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PubMed1975

Studies on human dental plaque. 2. Immunochemical characteristics.

From collected supragingival plaque, extracts were prepared for immunochemical analyses. Extracted sediments were examined by fluorescein-labeled antibodies for the presence of immunoglobulins. Precipitation with monospecific and polyvalent antisera revealed IgA, IgG, secretory component, C3, alpha2macroglobulin, lactoferrin, and albumin in the extracts. Gel filtration of pooled plaque extract yielded two fractions that contained the aforementioned proteins and a prominent, dialyzable third fraction that was immunochemically nonreactive. IgA, IgG, secretory component, and light chains were shown, by immunofluorescence, to be present in washed, pooled plaque sediment. Release of these immunoglobulins by urea treatment indicated their probable participation in immune complexes.

Albumins↗

PubMed1990

A proteolytic enzyme secreted by Proteus mirabilis degrades immunoglobulins of the immunoglobulin A1 (IgA1), IgA2, and IgG isotypes.

Proteus mirabilis strains associated with human urinary tract infections have previously been shown to secrete an extracellular metalloproteinase which cleaves serum immunoglobulin A (IgA). The enzyme has now been purified to apparent homogeneity from culture supernatants of P. mirabilis 64676. The protease activity is associated with a 50-kilodalton (kDa) protein. Unlike that of the classic IgA1 proteases, the substrate specificity of the P. mirabilis protease has been found to extend to both sublcasses of IgA, IgG, and the nonimmunoglobulin substrates, secretory component and casein. Cleavage of IgA1 and IgA2 by the P. mirabilis protease yielded fragments on sodium dodecyl sulfate-polyacrylamide gel electrophoresis whose sizes were consistent with a cleavage site outside the hinge region. Both secretory IgA1 and IgA2 were also cleaved by P. mirabilis protease, although the secretory IgA2 molecule was less readily cleaved than secretory IgA1. Free and IgA-bound secretory components were degraded to some extent by P. mirabilis protease. Cleavage of IgG, however, occurred at the hinge region as a two-stage process. The first stage was pepsinlike and generated an F(ab')2 fragment of 120 kDa and a small pFc fragment detected on nonreduced polyacrylamide gels. In the second stage, the F(ab')2 product was cleaved to yield papainlike Fab and Fc fragments, visualized as a diffuse band of 40 to 50 kDa.

Chromatography↗

PubMed1985

Syringocystadenoma papilliferum. A plasmacytotropic tumor.

Seven cases of syringocystadenoma papilliferum were studied by immunohistochemical methods for the presence of IgG, IgA, IgM, and secretory component in tumor epithelial cells and IgG, IgA, and IgM in plasma cells underlying the tumor epithelium. Six of seven cases showed IgA positivity within epithelial cells, one case showed faint intraepithelial IgG staining, and none stained for IgM. Four of five cases were positive for secretory component. The plasma cells were predominantly of the IgG and IgA class. These findings suggest that the association of plasma cells with this tumor is a consequence of epithelial attraction via a mechanism similar to that utilized by glands of the normal secretory immune system.

Adenoma, Sweat Gland↗

PubMed1986

Deletion of the cytoplasmic domain of the polymeric immunoglobulin receptor prevents basolateral localization and endocytosis.

We deleted the cytoplasmic domain of the polymeric immunoglobulin receptor. When expressed in fibroblasts, the truncated receptor, like the wild-type, reaches the cell surface, can bind ligand, and is cleaved to secretory component. Unlike the wild-type, it is not endocytosed. When expressed in polarized Madin-Darby canine kidney cells, the mutant receptor is transported from the Golgi apparatus directly to the apical surface and cleaved to secretory component. In contrast, the wild-type receptor travels from the Golgi to the basolateral surface and is then endocytosed and sent to the apical surface. These results suggest that the cytoplasmic domain of the receptor is necessary for both basolateral localization and endocytosis.

Animals↗

PubMed1992

Elevation of fibronectin levels in lung secretions of infants with respiratory distress syndrome and development of bronchopulmonary dysplasia.

To determine whether the level of fibronectin in lung secretions correlates with the severity of lung injury or with the development of bronchopulmonary dysplasia, or both, serial tracheal aspirate samples were collected from 32 preterm infants with severe respiratory distress syndrome. Levels of total fibronectin, cellular fibronectin, plasma fibronectin, albumin, and secretory component of IgA (SC) were determined for the first 1 to 2 weeks of life in the 14 infants who recovered without pulmonary sequelae, and for weeks 1 to 4 in the 18 infants in whom bronchopulmonary dysplasia developed. Secretory component was chosen as the reference protein because its concentration in lung secretions is minimally influenced by capillary leak and does not vary with gestational or postnatal age. Albumin/SC and plasma fibronectin/SC ratios in tracheal aspirates were significantly higher (p less than 0.05) during the first 2 weeks of life in infants in whom bronchopulmonary dysplasia developed, suggesting greater capillary permeability in these infants. Cellular fibronectin/SC ratios in aspirates from infants with bronchopulmonary dysplasia were also significantly higher in the first 2 weeks, 9.0 +/- 1.7 and 7.4 +/- 2.0 micrograms/microgram SC in weeks 1 and 2, respectively, in comparison with values from infants without bronchopulmonary dysplasia, 1.6 +/- 0.4 and 1.1 +/- 0.8 micrograms/microgram SC (p less than 0.01), suggesting increased synthesis of fibronectin in the lungs of infants with subsequent bronchopulmonary dysplasia. Elevated levels of both plasma and cellular fibronectin in tracheal aspirate samples may provide an early index of the severity of lung injury in infants with severe respiratory distress syndrome.

Albumins↗

PubMed2002

Induction of secretory pathway components in yeast is associated with increased stability of their mRNA.

The overexpression of certain membrane proteins is accompanied by a striking proliferation of intracellular membranes. One of the best characterized inducers of membrane proliferation is the 180-kD mammalian ribosome receptor (p180), whose expression in yeast results in increases in levels of mRNAs encoding proteins that function in the secretory pathway, and an elevation in the cell's ability to secrete proteins. In this study we demonstrate that neither the unfolded protein response nor increased transcription accounts for membrane proliferation or the observed increase in secretory pathway mRNAs. Rather, p180-induced up-regulation of certain secretory pathway transcripts is due to a p180-mediated increase in the longevity of these mRNA species, as determined by measurements of transcriptional activity and specific mRNA turnover. Moreover, we show that the longevity of mRNA in general is substantially promoted through the process of its targeting to the membrane of the endoplasmic reticulum. With respect to the terminal differentiation of secretory tissues, results from this model system provide insights into how the expression of a single protein, p180, could result in substantial morphological and functional changes.

Bodily Secretions↗

PubMed1991

Metabolic labeling of Dirofilaria immitis third- and fourth-stage larvae and their excretory-secretory products.

Infective third-stage larvae of Dirofilaria immitis were collected from Aedes aegypti and cultured in vitro to the fourth stage. Larval proteins were labeled metabolically using [35S]cysteine and methionine in different media and for different lengths of time. Labeled proteins in the excretory-secretory component and the larval homogenates were evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing and nonreducing conditions and by 2-dimensional gel electrophoresis. Numerous proteins ranging from 14 to greater than 200 kDa were identified from both the excretory-secretory components and the larval homogenates. Both fractions demonstrated shared and unique proteins. Using timed labeling, age- and stage-specific proteins were identified; at least 2 proteins of approximately 20.5 and 22 kDa were associated in time with the molt from the third to fourth stage. Two proteins of the same molecular weight were specifically recognized by immune dog sera, but not by sera of their infected nonimmune cohorts.

Animals↗

PubMed1983

Experimental IgA nephropathy in bile duct ligated rats.

Polymeric IgA and polymeric IgA-containing immune complexes are transported from blood to bile through hepatocyte-bound secretory component. In order to investigate interruption of this transport and its effect on the glomerulus, Sprague-Dawley rats underwent bile duct ligation. Renal tissue obtained at the time of sacrifice was stained by immunofluorescent techniques with antibodies to IgG, IgM, and IgA, and secretory component (SC) and C3. A progressive selective increase in the staining intensity of the glomerular mesangium was observed for IgA, C3, and SC in bile duct ligated rats. These changes were paralleled by a rise in serum IgA and C3. These findings are consistent with the view that glomerular deposition of IgA, C3, and SC in bile duct ligated rats may result from impairment of normal handling of polymeric IgA and polymeric IgA-containing immune complexes.

Animals↗

PubMed1995

Regulation of polymeric immunoglobulin A receptor messenger ribonucleic acid expression in rodent uteri: effect of sex hormones.

Previously we have shown that estradiol stimulates the production of secretory component, the external domain of the polymeric immunoglobulin A (IgA) receptor (pIgR) responsible for transporting IgA from tissues into secretions. In the present study, levels of pIgR messenger RNA (mRNA) in uterine tissues of rats were correlated with pIgR expression in epithelial cells and secretory component in uterine secretions. Analysis of uterine pIgR mRNA and pIgR expression in epithelial cells during the estrous cycle indicated that levels were high at proestrus and estrus and low at diestrus. When ovariectomized rats were treated with estradiol for 3 days, and pIgR mRNA was measured 4 and 12 h after the last injection, levels of uterine pIgR mRNA were significantly greater than those in saline-treated controls. High levels of pIgR were also detected in uterine epithelial cells and uterine secretions. When estradiol and progesterone were given in combination, progesterone partially reversed the effect of estradiol on pIgR mRNA levels and expression of pIgR in epithelial cells. These studies demonstrate that changes in uterine pIgR mRNA levels correlate with pIgR expression during the estrous cycle and in response to estradiol and progesterone. These findings suggest that mucosal immune responses in the reproductive tract are regulated in part by the actions of estradiol and progesterone on pIgR mRNA expression.

Animals↗

PubMed1977

Selective transport of an oligomeric IgA into canine saliva.

Evidence is presented which shows that an oligomeric IgA myeloma protein possessing J-chain but lacking secretory component, is selectively transferred from serum into canine saliva. The data also demonstrate that 125I-label remains with the IgA during the transfer process. These data interpreted in the light of findings in humans support the concept that the oligomeric form of IgA, devoid of secretory component, is required to achieve selective transport.

Animals↗

PubMed1996

Morphogenesis of inclusion bodies of urothelial carcinoma: a case study.

The morphogenesis of inclusions of urothelial carcinoma (K. Donhuijsen et al.: Hum Pathol 23:860, 1992) is described in a case of a 51-year-old man with poorly differentiated urothelial carcinoma. Peritoneal fluid preparations contained numerous dyscohesive, large, anaplastic cells with abundant dense amphophilic cytoplasm often compartmentalized into multiple, variably sized, intracytoplasmic lumina, each containing "bull's eye"-like inclusions, with a periodic acid Schiff-positive refractile central core and an alcian blue/mucicarmine-positive rim. Ultrastructurally, the progression of osmiophilic substance from membrane-bound exocrine-type secretory granules, via exocytosis, to a presence in both intracytoplasmic lumina and extracellular space has been documented. Immunohistochemically, the periodic acid Schiff-positive refractile cores, as well as the minute periodic acid Schiff-positive granules in the cytoplasm, stained positively for secretory component and peanut agglutinins, whereas the alcian blue-positive mucinous material, which coated the refractile cores as well as the lining of the intracytoplasmic lumina, stained strongly for epithelial membrane antigen and leu M1. Ultrastructurally, protein A-gold probes, immunolabeled for peanut agglutinin and secretory component, were localized to the osmiophilic substance.

Carcinoma, Transitional Cell↗

PubMed1984

[Analysis with immunofluorescence of antibodies attached to bacteria in urinary sediment in the diagnosis of the site of urinary infections].

The authors assess the sensitivity and specificity of the antibody-coated bacteria assay for the localization of urinary tract infections. The results are compared with those obtained from cultures of urine samples taken from the upper tract either by ureteral catheterization or by direct puncture of the renal pelvis. In upper urinary tract infections the research of total immunoglobulins has proven positive in 71.4% of the cases; of the IgA class in 71.4%; of the IgG class in 57.1%; of the IgM class in 28.6% and of the secretory component of IgA in 60% of the patients. In case of lower urinary tract infections the research of total immunoglobulins was positive in 25% of the cases: that of the IgA class in 8.3%; of the IgG in 25%; of the IgM in 25% and of the secretory component of IgA in 22.2% of patients.

Diagnosis, Differential↗

PubMed1989

Spontaneous expression of a low affinity Fc receptor for IgA (Fc alpha R) on human B cell lines.

Expression of receptors for IgA (Fc alpha Rs) was investigated on a panel of 35 human B cell lines by labelling with human secretory IgA (0.5 mg/ml) and flow cytometry analysis after staining with fluoresceinated goat anti-human secretory component and/or anti-alpha chain F(ab')2 fragments. Receptors for IgA could be demonstrated on one out of nine Burkitt's lymphoma cell lines, three out of five myeloma cell lines and five out of 21 lymphoblastoid cell lines. The percentage of Fc alpha R-positive cells within the same B cell line varied upon repeated examination. Human dimeric IgA1 lambda myeloma protein revealed the same number of IgA receptor positive cells as did secretory IgA, whereas monomeric IgA did not bind to Fc alpha R. Detection of Fc alpha R was not inhibited when the tests were carried out in the presence of human dimeric IgG, IgM, asialo-orosomucoid, and secretory component but it was abrogated by pre-treatment of the cells with trypsin. The binding characteristics of Fc alpha Rs were studied on the myeloma cell line Esteve, using 125I-labelled human dimeric IgA and secretory IgA. The binding was dose-dependent with rapid kinetics and specific inhibition by unlabelled secretory IgA. Scatchard plot analysis resulted in an equilibrium constant K ranging from 3.2 to 4.7 x 10(6) M/l. No correlation was observed between Fc alpha R expression and differentiation stage, monoclonality, polyclonality of the cell lines, or Ig class produced by the B cells.

Antibody Affinity↗

PubMed1996

IL-4 and IFN-gamma synergistically increase total polymeric IgA receptor levels in human intestinal epithelial cells. Role of protein tyrosine kinases.

IL-4 and IFN-gamma increase release of secretory component (SC), the polymeric IgA (plgA)-binding segment of the plgA receptor (plgAR), by the human intestinal epithelial cell line HT29. Moreover, these two cytokines synergistically increase plgA binding and cell surface staining for the receptor. To understand better the mechanism by which these cytokines regulate plgAR, we did quantitative immunoblotting using Abs against secretory component. We found that synergy occurs at the level of total cellular plgAR. Additionally, time course studies indicated that maximal receptor levels required >24-h incubation, that reaching maximal levels required at least 18 h of cytokine treatment, and that receptor levels remained elevated as long as cytokines were present. Conversely, if cytokines were removed, then cellular plgAR levels decreased with an approximate t1/2 of 20 h. Finally, synergy required the simultaneous presence of both cytokines throughout the treatment period. Direct measurement of second messengers and inhibitor studies suggest that Ca2+, cAMP, protein kinase A, and protein kinase C do not play major roles in regulating cellular plgAR levels by either cytokine, and do not contribute to the mechanism of synergy. In contrast, protein tyrosine kinase inhibitors potently inhibited all cytokine-dependent increases in total cellular plgAR. These results suggest that IL-4 and IFN-gamma increase cellular plgAR levels in HT29 cells predominantly by activating protein tyrosine kinase-dependent signaling pathways.

Blotting, Western↗

PubMed1982

Hormonal control of the secretory immune system of the human uterine cervix.

A quantitative immunohistochemical study of IgA-containing plasma cells in the human uterine cervix has shown that the number of such cells increases during the late secretory phase of the menstrual cycle but decreases in the early secretory phase of the cycle, in pregnancy, in cystic glandular hyperplasia of the endometrium and after the menopause. These results are interpreted as indicating that progesterone causes an increased plasma cell localisation in the cervix whilst oestrogens cause a decrease: it is suggested that this reflects hormonal control of a receptor mechanism and that this receptor can also be blocked by high levels of LH or hCG. The number of cervical epithelial cells containing secretory component (SC) is increased in the late secretory phase of the menstrual cycle, in users of contraceptive pills and in pregnancy. It is suggested that progesterone acts to increase the intra-epithelial content of SC and that no other hormonal factor need be involved.

Aging↗

PubMed1999

Developmental changes of sugar occurrence and distribution in the rat submandibular and sublingual glands.

The developmental expression of salivary glycoconjugates was investigated in the rat submandibular and sublingual glands by conventional and lectin histochemistry. By the time of the first differentiation of secretory structures, in spite of similar morphological features, a different histochemical reactivity was detected, accounting for a relevant content of neutral glycoconjugates in the submandibular gland and the occurrence of both neutral and acidic glycoconjugates in the sublingual one. The use of lectins allowed the main changes of secretory components to be noted around gestational day 18. DBA and WGA lectins seemed to act as pre- and post-natal development markers while Con A lectin was indicative of post-natal differentiation. Taken together, data from lectin histochemistry indicated the transitional occurrence of glycoconjugates, probably involved in temporally restricted functions, as well as the co-existence of different secretory components that might also reflect maturational changes of single products.

Acetylgalactosamine↗

PubMedDate not supplied

[Interaction of oligonucleotides and ATP with preparations of sIgA possessing protein kinase activity].

Interaction of secretory immunoglobulins A of a varying degree of purity with oligonucleotides and ATP has been studied by the method of affinity modification. For this aim we used reactive derivatives of 32P-labeled deoxyoligonucleotide (ClRCH2NHp(T)14) and [gamma-32P]ATP (ClR-32PppA) or ATP (ClR-pppA) bearing a 4-[(N-2-chloroethyl-N-methyl)amino]benzylamine residue. Preparations of sIgA were obtained from human milk by sequential chromatography on protein A-sepharose (P1), DEAE-fractogel (P2) and by gel-filtration in 50 mM NaOH (P3). It was revealed, that the H- and L-chains of sIgA P1; H-, L-chains and secretory component (SC) in sIgA P2 and only SC in sIgA P3 were exposed to modification after incubation with ClRCH2NHp(T)14. LPS, DNA, tRNA, heparin, sufficiently inhibited the modification of chains of sIgA P1. These competitors did not influence the modification of H- and L-chains of sIgA P2, but DNA, tRNA, heparin, inhibited binding of SC with the modifier. Suppressing affect of binding of ClRCH2NHp(T)14 with secretory component of sIgA P3 by d(T)14 has been observed as well. The research of ClR-32PppA interaction with sIgA P3 has shown that H- and L-chains of sIgA are exposed to modification. ATP inhibited the reaction. Study of the influence of modification on the protein kinase activity of sIgA P3 has revealed, that the preliminary incubation of sIgA P3 with ClR-pppA leads to inhibition of protein kinase activity. We suggest that sIgA, possessing the protein kinase activity (sIgA-abzymes) has an ATP-binding center (catalytic center) and has an oligonucleotide-binding center as well.

Adenosine Triphosphate↗

PubMed1992

Ontogeny of immunity to oral microbiota in humans.

This article reviews the ontogeny of immune systems in the human oral cavity that may influence the colonization, accumulation, or pathogenesis of oral microbiota. The prenatal development of cellular components associated with the secretory immune system reveals that the initial organization of tissue into Peyer's patches can first be detected immunohistologically at 11 weeks gestation. Epithelial cells positive for secretory component and immunocytes positive for IgM can be detected in salivary gland tissue by 19 to 20 weeks and continue to predominate during gestation. After birth, immunocytes containing IgA begin to dominate. Essentially, no IgA can be detected in saliva at birth. However, salivary IgA and IgM often appear soon thereafter, presumably in response to environmental antigenic and mitogenic challenges. Salivary IgA in young infants has molecular characteristics of secretory IgA and becomes the quantitatively predominate Ig in saliva. Both IgA subclasses are present in proportions characteristic of adult pure glandular salivas in many 1- to 2-month-old infants, although the appearance of IgA2 is delayed in some subjects. Many innate, antibody, and cellular immune components are found in maternal colostrum and breast milk. The antibacterial properties of these maternal factors are diverse and can exert multifaceted protective effects on the infant's alimentary tract. The infant apparently can mount mucosal immune responses quite early in life. For example, salivary antibody activity to organisms that originally colonize the gut (e.g., E. coli) or the oral cavity (e.g., S. mitis, S. salivarius) can be detected by 1 to 2 months of age. Most of this antibody activity has characteristics of secretory IgA, although some IgM antibody can also be initially detected. Salivary IgA1 and IgA2 antibody specificities to S. mitis and S. salivarius components increase qualitatively and quantitatively during the first few years of life. Salivary IgA antibody to components of streptococci that require hard surfaces for colonization (e.g., S. sanguis and mutans streptococci) generally appear after tooth eruption. The loss of placentally derived maternal IgG antibody specificities to these microbiota in the circulation is replaced by de novo synthesis, presumably as a result of the teething process. These IgG antibodies can enter the oral cavity in the gingival crevicular fluid and by the process of teething.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗