groups were established: (1) in TCC with no complications, serum levels of free SC and S-IgA were significantly increased; (2) in TCC with urinary infections (UI), serum levels of free SC and S-IgA were significantly higher than control values but lay within the same range observed in TCC with no complications and rates of urinary excretion of SC were significantly higher than those in normal subjects; (3) in TCC without UI but with hepatic disorders [high gamma-glutamyl transferase (GGT) activity], there was a correlation between serum S-IgA levels and GGT activity (r = 0.5, P less than 0.005) and serum SC levels were significantly higher than those observed in the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗

Secretory component as the receptor for polymeric IgA on rat hepatocytes.

Rat hepatocytes in short-term monolayer cultures bound radiolabeled polymeric rat IgA but not IgG. The binding of 125I-IgA was inhibited equally well by unlabeled polymeric IgA and by antiserum to rat secretory component (SC). The antibody to SC, after specific purification and radiolabeling, was bound to hepatocytes as effectively as the IgA. These results indicate that SC acts as the receptor for polymeric IgA on rat hepatocytes as it does on human gut epithelia, and that the transport of IgA from blood to bile in rats across the liver is analogous to that of IgA across human enterocytes.

Animals↗