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PubMed1995

Generation and assembly of secretory antibodies in plants.

Four transgenic Nicotiana tabacum plants were generated that expressed a murine monoclonal antibody kappa chain, a hybrid immunoglobulin A-G heavy chain, a murine joining chain, and a rabbit secretory component, respectively. Successive sexual crosses between these plants and filial recombinants resulted in plants that expressed all four protein chains simultaneously. These chains were assembled into a functional, high molecular weight secretory immunoglobulin that recognized the native streptococcal antigen I/II cell surface adhesion molecule. In plants, single cells are able to assemble secretory antibodies, whereas two different cell types are required in mammals. Transgenic plants may be suitable for large-scale production of recombinant secretory immunoglobulin A for passive mucosal immunotherapy. Plant cells also possess the requisite mechanisms for assembly and expression of other complex recombinant protein molecules.

Amino Acid Sequence↗
PubMed1997

Mucosal immunity--a major adaptive defence mechanism.

The epithelial glycoprotein called secretory component (SC) is quantitatively the most important receptor of the immune system because it is responsible for external transport of locally produced polymeric IgA (pIgA) to generate remarkably large amounts of secretory IgA. Antibodies of this type constitute the major mediators of specific humoral immunity. Transmembrane SC belongs to the Ig supergene family and functions as a common pIg receptor, also translocating pentameric IgM externally to form secretory IgM. The B cells responsible for mucosal pIg production are initially stimulated in organized mucosa-associated lymphoepithelial structures, particularly the Peyer's patches in the distal small intestine; from these inductive site they migrate as memory cells to exocrine tissues all over the body. Mucous membranes are thus furnished with secretory antibodies in an integrated way, ensuring a variety of specificities at every secretory effector site. There is currently great interest in exploiting this integrated or "common" mucosal immune system for oral vaccination against pathogenic infectious agents and also to induce tolerance in T cell-mediated autoimmune diseases. However, much remains to be learned about mechanisms for antigen uptake and processing necessary to elicit stimulatory or suppressive mucosal immune responses. Moreover, evidence is emerging for the existence of considerable regionalization with regard to functional links between inductive sites and effecter sites of mucosal immunity.

Animals↗
PubMed1983

[Immunoelectron microscopic localization of CEA in gastrointestinal malignancies].

Immunoperoxidase techniques were used to localize carcinoembryonic antigens (CEA) and secretory component (SC) in normal and abnormal human colonic, gastric and biliary tract mucosae. CEA was found on the microvillous surface of normal colonic cells, but not in biliary tract epithelial cells. However, little or no CEA and SC were found on normal gastric epithelial cells. On intestinal metaplastic cells, both antigens were present in a pattern similar to that of the normal colonic epithelium. Gastric and colonic adenoma cells showing severe dysplasia occasionally failed to maintain polar expression of both glycoproteins on the cell surface. In adenocarcinoma, this polar distribution was absent, and both glycoproteins were found all around the neoplastic cells as previously reported in colonic and gastric neoplasia. These observations suggest that deviations from normal differentiation and maturation, such intestinal metaplasia and adenoma of the gastrointestinal and biliary tract mucosa, are recognizable by alterations in the cell-surface distribution of CEA and SC, and neoplastic transformation of the epithelial cells may be accompanied by a loss of the normal polar distribution of surface membrane components.

Adenoma↗
PubMed1982

[Estimation of secretory immunoglobulin A in serum of pregnant women (author's transl)].

Secretory immunoglobulin A (S-IgA) was measured by means of radial immunodiffusion, according to Mancini, with a self-made antiserum to the secretory component being used together with a S-IgA standard. S-IgA serum concentrations went up with significance in the course of pregnancy, which was probably attributable to increased production of secretory protein in the breasts in preparation for lactation.

Female↗
PubMed2006

Human ceruminous gland: ultrastructure and histochemical analysis of antimicrobial and cytoskeletal components.

The ceruminous glands in the skin of the human external auditory canal are modified apocrine glands, which, together with sebaceous glands, produce the cerumen, the ear wax. Cerumen plays an important role in the protection of the ear canal against physical damage and microbial invasion. We studied the morphology of the glandular cells by light and electronmicroscopy. Antimicrobial and cytoskeletal components of the ceruminous glands were investigated by immunohistochemical methods. Numerous antimicrobial proteins and peptides are present in the ceruminous glandular cells: beta-defensin-1, beta-defensin-2, cathelicidin, lysozyme, lactoferrin, MUC1, secretory component of IgA. These data indicate a crucial role in the innate host defense against diverse pathogens. The apocrine secretion mechanism is a special mode of secretion by which the apical part of the cell cytoplasm surrounded by a membrane is pinched off. We could show that the presence of actin filaments, CK 19 and CK 7, seems to play a role in the pinching-off mechanism. Finally, we showed the secretion of lipid vesicles from the ceruminous gland. We could extend the number of detected antimicrobial peptides and proteins in human ceruminous glandular cells that protect the surface of the external auditory meatus. In addition, we detected proteins involved in the apocrine secretion mode of the ceruminous gland.

Adolescent↗
PubMedDate not supplied

The local immunological defence system of the human endometrium.

The distribution of immunoglobulins and secretory component (SC) in the human endometrium has been studied by an immunoperoxidase technique. SC is present in a proportion of the epithelial cells and the amount of this substance is increased during the secretory phase of the cycle. A variety of immunoglobulins are present, in low concentrations, in the stromal interstitium during the secretory phase of the cycle and these are thought to diffuse passively from the plasma as a non-specific accompaniment of stomal oedema. Only IgA is found in the epithelial cells and this appears solely in those cells containing SC. No immunoglobuln-containing lymphoid cells are present in the endometrium. It is suggested that the endometrium lacks a true local secretory immune system but is able, because of its content of SC, to compensate for this by extracting polymeric IgA from the plasma. This system presumably helps to protect the endometrium against infection but the biological significance of its apparent control by progesterone is uncertain.

Animals↗
PubMed1990

[Central and peripheral type small cell carcinoma of the lung--histologic, immunohistochemical, and clinical analyses].

In 17 cases of resected small cell carcinoma of the lung, there were 4 cases of central type and 13 cases of peripheral type. Histologic subtypes were classified into oat cell carcinoma (OAT), intermediate cell type (INT), and small cell carcinoma with large cell component (SC/LC). SC/LC was divided according to the criteria of Radice et al. Immunohistochemically, gastrin-releasing peptide (GRP) and neuron specific enolase (NSE) were used as markers for neuroendocrine cells, and keratin and secretory component (SC) were used as markers for epithelial and gland epithelial cells, respectively. Histologically, 4 cases of the central type were divided into 3 cases of INT and one case of SC/LC. Thirteen cases of the peripheral type were divided into 3 cases of OAT, 6 cases of INT, and 4 cases of SC/LC. SC/LC was more frequently seen in the peripheral type than in the central type. Immunohistochemically, there was no difference in the frequency of positive staining for GRP and NSE between the central and peripheral types, but positive staining for keratin and SC were more frequent in the peripheral type than in the central type. Three cases who survived more than 3 years were histologically divided into two cases of INT and one case of SC/LC. Immunohistochemically, these 3 cases showed positive staining for GRP or NSE, but also showed positive staining for keratin or SC. Our results showed that some of the peripheral type small cell carcinoma of the lung had histologic and immunohistochemical features which were different from those of typical small cell carcinoma. Long survival time after resection in some of the peripheral cases might be due to these features.

Aged↗
PubMed1981

Inhibition of the pokeweed mitogen-induced response of normal peripheral blood lymphocytes by humoral components of colostrum.

Colostral whey at dilutions up to 1 : 100 inhibited both the uptake of tritium-labelled thymidine and the differentiation of pokeweed mitogen-stimulated peripheral blood lymphocytes from normal adults into immunoglobulin-containing plasma cells. Upon gel filtration (Sephadex G-200), inhibitory activity was associated with high molecular weight fractions. Secretory component, but not monomeric, polymeric or colostral IgA, IgM, IgG, lactoferrin, casein or alpha-lactalbumin, inhibited the response to mitogen. Supernatants from cultures of colostral cells did not induce the differentiation of adult peripheral or cord blood lymphocytes into IgA-containing cells and did not stimulate the uptake of tritium-labelled thymidine.

Cell Differentiation↗
PubMed1988

Is there any tubular secretion of protein?

Immunohistological investigations performed with the PAP method on tubular casts in the thick Henle loops and in the distal convoluted tubules led to the following results. 1) In control kidneys, casts consisting of sIgA and IgM occur, mostly isolated, in 30% and 20%, respectively, of cases. On the other hand IgG casts, likewise isolated, are only observed in 7% of cases. 2) In the case of mesangioproliferative glomerulonephritis of the IgA and non-IgA nephritis type, casts consisting of sIgA and IgM are observed more often than in control kidneys, especially when the serum creatinine concentration exceeds 1.3 mg%; i.e., the glomerular filtration is reduced. 3) In kidneys with inflammatory and non-inflammatory glomerular diseases which had led to nephrotic syndrome, casts consisting of sIgA and IgM are not observed more often than in kidneys with glomerulonephritides which had not been accompanied by nephrotic syndrome. 4) In kidneys with severe impairment of the excretory function (rapidly-progressive glomerulonephritis, primary malignant nephrosclerosis, acute renal failure) casts consisting of sIgA and IgM are observed more often than in controls but not more often than in IgA and non-IgA nephritides with increased serum creatinine concentration. 5) In kidneys which had become aglomerular as a result of scarring of the glomeruli, with atrophic proximal tubules and preserved epithelia of the ascending loop of Henle, casts consisting of sIgA and IgM as well as secretory component occur in a large quantity.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1985

Localization of prostatic basic protein ("probasin") in the rat prostates by use of monoclonal antibody.

Isolated nuclei of the rat prostates contain a unique androgen-dependent basic protein, "probasin". Despite that it was hardly detectable in the cytosol centrifugally prepared from the prostates, immunofluorescent histological analysis of whole tissues using monoclonal antibody, which was raised against probasin purified from the nuclei, revealed that probasin was abundantly localized in the lumen and acinal regions of the epithelium, but hardly in the nuclei. Previous extraction of secretory fluid from the prostates caused about 60% decrease in the probasin content of isolated nuclei. These suggest that probasin was originally a secretory component in the prostates, being redistributed from the secretory fluid and granule into nuclei during fractionation of subcellular components.

Androgen-Binding Protein↗
PubMed1987

Evidence for the presence of lactoferrin in odontogenic keratocyst fluids.

Investigations into the possibility that X (an antigen consistently present in aspirated odontogenic keratocysts, but not in most fluids from other cyst types), represented a keratinocyte component failed to identify the antigen as a keratin, involucrin, or one of the blood group substances. Antigen X was detected in human mixed and parotid saliva and in colostrum, as well as in a commercially obtained preparation of colostral IgA. The antigen was similar biochemically to both secretory component and lactoferrin but proved to be identical antigenically with lactoferrin. The origin of lactoferrin in keratocyst fluids remains uncertain, though the lining epithelium seems a more likely source than does the very variable, and often negligible, inflammatory infiltrate found in these lesions.

Antigens↗
PubMedDate not supplied

The role of the liver in translocation of IgA into the gastrointestinal tract.

The liver plays a key role in the translocation of IgA into the upper gastrointestinal tract. The amount of IgA transported and the mechanisms involved, however, vary widely among species. In some, best defined in the rat, large amounts of polymeric IgA (pIgA) are cleared from the plasma by hepatocytes, which synthesize the polymeric immunoglobulin receptor, secretory component (SC), and express it on their sinusoidal plasma membranes. Circulating pIgA binds to SC, is internalized into endocytic vesicles and transported across the hepatocyte to the bile canalicular membrane, where the pIgA is released into bile in complex with a portion of the SC, i.e., secretory sIgA (sIgA). In some other species, including man, there is much less hepatic transport of circulating IgA, at least in part because SC is present only in biliary epithelium, and there is relatively more local synthesis of IgA within hepatobiliary tissues. On the other hand, certain IgA1 myeloma proteins appear to bind to and enter human hepatocytes via an asialoglycoprotein receptor. These species differences have implications for the biological significance of the biliary secretion of IgA, including the disposal of circulating IgA-antigen complexes into bile.

Animals↗
PubMed1977

Multiple myeloma, IgA cryoglobulinemia and serum hyperviscosity in a dog.

Clinical signs of hyperviscosity syndrome in a 6-year-old dog included listlessness, polydipsia, anorexia, vomiting, and recurrent bleeding from the gums. Fundoscopy showed the typical retinal changes associated with this syndrome. A polymeric IgA cryoglobulin characterized in the dog's serum was later isolated and structurally studied. It was found to contain J chain but no secretory component. The heavy and light chains were covalently bound.

Animals↗
PubMed1979

The distribution and localization of immunoglobulin in the gastric mucosa and gastric cancer.

The distribution and localization of immunoglobulin in the gastric mucosa and gastric cancer were studied by means of immunofluorescence. In the lamina propria of the stomach, like the other parts of the gastrointestinal tract, IgA producing cells predominated, but their population density varied from case to case. The main portion of secretion of IgA in the stomach was deep foveolar epithelium. IgA containing epithelial cells in the stomach were much less than those in the intestine, but they increased with advancement of intestinal metaplasia. Some gastric cancer cells retained the ability of secretory component production and took up IgA in their cytoplasm.

Antibody-Producing Cells↗
PubMed1983

Serum and secretory IgA immune response to Klebsiella pneumoniae in ankylosing spondylitis.

Serum and salivary IgA antibodies to Klebsiella pneumoniae were estimated by enzyme-linked immunosorbent assay (ELISA) in 53 patients with ankylosing spondylitis (AS) and 30 healthy controls. The concentrations of total serum IgA, salivary secretory component (SC) and serum C-reactive protein (CRP) were also measured. In the serum of AS patients there was a positive correlation between Klebsiella IgA antibodies and the CRP. Salivary anti-Klebsiella IgA was elevated in 39% of AS patients although this was not associated with disease activity. Serum and secretory IgA antibodies to E. coli and Pseudomonas aeruginosa were similar in patients and controls irrespective of disease activity. We conclude that part of the increase in salivary and serum IgA in AS may be due to a specific immune response to Klebsiella in the gastrointestinal tract and that serum antibodies reflect more closely those events associated with active inflammatory disease.

Adult↗
PubMed1986

Secretory piece and IgA deficiency in a patient with Waldenstrom's macroglobulinemia.

A case of a patient suffering from Waldenstrom's macroglobulinemia who developed diarrhea and mild steatorrhea is described. Laboratory studies revealed low serum IgA, intestinal secretory IgA deficiency, and small intestine bacterial overgrowth as demonstrated by the C14-cholylglycine breath test. These findings suggest that selective IgA deficiency and secretory component deficiency may be contributing factors in the development of diarrhea in Waldenstrom's macroglobulinemia.

Aged↗
PubMed2000

Macromolecular organization of saliva: identification of 'insoluble' MUC5B assemblies and non-mucin proteins in the gel phase.

Stimulated human submandibular/sublingual (HSMSL) and whole saliva were separated into sol and gel phases and mucins were isolated by density-gradient centrifugation in CsCl/4M guanidinium chloride. MUC5B and MUC7 were identified using anti-peptide antisera raised against sequences within the MUC5B and MUC7 apoproteins respectively. MUC7 was found mainly in the sol phase of both HSMSL and whole saliva, but some MUC7 was consistently present in the gel phase, suggesting that this mucin may interact with the salivary gel matrix. In HSMSL saliva, MUC5B was found in the gel phase; however, most of the material was 'insoluble' in guanidinium chloride and was only brought into solution by reduction. In whole saliva, the MUC5B mucin was present both in the sol and gel phases although some material was again 'insoluble'. Rate-zonal centrifugation of whole saliva showed that MUC5B mucins in the sol phase were smaller than those in the gel phase, suggesting differences in oligomerization and/or degradation. Antibodies against IgA, secretory component, lysozyme and lactoferrin were used to study the distribution of non-gel-forming proteins in the different phases of saliva. The majority of these proteins was found in the sol phase of both HSMSL and whole saliva. However, a significant fraction was present in the gel phase of whole saliva, suggesting a post-secretory interaction with the salivary gel matrix. A monoclonal antibody against a parotid salivary agglutinin was used to show that this protein is present mainly in the gel phase of both whole saliva and parotid secretion.

Agglutinins↗
PubMedDate not supplied

[A comparative analysis of the effect of clofelin on gastric secretory function in man and dog].

It is established that clofelin suppresses the human and dog insulin gastric secretion as well as human basal and histamine secretion. Clofelin has no effect on the secretory function of the dog stomach, stimulated by pentagastrin, carbachol histamine. It is supposed that clofelin-induced suppression of the human histamine gastric secretion takes place due to the inhibition of basal secretory component being a part of the common secretory effect on histamine. Clofelin may be promising drug in the treatment of patients with hypertension and duodenum ulcer.

Adolescent↗