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At least 811 records · Page 45Linked to original sources
PubMed1985

An immunocytochemical study on secretory mechanism of IgA in human pancreas.

To analyze the secretory mechanism of immunoglobulins into pancreatic secretion, pancreatic juice IgA was measured by single radial immunodiffusion and characterized immunochemically, and immunoglobulins, J chain and secretory component (SC) were localized immunocytochemically in pancreatic tissues by the peroxidase-labeled antibody method. The concentration of IgA was 0.0225 mg/ml with a range of 0.010 to 0.049. IgA associated with SC was demonstrated immunochemically in three cases. IgA, SC and J chain were demonstrated immunocytochemically in the pancreatic duct epithelium with the features characteristic of endocytic, SC-mediated transfer of IgA. The results of the present study suggested that transfer of IgA linked by J chain and SC across ductal epithelial cells, but not acinar cells occurred in human pancreas.

Biological Transport↗
PubMed1984

Role of dietary iron in maturation of rat small intestine at weaning.

The weanling process is characterized by the transition from a liquid diet poor in iron (rat milk) to a solid diet high in iron (chow pellets). To examine the effects of iron content of the weanling diet on terminal maturation of rat small intestine, suckling pups, nursed by iron-sufficient mothers, were weaned by day 16 onto a solid basal diet that was either deficient [low-iron diet (LID): 0.5 mg iron/100 g solid] or high [high-iron diet (HID) controls: 30 mg iron/100 g solid] in iron. The animals were studied during or at the end of the 4th postnatal wk. By day 17 rats weaned onto the LID exhibited an initial rise in jejunal sucrase activity as did their controls, but the activity plateau of the enzyme was reduced to a level 60% of the controls. On day 28 iron-deprived rats were anemic and showed significant decreases (P less than 0.01 compared with HID rats) in the activity of jejunal sucrase (-57%), neutral lactase (-83%), and maltase (-46%), whereas villus height, crypt depth, mucosal mass parameters, ileal acid beta-galactosidase activity, mucosal protein, and DNA synthesis rates were equivalent in LID and HID groups. The concentration of the secretory component, a glycoprotein synthesized by the intestinal crypt cell, was markedly depressed (P less than 0.01 vs. controls) in the jejunum (-54%) and ileum (-79%) of iron-deprived rats. When D-[1-14C]glucosamine was injected intraperitoneally, incorporation of the label into jejunal and ileal brush-border proteins was two to three times lower for iron-deficient rats than for controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Immunohistochemical study of carcinoembryonic antigen, epithelial membrane antigen, and secretory immunoglobulin system in the large bowel adenoma-carcinoma sequence.

To identify parameters for the malignant potential of large bowel adenomas, we used the avidin-biotin-peroxidase complex (ABC) technique. Patterns of carcinoembryonic antigen, epithelial membrane antigen, IgAs, and secretory component in 31 tubular, tubulovillous, and villous adenomas with different grading of dysplasia (mild, moderate, severe) and with early cancer were studied. All markers showed different degrees of staining intensity and various cellular localizations. We found that these variations might be related to dysplasia grading. Adenoma size did not influence the marker patterns. IgAs seemed to be the more selective among the markers studied. Our results suggested a dysplasia-carcinoma sequence instead of an adenoma-carcinoma sequence concept.

Adenocarcinoma↗
PubMed1980

Neoplastic human colon cells in studies on the translocation of dimeric IgA.

The translocation of dimeric IgA across epithelial cells was studied by immunoelectron microscopy in an in vitro system with cultured neoplastic human colon cells (HT-29). Ultrastructurally, the cells were found to be well-polarized epithelial cells connected by intercellular junctions. Secretory component (SC) was localized to the basolateral plasma membranes. Dimeric human IgA, when reacted with the cells at 0 C, bound selectively to SC. When incubated at 37 C, the bound dimeric IgA was internalized by pinocytosis and transported apically through the cytoplasm in vesicles. The vesicles were opened to the lumen at the apical surfaces or discharged into the lumen. We conclude that the translocation of dimeric IgA across intestinal epithelial cells has been defined at the ultrastructural level in cultured neoplastic colon cells in vitro.

Biological Transport, Active↗
PubMed1977

Abnormalities of the local immune system in intestinal neoplasia: a morphological study.

In colonic adenocarcinomata abnormalities have been noted in all morphological aspects of the local immune system of the bowel; thus, in such tumours there is a defective production of secretory IgA, a diminished content of secretory component (SC) and a marked decrease in intraepithelial lymphocytes. By contrast, no such abnormalities were noted in the non-neoplastic areas of the bowel, either immediately adjacent to, or some distance from, the carcinoma. These findings suggest that there is not usually any generalised morphological abnormality of the local immune systems in intestinal neoplasia and that the immunological abnormalities noted within the tumour are a result of the changed nature of the epithelium, thus altering, or interfering with, the normal interactions between epithelial and lymphoid tissue in the gut.

Adenocarcinoma↗
PubMed1984

Reaction pattern of xenografted human salivary glands in nude mice. An immunohistological and autoradiographical study.

35 specimens of human parotid gland and 37 of submandibular gland were transplanted into athymic nude mice. At distinct time intervals, from 1 day to 8 months the transplants were collected and examined. The transplanted glands were studied by light microscopy, immunohistology and autoradiography. The following changes were detectable: acute injury to the xenograft and inflammatory reaction (day 1-7), regeneration of the transplant and the beginning of adaptation to the "mouse milieu" (day 8-30), completion of adaptation (day 30 and later). The presence of the following substances was analysed: amylase, lactoferrin, secretory component, tissue polypeptide antigen (TPA). Amylase was only detected in the early transplants. Lactoferrin was seen only in the small duct system. TPA was present during all transplantation periods and was quantitatively correlated with the 3H thymidine labeling index. From our observations we can say that the salivary glands show two different reacting compartments: a large and a small duct system. The histogenesis of the xenografts, and the relationships of the changes observed to human salivary gland diseases were discussed.

Amylases↗
PubMed1989

Intraepithelial lumina in urothelial bladder neoplasms. A histochemical, immunohistochemical and electron microscopy study.

Intraepithelial lumina observed in 12 urothelial bladder neoplasms were studied histochemically, immunohistochemically and ultrastructurally. Both intercellular and intracytoplasmic lumina could be demonstrated showing an alcianophilic margin and containing non-sulphated acid mucins. The presence of secretory component (SC) was identified in neoplastic urothelial cells around or adjacent to intercellular lumina as well as in cells with intracytoplasmic lumina. The cells surrounding intercellular lumina revealed ultrastructurally tight junctions, microvilli and a prominent glycocalyx while cellular remnants were found quite often within the lumen. As similar histochemical, immunohistochemical and ultrastructural characteristics are also expressed in surface umbrella cells of normal urothelium it is suggested that a focal differentiation of neoplastic urothelial cells towards surface umbrella-like cells takes place and that this process is intimately related to the formation of lumina.

Carcinoma↗
PubMed1977

[Secretory immunoglobulin A in the blood sera of healthy and ill persons].

Sera of healthy and sick persons were tested for the presence of secretory IgA (SIgA) and free secretory component (SC) SIgA was present in the blood of healthy persons in low concentrations (1.07 mg/100 mg), and free SC was absent. Infectious and somatic diseases, in which damage of the epithelial covering of the gastrointestinal and respriatory tracts was possible, were accompanied by increased blood SIgA content. There was also noted a distinct relationship between the blood SIgA concentration and the severity of infectious diseases and pneumonia supervention. In these cases the SIgA level proved to rise.

Adolescent↗
PubMed1992

Secretory immunoglobulins in serum from human immunodeficiency virus (HIV)-infected patients.

Infection by the human immunodeficiency virus is associated with polyclonal B cell activation and increased levels of serum IgA. In order to characterize the molecular species of serum IgA, we have measured total IgA, IgA1, and IgA2 in sera from 60 HIV-1-infected patients and 40 healthy controls. In addition, secretory IgA (S-IgA), secretory IgM (S-IgM), free immunoreactive secretory component (SC), and the distribution of monomeric and polymeric IgA were determined. The data confirm the elevation of total serum IgA levels in HIV-1-infected patients, and both IgA1 and IgA2 concentrations are elevated. Furthermore, the data show a substantial increase in serum levels of both monomeric and polymeric IgA. Serum S-IgA levels were significantly increased in CDC group II patients versus controls and more frequently elevated in CDC group IV patients. The highest S-IgA levels were found among patients with the lowest blood CD4+ cell counts. Serum S-IgA levels were not correlated with serum levels of either total IgA or polymeric IgA. Serum S-IgM levels were also increased in HIV-1-infected patients and positively correlated with serum S-IgA levels. Conversely, serum levels of free SC were not altered. An increase in serum S-IgA was not related to human hepatitis B virus infection and/or to hepatic dysfunction or to diarrhea or overt intestinal infection. The data indicate that secretory Ig (S-IgM and S-IgA), which are likely to be produced at mucosal sites, increase in the serum of HIV-1-infected patients.

Adult↗
PubMed1984

Histochemical studies of metaplastic lesions in the human gallbladder.

We studied goblet cell metaplasia and pseudopyloric gland metaplasia in 25 surgically removed, paraffin-embedded gallbladder specimens using mucin histochemistry, silver methods for endocrine cells, and the indirect immunoperoxidase method for 12 peptide hormones, secretory component, and lysozyme. Goblet cell metaplasia was closely related to the occurrence of endocrine cells that showed argentaffinity, argyrophilia, or immunoreactive gastrin, somatostatin, pancreatic polypeptide, or motilin. Mucosal areas without goblet cell metaplasia were devoid of such endocrine cells. Metaplastic pseudopyloric glands showing lysozyme immunoreactivity were positive for class III mucin with paradoxical concanavalin A staining. Specimens with florid metaplastic lesions revealed a low tendency to form Rokitansky-Aschoff sinuses whose cells never showed a metaplastic nature. We compared the pathophysiological significance of metaplastic lesions in the gallbladder with intestinal metaplasia of the stomach.

Endocrine Glands↗
PubMed1987

Analysis of serum and synovial fluid IgA in Reiter's syndrome and reactive arthritis.

The presumed antecedent infection which precedes Reiter's syndrome and reactive arthritis is frequently across a mucosal surface, and IgA immune responses may play a role in this process. Twelve of 29 patients with these conditions demonstrated elevation in serum IgA levels, and serum IgA levels in the postdysentery group (mean 3.21 g/liter +/- 1.27) were higher (P less than 0.01) than those in the posturethritis group (mean 2.40 g/liter +/- 0.80). In 10 of the 12 patients, IgA was the only immunoglobulin increased. There was no evidence of activation of complement in serum or synovial fluid. Using a complement-dependent assay, we were unable to demonstrate circulating IgA immune complexes. Sucrose density gradient ultracentrifugation analysis was used to assess IgA immune complexes in a non-complement-dependent manner. IgA of 11s was in fact demonstrated by this technique but appeared to be polymeric IgA on the basis of specific binding of secretory component and resistance to acid dissociation. IgA rheumatoid factor was not present. Synovial fluid revealed levels of polymeric IgA higher (mean 56.7% +/- 12.9) than did serum (23.7% +/- 13.9, P less than 0.001) despite higher levels of total IgA in serum than in synovial fluid (synovial fluid:serum ratio of IgA, mean 0.53 +/- 0.11). Although elevation in serum IgA in postdysenteric arthropathies suggests mucosal acquisition of antigen, the study does not implicate IgA circulating immune complexes in the pathogenesis of these diseases.

Antigen-Antibody Complex↗
PubMed1982

Abnormal topological distribution of surface glycoprotein on neoplastic epithelial cells.

Immunohistochemically, carcinoembryonic antigen (CEA) was found at the apex and secretory component (SC) on the basal lateral surface of normal colonic epithelial cells. On neoplastic colon cells, both glycoproteins when present were distributed all around the cells. Little or no CEA and SC were found on normal gastric epithelial cells. CEA and SC appeared on intestinal metaplastic cells in a pattern similar to that of the normal colonic epithelium. In gastric carcinoma, both glycoproteins when present were found all around the neoplastic cells. The observations suggest that neoplastic transformation of epithelial cells is accompanied by a loss of the normal polar distribution of surface glycoproteins.

Carcinoembryonic Antigen↗
PubMed1985

Charge and size of mesangial IgA in IgA nephropathy.

To characterize the physicochemical properties of the mesangial IgA in primary IgA nephropathy, acid-eluates from percutaneous renal biopsies of 20 patients were examined. The acid-eluates were obtained from 1287 +/- 498 glomerular sections. The IgA content (mean 15 +/- 10 ng) represented 0.4% of the total eluted proteins. To analyze the molecular weight and the charge of eluted IgA, 11 eluates were subjected to high pressure liquid chromatography (at pH 6.8 and/or pH 3.5) and five eluates to isoelectric focusing on agarose. IgA was detected in the fractions by an IgA-RIA. Comparison of the elution profiles at different pH showed a statistically significant decrease of the excluded IgA peak (greater than or equal to 1,000,000 daltons), and a significant increase of polymeric IgA peaks (1,000,000-320,000 and 320,000 daltons) in acidic chromatography, as compared to non-dissociating conditions. Under acidic conditions, polymeric IgA represent 64% of total eluted IgA. Secretory component binding to polymeric IgA was demonstrated in four out of eight eluates tested. The isoelectric point (pI) of eluted IgA ranged from 4.5 to 5.6, contrasting with the broader and more neutral pI of normal serum IgA (4.5 to 6.8). This study shows that the multimeric nature of IgA, the formation of IgA complexes, and the anionic charge of IgA are likely to be involved in the mesangial IgA deposition in idiopathic IgA nephropathy.

Adolescent↗
PubMed2004

Multiple cleavage sites for polymeric immunoglobulin receptor.

Human polymeric immunoglobulin receptor (pIgR) was expressed in baby hamster kidney (BHK) cells using a recombinant vaccinia virus transfection system. Cleavage of pIgR on the cell surface was partially inhibited by the proteinase inhibitor, leupeptin. We addressed the question whether some particular regions of pIgR could affect the efficient cleavage of this molecule, with the following results: (1) a mutant lacking the entire cytoplasmic region resulted in release of secretory component (SC) into the culture supernatant much faster than wild-type; (2) a pIgR mutant lacking the entire extracellular domain 6, the region containing the susceptible cleavage sites, could be cleaved and released as a mutant SC. The transport kinetics of this mutant between endoplasmic reticulum (ER) and Golgi or Golgi and the cell surface was equivalent to wild-type pIgR. Our results indicate that although the main cleavage site is in domain 6, at least one other cleavage site may exist.

Animals↗
PubMed1997

Production of secretory immunoglobulin A by a single mammalian cell.

Secretory IgA (sIgA) plays a critical role in providing protection against infection at the mucosal surfaces. Normally, sIgA is the product of two different cell types with heavy, light, and J chains produced by the plasma cells, whereas secretory component (SC), a cleavage product of the polymeric immunoglobulin receptor (pIgR), is added during the transit of dimeric IgA through the epithelial cell layer. In the current study, by introducing a gene for the processed form of SC into a cell line that produces dimeric IgA, we have succeeded in creating a single cell that is able to produce and secrete covalently joined sIgA. To our knowledge, this is the first time it has been possible to efficiently produce large quantities of sIgA of defined specificity in mammalian cells. The sIgA made using this approach has great potential as an immunotherapeutic.

Amino Acid Sequence↗
PubMed1998

Secretory IgA induces degranulation of IL-3-primed basophils.

We examined whether secretory IgA (sIgA), known to mediate eosinophil stimulation, has an effect on basophil functions. An immobilized preparation of sIgA, but not of monomeric IgA, induced histamine release (approximately 15% of total histamine contents) from human basophils in vitro. sIgA-induced basophil histamine release was totally dependent on pretreatment with IL-3. IL-5 and granulocyte-macrophage CSF also primed basophils for sIgA-mediated release. Exogenous divalent ions, i.e., Ca2+ and Mg2+, were essential for sIgA-mediated basophil degranulation, and the degranulation was completed within 45 min. A newly synthesized lipid mediator, leukotriene C4, was also liberated from IL-3-primed, sIgA-stimulated basophils. Enzyme digestion experiments revealed that the (Fc)2 x secretory component portion of sIgA is important for sIgA-mediated basophil activation, but the functional binding sites of sIgA on basophils were surmised to be different from FcalphaR. These observations reveal the novel finding that sIgA is able to stimulate basophils as well as eosinophils. Since sIgA is the most abundant Ig isotype in the secretions from mucosal tissues, and basophils are active participants in allergic late-phase reactions, sIgA-mediated basophil mediator release is potentially involved in exacerbation of the inflammation associated with allergic disorders.

Basophils↗
PubMed1990

Value of immunohistochemical demonstration of several epithelial markers in hyperplastic and neoplastic endometrium.

The distribution of prekeratin, vimentin, epithelial membrane antigen (EMA), and secretory component (SC) was demonstrated immunohistochemically in 31 patients with adenomatous hyperplasia (AH), 12 patients with atypical adenomatous hyperplasia (AAH), and 39 patients with endometrial carcinoma. Prekeratin was presented in 94% of AHs, 92% of AAHs, and 87% of adenocarcinomas. Vimentin was detected in 68% of AHs, 50% of AAHs, and 37% of adenocarcinomas, showing decreased expression as the lesion progressed to malignancy (P less than 0.05). EMA was detected in 26% of AHs, 67% of AAHs, and 95% of adenocarcinomas (P less than 0.001). SC demonstrated focal and weak expression in 29% of AHs, but showed increased staining intensity in 67% of adenocarcinomas (P less than 0.01). Well-differentiated tumors expressed SC better than poorly differentiated tumors (P less than 0.01). All markers showed a heterogeneous staining pattern and, for a given histologic hyperplastic or neoplastic state, corresponded to several phenotypes. In conclusion, prekeratin seems to be a good marker for epithelial differentiation in hyperplastic endometrium, and EMA is a good marker in neoplastic endometrium. In hyperplastic lesions, the loss of vimentin expression in the absence of secretory changes gives rise to suspicions regarding their benign process. Also, EMA can help in distinguishing between hyperplastic and neoplastic states, while detection of SC may be of help in more precise grading of endometrial carcinoma.

Adenocarcinoma↗
PubMedDate not supplied

The secretory immunoglobulin system in urothelial neoplasia.

The role of the secretory immunoglobulin system in urinary tract neoplasia has been investigated by staining formalin-fixed, paraffin-wax embedded sections of normal and abnormal urinary tract epithelium for secretory component (SC), IgA and J (joining) chain. Normal mucosa contains IgA with J chain and SC as a thin superficial layer on surface umbrella cells and in small amounts in the cytoplasm of intermediate cells. Inflamed mucosa is infiltrated by many IgA and J chain positive plasma cells in the lamina propria and there is IgA, SC and J chain in the cytoplasm of the second layer of the epithelium as much as in surface umbrella cells. Epithelium with moderate to severe dysplasia and invasive transitional cell carcinoma is almost always negative, containing only occasional cells with cytoplasmic IgA, J chain and SC, whilst surface staining is entirely absent.

Humans↗