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PubMed1976

Naturally occurring polymers of IgA lacking J chain.

Two of twenty IgA myeloma proteins studied were found to lack J chain. Both IgA proteins contained dimers and higher polymers (trimers, tetramers, pentamers) in proportions similar to those found in most classical 'J-positive' proteins. Both the 'J-negative' proteins contained bound albumin and alpha-1 antitrypsin (alpha1AT),and reduction with mercaptoethylamine caused a release of albumin and alpha1AT concomitant with depolymerization of the higher polymers of IgA. These proteins formed complexes with secretory component (SC) in vitro, indicating that the presence of J chain is not a requirement for SC binding.

Binding Sites↗
PubMed2003

Intracellular accumulation of pIgA-R and regulators of transcytotic trafficking in cholestatic rat hepatocytes.

Bile duct ligation (BDL) impairs basolateral-to-apical transcytosis in hepatocytes, causing accumulation of transcytotic carriers for the polymeric IgA receptor (pIgA-R) and redistribution of secretory component (SC) from bile to blood. To gain insight into the mechanisms regulating transcytosis and the pathophysiology of cholestasis, we investigated nascent protein trafficking in control and BDL livers using cell fractionation in the context of in vivo pulse-chase experiments and immunoblot analysis. Control and cholestatic hepatocytes trafficked [35S]-labeled serum proteins and the pIgA-R along the secretory pathway with identical kinetics. However, BDL impaired transcytosis, causing (1) accumulation of the pIgA-R, rab3D, rab11a, and other candidate regulators of apical-directed secretion in a crude vesicle carrier fraction (CVCF) enriched in transcytotic carriers; (2) slow delivery of [35S]-labeled SC to bile; and (3) paracellular reflux of SC from bile to blood. In conclusion, these data indicate that the secretory and transcytotic pathways remain polarized in cholestatic hepatocytes and suggest that the pIgA-R traffics through postendosomal rab3D-, rab11a-, and syntaxin 2-associated compartments, implicating these proteins in the regulation of transcytosis.

Animals↗
PubMed1986

Distribution and processing of the polymeric immunoglobulin receptor in the rat hepatocyte: morphological and biochemical characterization of subcellular fractions.

The transepithelial transport of polymeric immunoglobulins is an essential process in the mucosal immune system. Transport across the epithelial cells of mucous or exocrine glands is affected by an integral membrane glycoprotein receptor known as membrane secretory component (SCm) or as polymeric immunoglobulin receptor (pIgR). This receptor binds polymeric immunoglobulins at the basolateral cell surface and mediates their transcellular translocation and their release from the apical plasma membrane into external secretions. Release depends on cleavage of the membrane-anchoring domain of the receptor, resulting in liberation of polymeric immunoglobulin bound to the ectoplasmic domain of the receptor (secreted SC or SCs) into extracellular secretions. Using a monoclonal antibody directed against the cytoplasmic tail of the receptor and a polyclonal antibody directed against the secreted ectoplasmic domain, we have combined cell fractionation and Western blotting techniques to examine the fate of these receptor domains in the hepatocyte. In this study, we characterize biochemically and morphologically the various subcellular components separated by our fractionation scheme, and correlate this with biochemical analysis of the receptor in each fraction.

Animals↗
PubMedDate not supplied

Monensin and bile protein secretion. A tool to investigate hepatocyte intracellular vesicular polarity.

Bile derived from monensin treated bile-fistula rats was analysed by SDS-polyacrylamide gels. Differences in proteins were observed for bands presumptively corresponding to transferrin, secretory-IgA and free secretory components after treatment with the ionophore. The results show that the secretion of proteins in bile is differentiated and asyncronous, confirming a polarity of the hepatocyte subcellular compartments.

Animals↗
PubMed1984

Immunohistochemical characterization of functional markers in human minor salivary gland tumors.

The distribution of carcinoembryonic antigen (CEA), secretory component (SC), immunoglobulin A (IgA), immunoglobulin M (IgM), J-chain, and lysozyme in tumors of minor salivary glands was investigated using an immunoperoxidase method. Although CEA was demonstrated in both benign and malignant tumors, its distribution was relatively more common and with increased staining intensity in malignant tissues. In pleomorphic adenomas, the distribution of SC was similar to that of IgA and J-chain, suggesting the presence of secretory IgA in the epithelial cells. However, some neoplastic epithelial cells contained SC but not IgA and J-chain. No IgM was detected in such cells. Lysozyme could be demonstrated only in pleomorphic adenomas. Mucoepidermoid tumors and adenoidcystic carcinomas were negative for lysozyme. These findings suggest that some neoplastic ductal epithelial cells of pleomorphic adenomas retain functional characteristics of normal epithelial cells.

Adenoma, Pleomorphic↗
PubMed1984

Immunofluorescence study of secretory epithelial markers in pleomorphic adenomas.

Amylase (Am), lactoferrin (Lf), lysozyme (Ly), secretory component (SC), epithelial IgA, and epithelial IgM were traced by paired immunofluorescence staining in ethanol-fixed specimens from 15 pleomorphic adenomas of the parotid gland. Epithelial elements positive for some of the markers were detected in a variable number of the specimens (Am, 0; Lf, 11, Ly, 2; CEA, 6; SC, 11; IgA, 9; and IgM, 6); their expression seemed to depend on a certain degree of glandular differentiation. Variable co-expression of secretory epithelial markers probably reflected different degrees of differentiation, indicating that clonal diversification may explain the histological complexity of pleomorphic adenomas. The most consistent expression (in almost 75% of the specimens) shown by Lf and SC might further reflect histogenetic relationship to intercalated ducts in which these antigens are normally found in largest amounts.

Adenoma, Pleomorphic↗
PubMed1984

Isoelectric focusing of human IgA and secretory proteins using thin layer agarose gels and nitrocellulose capillary blotting.

A simple, rapid and economical method for focusing human immunoglobulin A in low electroendosmosis agarose is described. IgA preparations isolated from serum and secretions were focused with high resolution in thin layer gels. Serum and milk proteins were transferred to nitrocellulose sheets by capillary blotting and the spectrotype of total IgA determined with radiolabeled anti-human IgA antibodies. These studies indicated that the spectrotype of human IgA extends between the pH range 4.3-6.85. The spectrotypes of free secretory component and alpha-1 antitrypsin released from an IgA myeloma protein were determined by a similar technique. These methods should prove useful in determining the diversity of IgA antibodies whether or not the starting material is pure.

Collodion↗
PubMed1999

[Helicobacter pylori infection and histological types of gastric cancer].

The relationship between Helicobacter pylori (H. pylori) infection and gastric cancer was evaluated clinicopathologically by histological types of gastric cancer (intestinal or diffuse type). Histological findings of resected stomach tissues and serum anti-H. pylori IgG antibody titers obtained in patients with early gastric cancer revealed H. pylori infection and associated inflammatory changes in all cases, irrespective of histological types of cancer, and suggested that diffuse type cancer occurs in the mucosa with marked inflammation at a relatively early stage of H. pylori infection, while intestinal type cancer occurs at a relatively late stage of infection in parallel with the progression of mucosal atrophy and intestinal metaplasia. Results of immunohistochemical staining showed high incidence of secretory components in and around cancer foci, suggesting that immunological mechanisms for H. pylori infection play a role in the development of gastric cancer regardless of its histological type.

Adenocarcinoma↗
PubMed1982

Immunoglobulins in rabbit hepatic bile: selective secretion of IgA and IgM and active plasma-to-bile transfer of polymeric IgA.

Proteins in hepatic bile from cannulated rabbits were analysed by gel filtration, electrophoresis, density gradient ultracentrifugation, and immunochemical methods. Bile-to-serum concentration ratios (no. = 8) demonstrated that IgA and free secretory component (SC) were major constituents of rabbit bile. Relative concentration ratios, obtained by dividing the bile to serum level ratio for each protein by the corresponding ratio for albumin, were 310, 1.6, 1.0, 0.82, and 0.54 for IgA, IgM, albumin, transferrin, and IgG respectively, suggesting that both IgA and IgM are selectively secreted into bile. Ligation of the bile duct (no. = 5) led to a selective increase of the serum levels of IgA and SC, the latter as secretory IgA. After intravenous injection (no. = 4) of human polymeric IgA, 37-69% of the injected dose was recovered in bile after 3 h, in contrast to 4-5% for human monomeric IgA. The active transfer of both rabbit and human polymeric IgA into rabbit bile occurs via the same hepatic SC-mediated transport process as that described for the rat.

Animals↗
PubMed1987

Immunoregulatory properties of the proteins present in human milk.

The immunoregulatory properties of several proteins, isolated from human milk, were investigated. Secretory component and galactothermin exhibited immunoregulatory activities in the in vivo and in vitro assays, generating helper cells, changing the ARFC levels and the resistance of thymocytes to hydrocortisone (HC). In addition, the immunoregulatory action of the P protein and its four fractions was studied. The bulk of the activity was found in the fraction II and III. The results suggest that the postneonatal development of the mammalian immune system is under the surveillance of various immunoregulatory proteins contained in maternal secretory fluids.

Animals↗
PubMed1985

Induction of class II MHC antigens in cultured epithelial cells from rat gut.

A long-lived culture line of epithelial cells producing low levels of secretory component was derived from rat gut. Treatment of the cells with culture supernatants from rat spleen cells that had been stimulated with concanavalin A induced expression of class II antigens of the major histocompatibility complex and inhibited DNA synthesis.

Animals↗
PubMed1989

[Characteristics of local immunity in newborn infants].

The secretory immune system was found to be different in neonates and their mothers. The differences manifested in the low content of IgA and high content of the free secretory component in the child's saliva and tears as well as in neonatal milk. In order to study the local immunity of neonates, use was made of neonatal milk as a research object. The system of the complement C3-component synthesis on the mucous membranes appeared mature even in the neonatal period. Based on a comparative analysis of the subpopulations of the immunocompetent cells of blood and milk of neonates and their mothers the conclusion is made about the activation in the neonatal period of the immune system of the mucous membranes associated with the low functional activity of the systemic immunity. The comparative analysis of the immunosuppressive properties of the breast and neonatal milk has demonstrated that the low suppressor activity of secretory factors of the neonates' mucous membranes may be one of the causes of the local immunity activation.

Adult↗
PubMedDate not supplied

Laryngeal secretions. An immunochemical and immunohistological study.

This study was designed to investigate properties of laryngeal secretion and secretory activity of IgA in the larynx. Laryngeal secretions were collected by adsorption method on filter paper during laryngomicrosurgery from 20 patients having an inflammatory lesion in the larynx. Contents of IgG, IgA, IgE, secretory component (SC), and lactoferrin in the laryngeal secretions were determined and compared with results of those in nasal secretions, tracheobronchial washings, and serum samples obtained from the same subjects. The laryngeal mucosae of 8 laryngectomized materials for cancer lesion were subjected to immunofluorescence studies including the cytoplasmic SC affinity test. Results of this study indicate that laryngeal secretions are characterized by exocrine secretion, resembling nasal and tracheobronchial secretions in the electrophoretic pattern and immunoglobulins content. The immunofluorescence studies and SC affinity test found that the larynx possesses secretory activity of IgA, particularly in the ventricle and subglottis.

Adult↗
PubMed1986

Amino acid sequence of human plasma alpha 1B-glycoprotein: homology to the immunoglobulin supergene family.

The complete amino acid sequence has been determined for alpha 1B-glycoprotein (alpha 1B), a protein of unknown function present in human plasma. This protein (Mr approximately equal to 63,000) consists of a single polypeptide chain N-linked to four glucosamine oligosaccharides. The polypeptide has five intrachain disulfide bonds and contains 474 amino acid residues. Analysis of the amino acid sequence by several computer programs shows that alpha 1B exhibits internal duplication and consists of five repeating structural domains, each containing about 95 amino acids and one disulfide bond. alpha 1B has a unique amino acid sequence. However, several domains of alpha 1B, especially the third, show statistically significant homology to variable regions of certain immunoglobulin light and heavy chains. alpha 1B also exhibits sequence similarity to other members of the immunoglobulin supergene family such as the receptor for transepithelial transport of IgA and IgM and the secretory component of human IgA. Because of its internal duplication and its sequence homology to immunoglobulin-like proteins, alpha 1B appears to have evolved from an ancestral gene similar to that of the immunoglobulin supergene family.

Amino Acid Sequence↗
PubMed1999

Expression of a local immune defense system in the female genital tract. An immunohistochemical study.

UNLABELLED: The aim of this study was to investigate the presence of a local immunological defense mechanism of the secretory IgA class in the female genital tract. MATERIAL AND METHODS: We studied by a streptavidin-biotin method the secretory component (SC) and IgA distribution in paraffin-embedded sections of 90 formalin-fixed specimens. We studied 10 normal and 5 neoplastic cervical specimens, 20 normal, 10 hyperplastic endometrial specimens and 10 endometrial adenocarcinomas, 5 normal ovarian tubes and 30 ovarian epithelial neoplasms, serous and mucinous. A polyclonal SC and (Dako) and a mab IgA (Dako) was used and the reaction was scored from 1-3. RESULTS: Normal cervical mucosa and atrophic endometria were negative, while the basal portion of the endometrium, focally the proliferative glands, most of the secretory glands and most of the hyperplastic glands were positive for SC. IgA showed a similar distribution and a perivascular stromal reaction. Adenocarcinomas were positive for SC, but the intensity of the reaction was dependent on the differentiation of the tumors. Mucous and most serous neoplasms were negative for SC. IgA showed a similar reaction. CONCLUSION: There is evidence that the female genital tract has a local defensive immune system that may be hormone dependent. SC is a valuable marker of glandular differentiation.

Adenocarcinoma↗
PubMed1986

Morphogenesis of human colon cancer cells with fetal rat mesenchymes in organ culture.

The morphogenesis and cytodifferentiation of human colon cancer cells (LS174T and HT29) were examined by combining cancer cells with fetal rat digestive-tract mesenchyme in organ culture. LS174T cells migrated into the mesenchyme to form glandular structures composed of single columnar cells with their nuclei oriented basally, while HT29 cells formed cell masses with little lumen formation. Immunohistochemical studies with antibodies against carcinoembryonic antigen and secretory components showed that the composition of cell surface glycoproteins was not necessarily reversed to the normal type, even when neoplastic cells exhibited normal glandular structures.

Animals↗
PubMed1979

Immunohistochemical studies on the epithelial and lymphoid components of Warthin's tumour.

The lymphoid and epithelial elements of three Warthin's tumours (adenolymphomas) were studied by immunohistochemical technique. All classes of immunoglobulin (Ig)-producing cells were found, except IgE immunocytes. The numbers of cells/mm2 section area (median and range) were: 20.4 (15.2--27.2), 4.8 (2.8--12.4). 4.8 (0.4--9.6) and O (0--1.2) for IgG-, IgA-, IgM- and IgD-producing cells respectively. This gives percentage class ratios (68:16:16:0) which are quite different from those found in normal parotid tissue (3.6:91:3.1:2.6). Thus, the immunocytes found in Warthin's tumour are clearly polyclonal and show a class distribution comparable to that of lymphoid organs such as the tonsils. Also as in such organs, there were lymphoid follicles with mantle zone of B lymphocytes bearing membrane-bound IgM and IgD, and germinal centres showing reticular IgM staining. Apical staining for IgA and secretory component (SC) was shown in the luminal cells of the tumour epithelium, giving a fluorescence pattern similar to that of normal striated ducts. Selective transport of IgA apparently taken place into the cystic spaces of the tumour. Carcino-embryonic antigen (CEA), normally absent from striated ducts, was not generally present in the tumour epithelium, but was found in small groups of cells, especially in papilliferous parts of the epithelium. Warthin's tumour therefore seems to be composed of a fairly inactive normal lymphoreticular tissue and a neoplastic duct epithelium, most of which is highly differentiated with retention of immunoglobulin transport.

Adenolymphoma↗
PubMed1981

Medullary carcinoma of breast: an immunohistochemical study of its lymphoid stroma.

Immunoperoxidase staining for IgA, IgG, IgM, and secretory component (SC) was performed on ten cases each of medullary carcinoma and infiltrating duct carcinoma of breast. Plasma cell-rich stroma of medullary carcinoma was found to contain predominantly IgA plasma cells. Tumor cells also contained IgA and SC. In contrast, the few plasma cells of infiltrating duct carcinoma were found to be predominantly IgG type, and the tumor cells contained none or very small amounts of IgA and SC. Because the presence of IgA plasma cells and IgA and SC in lining epithelial cells are characteristic features of organs of the secretory Ig system, these findings in medullary carcinoma may suggest a good degree of functional differentiation of these tumor cells and correlate well with the well-known favorable prognosis associated with this tumor.

Breast Neoplasms↗