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PubMed1981

Relation between HLA-DR-like antigens and secretory component (SC) in jejunal epithelium of patients with coeliac disease or dermatitis herpetiformis.

HLA-DR-like antigens and secretory component (SC) were localized immunohistochemically in adjacent tissue sections of ethanol-fixed paraffin-embedded jejunal mucosa from control subjects and patients with coeliac disease (CD) or dermatitis herpetiformis (DH). HLA-DR-like antigens were found in a patchy distribution apically in the columnar epithelial cells facing the gut lumen and in the upper part of the crypt epithelium. The staining pattern was similar in controls and patients with CD or DH. SC was normally most abundant in the crypt epithelium but the concentration of SC in the surface epithelium increased with increasing villous atrophy both in CD and DH patients. Despite this sign of immaturity, the surface cells retained their capacity to express HLA-DR-like antigens in the pathological mucosa.

Adolescent↗
PubMed1986

Immunohistochemical distribution of immunoglobulin and secretory component in the ileum of normal and paratuberculosis-infected cattle.

The immunohistochemical distribution of IgA, IgG, IgM and secretory component in the ileum of 10 normal and 21 paratuberculosis-infected cattle was investigated. Semi-quantitative analysis of the number of each class of Ig-containing cells in the lamina propria mucosa of infected ileums showed that IgG and IgM-containing cells and total Ig-containing cells were significantly more numerous than those in the normal ileums. There was no significant difference in the numbers of IgA-containing cells between the two groups of cattle. The distribution of IgA, IgM and SC was basically similar in the two groups. However, IgG-containing cells characteristically accumulated around the granulomas. It was considered that excessive local production of Ig in the intestinal mucosa, along with subsequent formation of immune complex or release of histamine from mast cells, could account for the occurrence of diarrhoea and participate in the pathogenesis of bovine paratuberculosis. A comparison of the local immunological state in paratuberculosis and Crohn's disease was made.

Animals↗
PubMed2000

Immunohistochemical study of ceruloplasmin, lactoferrin and secretory component expression in neoplastic and non-neoplastic thyroid gland diseases.

The expression of lactoferrin (LF), ceruloplasmin (CP) and secretory component (SC) in various thyroid diseases was investigated using an immunohistochemical method. LF is an iron-binding protein overexpressed in certain human adenocarcinomas. CP is implicated in carcinogenesis and SC is part of the local immune defense system. Sections of 15 follicular adenomas, 5 follicular carcinomas (FC), 16 papillary carcinomas (PC), 15 goitres and 2 cases of lymphocytic thyroiditis were re-examined and investigated immunohistologically by a streptavidin-biotin method. A positive immunostain reaction for CP and LF was observed in all cases of PC and FC. A positive immunostain reaction for SC was observed in 13/16 cases of PC and 4/5 cases of FC. A negative immunostain reaction for CP, LF and SC was observed in medullary cancers, in follicular adenomas and in the cases with goitre. We conclude that the immunostain expression of LF, CP and SC is a valuable diagnostic aid in the differential diagnosis between benign and malignant thyroid tumors. The expression of SC indicates the presence of a local immunodefensive system.

Adenocarcinoma, Follicular↗
PubMed1981

Distribution of immunoglobulin-containing cells and localization of secretory component in gastric mucosa bearing carcinoma.

Surgical materials of gastric carcinoma were studied immunohistochemically in terms of the distribution of immunoglobulin-containing cells and the localization of secretory component (SC). There was no convincing evidence suggesting that the secretory immune system surrounding carcinoma was responding to the carcinoma. But in some cases, increase of IgG-containing cells was observed in the stroma of carcinoma suggesting the presence of some kind of tumor immunity. In the non-carcinomatous mucosa, SC was observed strongly in cells of intestinal metaplasia except for the goblet cells, but weakly in the normal foveolar epithelium. The presence of SC in carcinoma cells was observed in 45 percent of the total cases of gastric carcinoma [36/80] and was especially prominent in signet-ring cell carcinoma [78%]. IgA was observed in about 50 percent of these SC-positive carcinoma cases. SC was also frequently positive in group III atypical epithelium.

Carcinoma↗
PubMed1991

Immunohistochemical study of colorectal adenocarcinomas and adenomas with antibodies against carcinoembryonic antigen (CEA), CA19-9, keratin, alpha-tubulin and secretory component (SC).

The immunohistochemical localization of five antibodies against carcinoembryonic antigen (CEA), CA19-9, keratin, alpha-tubulin and secretory component (SC) was investigated in 14 lesions of adenocarcinoma (AC), 22 of adenoma with high-grade atypia (AH), 50 of adenoma with low-grade atypia (AL), and 15 of non-neoplastic mucosa (NNM) of the large intestine. The positive patterns for each staining were divided into three categories (patterns 1, 2, and 3). All neoplastic lesions (AC, AH and AL) were positive for CEA, while 85.7% of AC, 36.4% of AH and 6.0% of AL showed strongly positive staining (pattern 3). 78.6% of AC and 54.5% of AH were positive for CA19-9 in comparison to 20.0% of AL. For keratin, more than 95% of the neoplastic lesions were positive, while 78.6% of AC, 27.3% of AH and 22.0% of AL showed strongly positive staining (pattern 3). For alpha-tubulin, more than 85% of neoplastic lesions were positive, while 50.0% of AC, 36.3% of AH and 26.0% of AL showed strongly positive staining (pattern 3). For SC, in contrast, 42.9% of AC, 27.3% of AH and 8.0% of AL were negative, but 93.3% of NNM were positive. It was concluded that the positive staining rate, especially the rate of pattern 3 for each antibody correlated with the degree of atypia of the colorectal neoplastic lesions (AC, AH and AL).

Adenocarcinoma↗
PubMed1983

Variations in free secretory component levels in mucosal secretions of the rat.

The present studies were conducted to compare the levels of free secretory component (SC) in a number of rat mucosal secretions and to determine whether SC content varies significantly during the four stages of the estrous cycle. Levels of SC, as measured by radioimmunoassay, were markedly different in various external secretions. Bile contained the highest amount, irrespective of whether SC was normalized to volume or protein. Concentrations of SC in saliva or uterine fluid from intact rats were approximately 20- to 30-fold less than measured in bile. When SC levels were normalized to protein, the SC to protein ratios in uterine, vaginal, and respiratory secretions were six to 18 times greater than values calculated in salivary and small intestinal fluids. Analysis of SC levels in mucosal secretions during the estrous cycle indicated significant variations occur in uterine and vaginal samples, but not in saliva or small intestinal secretions. In the uterine lumen, SC levels were highest at proestrus, partially elevated at estrus, and lowest at both days of diestrus. In contrast, vaginal SC levels were maximal at estrus and reduced at all other stages of the cycle. Immunoglobulin A content was also measured in uterine and vaginal secretions during the estrous cycle. Significant changes in IgA levels were found and these coincided with the changing pattern of SC. These results suggest hormones may modulate SC levels in reproductive tissues. In addition, our findings indicate variations in SC during the estrous cycle may direct the movement of IgA from tissue to lumen.

Animals↗
PubMed1991

Influence of culture conditions on the androgen control of secretory component production by acinar cells from the rat lacrimal gland.

Research has shown that androgens regulate the production of secretory component (SC), the IgA antibody receptor, by lacrimal gland acinar cells in vivo. This study was designed to establish an optimal culture system to permit analysis of this endocrine-acinar cell interrelationship in vitro. Acinar cells were isolated from male rat lacrimal glands and cultured on Matrigel (Collaborative Research, Bedford, MA) in serum-free Dulbecco's modified Eagle's medium (DMEM)/Ham's F12 media that contained a variety of supplements. Under these conditions, acinar cells responded to dihydrotestosterone (DHT) exposure with a significant increase in SC output. Replacement of the DMEM/Ham's F12 media base with either Modified Eagle's Medium (MEM) or low-calcium MEM inhibited this hormone response and dramatically reduced cell recovery after 4 days of culture. Similarly, decreased concentrations or deletions of selected media supplements, including insulin, which binds to acinar cells, and dexamethasone, led to a significant diminution in the extent of androgen action, as well as to a decline in cell maintenance. In contrast, removal of high-density lipoprotein from culture media or the addition of fetal bovine serum (FBS) or cholera toxin significantly enhanced basal and DHT-associated SC production by acinar cells. With regard to extracellular matrices, Matrigel proved to be superior to collagen type I, laminin, fibronectin, or the Primaria (Falcon, Oxnard, CA) plastic surface in providing support for acinar cell association or hormone-related function. In summary, our results show that the media formulation, supplement profile, and extracellular matrix composition are important for maximal expression of androgen-induced effects by lacrimal gland acinar cells in vitro.

Androgens↗
PubMed1993

Nonspecific increased serum levels of secretory component in lung tumors: relationship to the gene expression of the transmembrane receptor form.

Polymeric immunoglobulin receptor (pIg-R) is synthesized by epithelial cells lining the bronchial mucosa. It is released in secretions as free secretory component (SC) or bound to Ig as secretory Ig (S-IgA and S-IgM). To evaluate the usefulness of SC and pIg-R expression as tumour markers, we measured SC and secretory Ig, using enzyme-linked immunosorbent assay, in the serum of 45 patients with lung carcinomas, in the serum of 10 patients with non-neoplastic diseases, and in the serum of 45 control subjects. We also studied the immunohistochemical expression of pIg-R and its mRNA in tumors from 20 out of the 45 patients. Serum levels of SC and S-IgA were similarly and significantly elevated in patients with lung cancer (squamous cell carcinoma [25 cases], small cell carcinoma [7 cases], adenocarcinoma [13 cases]) and with non-neoplastic diseases, as compared with control subject levels (P < 0.001). The highest SC levels were found in patients with adenocarcinoma although the mean SC level was not different from other pathologic conditions. pIg-R was usually not detected in the cells of small cell carcinoma or of squamous cell carcinoma, whereas it was found in the cells of five adenocarcinomas and in the two in situ carcinomas under study. The specific mRNA analysis usually agreed with the immunolocalization of pIg-R. A single band at 3.8 kb was detected in the positive tumor tissues and in normal lung tissues. However, the signal was weak in one case of squamous carcinoma and stronger in two out of three adenocarcinomas, than in normal tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

Effect of a disulfide-interchange enzyme on the assembly of human secretory immunoglobulin A from immunoglobulin A and free secretory component.

A disulfide-interchange enzyme from rat liver microsomes was found to promote binding in vitro of human free secretory component (SC) to dimeric serum-type IgA containing J chain, as assessed by immune precipitation and gel filtration. This effect was greater withe native than with partially reduced SC. Most of the bound SC was covalently linked, as determined by electrophoresis in polyacrylamide gels in detergent. The enzyme did not promote binding of native or partially reduce SC to IgG, IgA monomer, IgA dimer without J chain, or IgM. In the case of IgM, the enzyme did, however, promote covalent bonding of previously non-covalently linked SC. The results overall suggest that a disulfide-interchange enzyme could play a role in vivo in the cell-associated assembly of secretory IgA by promoting the covalent attachment of SC to a dimer of serum-type IgA and that the J chain in the IgA dimer contributes to the enzyme effect.

Animals↗
PubMed1976

Synthesis of secretory component by human colon cancer cells.

Colon carcinoma, established in long-term tissue culture, has been shown to synthesize secretory component (SC). These molecules can be demonstrated both on the cell surface and in the cytoplasm by immunofluorescence. Regeneration of SC was demonstrable after trypsinization of the cells. In culture, two lines of carcinoma epithelium were shown to incorporate (14C) leucine into newly synthesized SC. These cell lines should provide useful preparations for studying the details of immunoglobulin-SC interactions.

Cell Line↗
PubMed1990

[Intrahepatic IgA and secretory component distribution and the mechanism of hyperSigAnemia].

Using immunohistochemical techniques, the authors observed the distribution and localization of IgA and secretory component (SC) in normal and hepatolithiasis livers, and measured the serum level of IgA by means of sandwich enzyme immunoassay (EIA). It was found that in normal livers positive reaction for SC and IgA could only found in epithelial cells of biliary canals. While in hepatolithiasis livers strong positive reaction for IgA and SC were also found in dilated bile canaliculi and the sinusoids. These results suggest that the epithelia of biliary canals take part in the formation and transferring of IgA and the backflow of IgA into blood stream under high pressure may cause hyper SIg A nemia.

Bile Ducts, Intrahepatic↗
PubMed1979

Immunoelectron-microscopic localization of immunoglobulin A and secretory component in jejunal mucosa from children with coeliac disease.

Using peroxidase-labelled antibodies, the ultrastructural localization of IgA and secretory component (SC) was investigated in duodeno-jejunal biopsies from six children with coeliac disease and compared with that observed in non-coelic mucosa. In normal intestinal mucosa this study confirmed the presence of IgA in the rough endoplasmic reticulum and the perinuclear space of numerous subepithelial plasma cells and one the lateral cell membranes of villous and especially crypt epithelial cells. SC was only detected in the epithelium and principally in crypt epithelium where it was identified in endoplasmic reticulum, Golgi saccules, perinuclear spaces and on lateral cell membranes. These findings support the suggestion that SC is synthesized mainly in crypt epithelium and acts as a receptor on epithelial cell membranes for dimeric IgA. In untreated coeliac patients, SC was observed at the same sites, but SC staining was reduced in damaged surface epithelial cells. The number of IgA immunocytes was increased and heavy deposits of IgA were found on basement membranes. In post-treatment biopsies, no abnormality was apparent. After re-exposure to gluten, depositions of IgA on basement membranes were the only early change. The unaltered distribution of SC and IgA in crypt epithelium strongly suggests that the epithelial transport mechanism of secretory IgA is normal in coeliac disease.

Basement Membrane↗
PubMed1983

Estimation of polymeric IgA in human serum: an assay based on binding of radiolabeled human secretory component with applications in the study of IgA nephropathy, IgA monoclonal gammopathy, and liver disease.

Binding of 125I-human secretory component (SC) to human polymeric immunoglobulin A (pIgA) was employed to measure quantitatively the pIgA present in human sera. Interference by IgM in some sera was prevented by removal of IgM with glutaraldehyde polymerized anti-IgM antibodies. 125I-SC complexed to pIgA was measured by precipitation with anti-IgA antibodies and the quantity of pIgA in human serum was estimated by comparing the quantity of 125I-SC bound by several dilutions of human serum to that bound by standard quantities of human monoclonal pIgA proteins. The assay was specific for pIgA because heat-aggregated monomeric IgA or hypogammaglobulinemic serum did not bind 125I-SC greater than a precipitate formed with human monoclonal IgG and anti-IgG. Moreover, analysis of a series of IgA myeloma sera indicated no correlation between the IgA content of the serum and the quantity of pIgA measured. The quantity of pIgA found in 30 normal human sera was 0.13 +/- 0.08 mg/ml (1S.D.), which consisted of 11.3 +/- 5.3% (1 SD) of the total IgA. Patients with IgA monoclonal gammopathy were most often found to have predominantly monomeric IgA. Patients with IgA nephropathy also showed an elevation of pIgA, but this appeared to be a consequence of an overt IgA elevation. IgA nephropathy patients with elevated serum IgA in fact showed a significant elevation of monomeric IgA. Selective elevation of pIgA was observed in patients with primary biliary cirrhosis and alcoholic liver disease. A comparison of this assay with other assays to measure pIgA is discussed.

Aged↗
PubMed1989

[Bile fractions and bile secretory component of the migrating myoelectric complex in dogs].

In 4 dogs the functional cholecystectomy was performed, then the common bile duct was cannulated and 9 bipolar electrodes were implanted into the stomach and small intestine. During the interdigestive period when the experiments were carried out both bile flow and electric activity of the gastrointestinal tract were monitored under the following conditions: 1) short or long bile depletion periods, 2) intraduodenal infusions of 50 mM sodium taurocholate, sodium taurodeoxycholate or sodium taurochenodeoxycholate, 3) intraduodenal bile infusions. Total bile acid content was determined in bile samples, then both bile acid-dependent (BAF) and bile acid-independent fractions (BAIF) of bile were calculated. The appearance of the bile secretory component was in 65% correlated with phase III of the MMC while the height of its amplitude usually exceeded 100% of the initial value. In all experimental groups the marked increase in BAIF was followed by a slight enhancement of BAF or its absence. Fluctuations of the biliary fractions were determined by a degree of depletion of the systemic bile acid pool. The changes described were more distinct during infusions of dihydroxy bile acids. The results suggest the importance of BAIF in the appearance of the bile secretory component of the MMC.

Action Potentials↗
PubMed1993

Increased levels of a lower molecular weight form of secretory component in cervical scrapes from women with cervical intraepithelial neoplasia.

The protein composition of 'negative' and 'positive' cervical scrapes has been compared using electrophoresis to determine whether differences were present that could be used to pre-select specimens with negative cytology. Only one minor difference in the 75-80 kDa region of the silver-stained patterns was detected in extracts from two well-matched groups. Further studies using 2D-electrophoresis and Western blotting identified the major components in this region as two forms of secretory component (SC) and transferrin. Subsequent blotting of 13 extracts from patients with negative smears and 17 extracts from patients with positive smears indicated very significant differences in the expression of the two forms of SC (P < 0.0002), the 'negatives' having more of the higher Mr form and the 'positives' having more of the lower Mr form. Measuring SC could prove useful for pre-screening cervical scrapes, but more investigations are required to establish the nature of the change and a quantitative method for its detection.

Journal Article↗
PubMed1984

Hormonal influence on the secretory immune system of the eye: androgen regulation of secretory component levels in rat tears.

The present study examined the influence of gender and steroid hormones on the level of free secretory component (SC) in tears of rats. The SC concentration in tears of male rats was approximately five-fold greater than that found in tears of females. This difference could not be accounted for by variations in tear volume or a suppression of tear SC content in female rats during certain stages of the estrous cycle. Rather, the elevated level of SC in tears of males appeared to be due to the effect of androgens. Castration of male, but not female, rats resulted in a time-dependent decrease in the SC content of tears. Administration of testosterone to orchiectomized rats reversed this decline and induced a time- and dose-dependent increase in the tear SC concentration. This response appeared specific for androgens, because treatment of orchiectomized rats with progesterone, estradiol, or cortisol had no effect on total tear SC. Consistent with this hypothesis was our finding that injection of castrated male rats with 5 alpha-dihydrotestosterone also raised the tear SC concentration. Of interest, the androgen-induced increase of the SC level in tears was not accompanied by similar changes in total tear protein. These results suggest that androgens may influence the production and/or secretion of SC by ocular tissues. Furthermore, our findings indicate that androgens play a role in the ocular secretory immune system of the rat.

Androgens↗
PubMed1990

Androgen regulation of secretory component synthesis by lacrimal gland acinar cells in vitro.

This study sought to determine whether androgens directly stimulate the production of secretory component (SC) by acinar cells from the rat lacrimal gland. Homogeneous populations of acrinar cells were isolated from lacrimal tissues by serial enzymatic digestion and Ficoll gradient centrifugation and then cultured on reconstituted basement membranes in supplemented, serum-free medium. Acinar cell exposure in vitro to dihydrotestosterone (DHT) resulted in a significant increase in cellular SC output. This hormone action was dose dependent and androgen specific. Testosterone, but not 17 beta-estradiol, progesterone, dexamethasone, or aldosterone, also induced a considerable elevation in acinar cell SC production. The effect of testosterone may not require intracellular enzymatic conversion to DHT. The impact of androgens on SC output was associated with enhanced cellular synthesis and secretion and did not involve variations in acinar cell viability or density. Moreover, the SC response to DHT occurred irrespective of whether lacrimal gland acinar cells were obtained from young adult male or female rats. In contrast, the androgen-related rise in SC production was significantly reduced in acinar cells isolated from tissue of orchiectomized and hypophysectomized rats. In summary, these findings demonstrate that androgens directly increase the synthesis of SC by lacrimal gland acinar cells in vitro. This effect, however, may be significantly altered by prior changes in the endocrine environment of acinar cells in vivo.

Aldosterone↗