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At least 19 recordsLinked to original sources
PubMed1991

Characterization of a critical binding site for human polymeric Ig on secretory component.

Secretory component (SC) is an integral membrane glycoprotein of secretory epithelial cells which is responsible for the specific transport of polymeric Ig (PIg) to external mucosal surfaces. The ectoplasmic segment which binds polymeric Ig is comprised of five Ig-type domains. Chemically and enzymatically modified forms of the ectoplasmic portion of SC (FSC) were produced and tested for their ability to bind to PIgA and PIgM. Deglycosylated FSC bound specifically to PIg, indicating that N-linked carbohydrate moieties on FSC are not required for binding. Denatured, reduced, and alkylated FSC did not bind to PIgA, and bound to PIgM with significantly reduced affinity, suggesting that native conformation of the polypeptide backbone of SC was important to binding. Tryptic fragments of FSC which bound to PIg were isolated and identified to be derived from domain I of SC. Synthetic peptides comprising overlapping portions of domain I bound to PIg to varying degrees. The strongest affinity was demonstrated by a peptide comprised of residues 15 to 37 of SC. A comparison of the amino acid sequences of human, rabbit, and rat SC indicated that this region contained a high degree of residue identity (78%) and may represent a consensus sequence for binding of FSC to PIg. Importantly, the peptide comprised of residues 15 to 37 was also recognized by a monoclonal antibody, 6G11, which inhibited the binding of FSC to PIgA. These results demonstrate that the binding of human SC to PIg is critically dependent on a highly conserved peptide region within the first domain of SC centering at residues 15-37.

Amino Acid Sequence↗
PubMed1991

The usefulness of routine screening for salivary secretory component.

Secretory IgA is a dimeric immunoglobulin found in association with the J chain and secretory component (SC). It is secreted into saliva and other mucosal fluids and is involved in mucosal immunity. The absence of either SC or secretory IgA may be associated with recurrent sinopulmonary infections, diarrhea, and failure to thrive. We present a retrospective study of 1262 samples from 877 patients who were screened for salivary IgA, SC, and serum immunoglobulin levels. Forty-six patients (5.2%) of those tested were found to have absent salivary SC. Although only 19 of these patients (41.3%) could be retested, all were found to have SC on repeated testing. Of the patients whose initial samples of saliva exhibited no SC, 15% (6/46) had low or absent serum IGA (less than 10 mg/dl) in contrast to 8.6% (66/769) of patients whose saliva contained detectable SC, but this was not statistically significant (chi 2 = 1.93; p greater than 0.1). There was also no correlation between serum immunoglobulin levels and the absence of SC. Because of the rarity of salivary SC deficiency, routine screening is not valuable.

Aging↗
PubMed1979

Human secretory component. II. Easy detection of abnormal amounts of combined secretory component in human sera.

A simple method, allowing easy detection of abnormally increased sIgA levels is described. It consists in quantitation of combined SC by gel double diffusion, using appropriate anti-SC immune sera. The technical conditions, locating the threshold of sensitivity of precipitation at about 25 microgram/ml, a value higher than that found in normal sera, were established. Comparison with other classical methods (SRID, ELISA and IHA) emphasizes the validity and simplicity of the technique which has shown convenient whenever a large number of sera have to be tested.

Antibody Specificity↗
PubMed1975

Increased risistance of immunoglobulin A dimers to proteolytic degradation after binding of secretory component.

The contribution of secretory component to the stability of secretory IgA against proteolysis has been studied by a new approach, i.e., by comparing the proteolytic degradation of the complexes formed in vitro between these proteins and secretory component. The results show that attachment of secretory components to the dimeric backbone of the secretory IgA molecule is accompanied by a significantly increased resistance of this backbone against digestion by both trypsin and pepsin. This protective effect may be a physiologic function of secretory component or may be due merely to unspecific blocking by secretory component of one or more sensitive peptide bonds in the IgA backbone.

Absorption↗
PubMed1979

Structure of the carbohydrate chain of free secretory component from human milk.

Secretory component from human milk was found to contain 23.4% carbohydrate, which includes galactose, mannose, fucose, glucosamine, and sialic acid. Secretory component could be degraded by pronase or base-borohydride to yield the same, single type of carbohydrate chain. In the glycopeptide produced by pronase digestion, aspartic acid was the only amino acid present in molar quantities after amino acid analysis, which suggests that the carbohydrate moiety is linked to the polypeptide chain at asparagine residues. The positions of links between the various sugar units were studied by methylation analyses of: secretory component, periodate-oxidized and reduced secretory component, the fragment produced by base-borohydride treatment, and the pronase glycopeptide after treatment with specific glycosidases. Sugars released from the glycopeptide by various glycosidases were also quantitated. From the results of these studies a branched chain structure was assigned to the carbohydrate chain of secretory component.

Amino Acids↗
PubMed1976

Synthesis of secretory component by colonic neoplasms.

The secretory component (SC) polypeptide chain of secretory immunoglobulin A can be considered as a differentiation marker in that it is normally synthesized in the non-mucus-containing columnar epithelial cells, but not goblet cells, of the large intestine. With this in mind, we have studied the expression of SC in 36 colonic adenocarcinomas and 15 polyps (adenomatous and villous) by the fluorescent antibody technique. As in the normal mucosa, the synthesis of SC in tumors found in non-mucus-containing columnar cells and was absent from goblet cells. However, in several well-differentiated carcinomas it appeared that columnar cells contained both SC and mucin; these cells could be analogous to the normal mucosal precursor of both cell types. SC was synthesized throughout all adenomatous polyps and villous adenomas with the exception of some atypical nonmucinous areas of adenomatous polyps. Secretory component synthesis by carcinomas was associated with mucus production, although goblet cells did not contain SC. The presence of SC also correlated with the degree of differentiation. Secretory component was absent from half of the carcinomas as well as from atypical nonmucinous areas of polyps, and this could represent one of the earliest changes associated with the development of malignancy.

Adenocarcinoma↗
PubMed1975

Secretory component in human mammary carcinoma.

Since secretory component is thought to be a normal glandular epithelial cell product, surgical specimens from patients with mammary carcinoma, an epithelial cancer, were studied with antisera to human free secretory component by indirect immunofluorescence microscopy. Normal breast tissue (10 cases) showed fluorescent epithelial cells confined to normal ducts. This was in marked contrast to ubvasive mammary carcinoma (20 cases), which showed intense staining of tumor cells and stromal cells in addition to the normal ductular epithelium. Metastases in axillary lymph nodes (2 cases) showed intense fluorescence for secretory component, whereas axillary nodes without metastases from 2 patients with breast cancer showed no fluorescence. In both normal and tumor tissue, antiimmunoglobulin A stained only ducts and subepithelial plasma cells, thus establishing that the secretory component in tumor cells was not part of an intact secretory immunoglobulin A molecule. This finding was not restricted to mammary carcinoma, since preliminary studies of colon, lung, and bladder carcinoma also demonstrated tumor cells with cytoplasmic fluorescence for secretory component. In contrast, the tumor cells in 2 cases of sarcoma, a nonepithelial cancer, did not exhibit fluorescence for secretory component.

Animals↗
PubMed1975

Distribution of covalently bound and non-covalently bound secretory component on sbuclasses of rabbit secretory IgA.

The distribution of non-covalently bound secretory component (SC) on the two subclasses, IgA-f and IgA-g of rabbit secretory IgA (sIgA) was determined; the two subclasses were separated from each other by the use of antibody-immunosorbent columns and were subjected to SDS polyacrylamide gel electrophoresis. No SC appeared to be dissociated from the IgA-f molecules from each of 11 different rabbits; the IgA-g molecules, however, did have SC which was dissociated by SDS. Thus, all of the noncovalently bound SC on rabbit sIgA resides on the IgA-g subclass molecules.

Animals↗
PubMed1991

The presence and measurement of secretory component in human bile and blood.

Five monoclonal antibodies which recognized three separate epitopes on the free secretory component molecule were produced using free secretory component obtained from human colostrum. Two-site immunoradiometric assays were developed to measure free secretory component and secretory IgA. Monoclonal antibody M9 was used on coated plates as the capture antibody. Monoclonal antibody M7 was used as the labelled signal antibody for the assay of free secretory component and a commercially available monoclonal anti-IgA antibody was used as the labelled signal antibody for the assay of secretory IgA. Free secretory component was found in human serum and bile. In serum, its concentration was raised in patients with high serum alkaline phosphatase due to liver disorders but not in patients with high serum alkaline phosphatase due to non-liver disorders. In bile from bile duct drains collected during the first week after liver transplantation, free secretory component was found in concentrations of up to 33 mg/l, in vast excess of that found in bile from gallstone patients (up to 0.3 mg/l). Bile from gallstone patients but not from liver transplant patients produced proteolytic degradation of free secretory component when incubated in vitro. The finding of large amounts of free secretory component, the free cleaved fragment of the polymeric IgA receptor in human bile, further supports the existence of the blood to bile transhepatocytic pathway in humans.

Alkaline Phosphatase↗
PubMed1976

Binding of secretory component to human immunoglobulin M.

The binding of human free secretory component to immoglobulin M (IgM) has been studied in vitro as a model for the formation of complexes between the two proteins in vivo. Three IgM myelomas and normal serum IgM were found to bind secretory component in amounts from 0.8 to 2.0 mol per mol of IgM. This variation in binding was not related to a corresponding variation of the J-chain content of the immunoglobulins, but more likely it was due to varying amounts of unspecifically bound serum proteins blocking the attachment of secretory component. In contrast to complexes with immunoglobulin A (IgA), the binding of secretory component to IgM appeared to be solely of a noncovalent nature, as all secretory component was released from complexes with IgM during gel chromatography in 6 M guanidine hydrochloride. Studies with tryptic fragments of one of the IgM myelomas indicated that the binding site for secretory component is located on the (Fc)5mu part of the IgM pentamer. Finally, only minimal conformational changes were found to accompany complex formation between secretory component and IgM, analogous to what has earlier been reported for the attachment of the secretory component to IgA.

Binding Sites↗
PubMed1991

Serum and bile secretory immunoglobulins and secretory component during the early postoperative course after liver transplantation.

Secretory component was assayed in serum and bile from 34 patients within 40 days after a first or a second (three cases) liver transplantation. Levels of serum secretory IgA and IgM and of a serum component referred to as immunoreactive free secretory component, identified by its reactivity with monoclonal and polyclonal antibodies specific to secretory component, were significantly elevated in all posttransplant patients compared with 45 healthy subjects and 10 kidney transplant patients (p less than 0.0001). The highest serum levels of bound secretory component and of immunoreactive free secretory component were observed in patients with acute rejection. The elevation of immunoreactive free secretory component was significantly higher in patients with rejection as compared with patients with a graft ischemia (p = 0.002) or an uncomplicated postoperative evolution (p = 0.01). The highest levels of immunoreactive free secretory component and secretory IgM were observed in a transplant patient with selective IgA deficiency. No significant difference was seen between the levels of serum immunoreactive free secretory component observed in patients with rejection and those of patients with cytomegalovirus hepatitis or sepsis. Immunoreactive free secretory component, secretory IgA and secretory IgM levels measured in the serum of three patients with primary nonfunction were lower than those observed in the other groups. Immunoreactive free secretory component bile/serum ratios calculated from 16 patients were significantly higher in patients with acute rejection than in infected patients. This study provides new insight into the mechanisms of increase of serum immunoreactive free secretory component, secretory IgA and secretory IgM in various types of liver dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Probing the topography of free and polymeric Ig-bound human secretory component with monoclonal antibodies.

Secretory component (SC), an integral membrane protein expressed on basolateral surfaces of secretory epithelial cells, mediates the transport of polymeric Ig (PIg) into external secretions. The ectoplasmic segment of SC is released into secretions either in a free form (FSC) or bound to PIg as secretory IgA or IgM. The topography of human SC in its free and PIgA-bound form was studied by using mAb directed against each form of SC. Competition experiments identified a minimum of nine SC epitopes, one of which was dependent on an N-glycosidic moiety. Three of the polypeptide-derived epitopes were displayed on denatured, reduced, and alkylated SC, whereas the others were fully or partially dependent on the native conformation of SC. Epitopes recognized by the latter class of antibodies were mapped to discrete domains of SC, based on amino acid sequence and antibody-binding analysis of limited proteolytic fragments. One of the mAb (6G11), which was directed against an epitope on domain I of SC, inhibited the binding of FSC to PIgA. Overall, our results provide evidence that a region within domain I, as well as protease-sensitive interdomain regions of FSC, become masked or altered when SC binds to PIgA. Furthermore, the binding of SC to PIgA results in conformational changes, or formation of combinatorial epitopes, involving regions within domains II and III of SC but not domain V.

Alkylation↗
PubMed1975

Structural composition of canine secretory component and immunoglobulin A.

Dog serum and colostral immunoglobulin A (IgA) and free secretory component from colostrum were isolated using affinity chromatography. Both serum and colostral IgA showed similar susceptibility to reduction with dithiothreitol, but only colostral IgA released the additional subunit, bound secretory component. This released secretory component was identical with free secretory component with respect to electrophoretic migration, isoelectric focusing point, and molecular weight, but lacked some antigenic determinants. The amino acid composition and the N-terminal sequence of canine free secretory component was similar to that reported for the cow.

Amino Acids↗
PubMed1992

Circulating secretory component in relation to early diagnosis and treatment of liver metastasis from colorectal carcinomas.

AIMS: To evaluate serum secretory component in relation to early detection and clinical management of liver metastasis in patients with colorectal cancer. METHODS: Secretory component and carcinoembryonic antigen (CEA) were analysed in serial serum samples from 23 patients who had liver metastases as the only apparent recurrence, and in sera from 54 matched controls. Results of surgical treatment of recurrences were classified peroperatively as radical when no residual tumour was apparent and resection margins were free of disease. RESULTS: In total, 18 (78%) patients had increased secretory component during the whole follow up period (median 16 months); 12 (52%) had raised secretory component concentrations before clinical recurrence (median lead time 5.2 months). There was no difference before recurrence between circulating secretory component and CEA in sensitivity and lead times. Seventeen patients underwent surgery for hepatic metastasis; seven had radical hepatic resection of which only two (29%) showed increased secretory component concentrations before clinical recurrence; both had concurrent raised CEA values. By contrast, secretory component was raised in 83% of those cases considered inoperable. CONCLUSIONS: Although serum secretory component clearly increases in most patients with liver metastases, its clinical value seems questionable because secretory component apparently indicates mainly inoperable hepatic metastases.

Adult↗
PubMed1977

Disulfide bonding of secretory component to a single monomer subunit in human secretory IgA.

The arrangement of disulfide bonds joining secretory component (SC) to the alpha chains in secretory IgA was studied by determining the molecular size of the principal fragments resulting from CNBr digestion of secretory dimeric Fc fragments from IgA (Fc)2alpha fragments). In vitro complexes formed by incubating 125I-free SC and myeloma 131I-(Fc)2alpha fragments were isolated by gel filtration and subsequently digested with cyanogen bromide. The CNBr digests of SC-(Fc)2alpha fragments were analyzed by gel filtration in 5 M guanidine. Two principal fragments were obtained, one containing a monomeric Fc fragment from IgA (Fcalpha) associated with SC (m.w. congruent to 110,000) and a second containing the second Fcalpha monomer (m.w. congruent to 50,000) from the dimeric SC-(Fc)2alpha. Similar results were obtained when secretory (Fc)2alpha fragments isolated from native secretory IgA dimer were subjected to CNBr digestion. The data indicate that SC is disulfide bonded to a single monomer subunit in secretory IgA dimer.

Chemical Phenomena↗