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Human Peyer's patches: lympho-epithelial relationships and characteristics of immunoglobulin-producing cells.

Human Peyers patches (PP) were studied by immunohistochemistry to characterize functional properties of the follicle-associated epithelium (FAE) including the "membrane" (M) cells. The FAE had no transporting capacity for polymeric IgA (pIgA) because it did not express the secretory component (SC) which acts as a pIgA receptor. However, it expressed MHC class II (HLA-DR) determinants, except for the M cells (which were tentatively identified by absence of brush border alkaline phosphatase). It is possible, therefore, that the FAE generally performs class II-restricted transport and presentation to T cells of antigens which have been adequately processed in the gut lumen. The function of M cells may be limited to transport of particulate or undegraded antigens to subjacent macrophages for processing and subsequent presentation. There were significantly more intra- and subepithelial T cells in PP than in distant villi, and the T cells were concentrated adjacent to M cells. The proportion of the CD4+ phenotype (putative helper T cells) was much higher in FAE (approximately 40%) than in villous epithelium where the CD8+ (putative suppressor) phenotype predominated strikingly (approximately 90%). This disparity might reflect differences in capacity for positive and negative immune regulation at the two sites. The B cells terminating with Ig production in PP and adjacent to solitary lymphoid follicles apparently belonged to relatively mature memory clones as they showed a large proportion of IgG immunocytes and reduced J-chain expression. Conversely, both IgG and IgA immunocytes in lamina propria (LP) showed a high percentage of J-chain positivity (80-100%); such positivity was also considerable (45-60%) in mesenteric lymph nodes (MLN) in contrast to peripheral lymph nodes (PLN) and palatine tonsils (PT). Moreover, there was a decreasing percentage of IgA2 immunocytes in the order of PP (52%), distant ileal LP (40%), MLN (32%), PLN (11%), and PT (5%). Taken together, our results suggested that dissemination of relatively immature memory B-cell clones with high J-chain expression takes place from PP through MLN and that preferential settlement of such clones occurs in LP.

Antibody-Producing Cells↗

Effect of sialodacryoadenitis virus exposure on acinar epithelial cells from the rat lacrimal gland.

Sialodacryoadenitis virus (SDAV), a RNA coronavirus, induces degenerative, necrotic and atrophic alterations in acinar epithelial cells of the rat lacrimal gland. To begin to explore the underlying mechanism(s) of this viral effect, we sought in the present study to: (1) determine whether SDAV invades and replicates in lacrimal gland acinar cells in vitro and (2) assess whether short-term SDAV challenge interferes with the viability or function of acinar cells in vitro. For comparison we also evaluated the relative infectivity of SDAV in acinar epithelial cells from lacrimal, submandibular and parotid glands, given that salivary tissues are known to be highly susceptible to SDAV infection in vivo. Acinar epithelial cells from lacrimal, submandibular or parotid glands were isolated from male rats, exposed briefly to SDAV or control cell antigen and then cultured for four, eight or twelve days. At experimental termination, SDAV titers in both media and sonicated cell extracts were evaluated by plaque assay titration on mouse L2 cell monolayers. To evaluate functional aspects of lacrimal gland acinar cells, SDAV-infected cells were incubated in the presence or absence of dihydrotestosterone and culture media were analyzed by RIA to measure the extent of the androgen-induced increase in secretory component (SC) production. Our results showed that: (1) SDAV invades and replicates in lacrimal gland acinar cells, Viral challenge resulted in a significant, time-dependent increase in SDAV titers, that were primarily cell-associated and greatly exceeded amounts contained in the original inoculum; (2) SDAV infection did not compromise lacrimal acinar cell viability or prevent the cellular SC response to androgens. Viral presence, though, did often attenuate the magnitude of this hormone action; and (3) SDAV infects salivary acinar cells, but the kinetics and magnitude or viral replication in lacrimal, submandibular and parotid cells showed considerable variations. These findings demonstrate that SDAV invades and replicates in acinar epithelial cells from lacrimal and salivary glands. The resulting release of infectious progeny may play a role in the SDAV-induced pathology of exocrine tissues in vivo.

Animals↗

A new protein with a particular thermoprecipitability in bovine milk.

A new protein with a particular thermoprecipitability was isolated from bovine milk and tentatively termed milk pyroglobulin. The protein which was soluble at a relatively cold temperature was precipitated by raising the temperature to a certain degree depending on the concentration of the protein. The precipitate disappeared on recooling. This protein had the electrophoretic mobility of gamma globulin but did not carry either antigenic specificities of immunoglobulins or of free secretory component. The molecular weight was estimated to be approximately 60,000 in thin-layer gel filtration on Sephadex G-200 superfine gel, but the protein appeared to be convertible to molecules with a lower molecular weight of approximately 20,000 in the presence of bovine serum albumin. The presence of the albumin inhibited the thermoprecipitation as did alpha-lactalbumin but not IgG immunoglobulin from bovine colostrum. In SDS-polyacrylamide gel electrophoresis, the protein was separated into two components having a molecular weight of 19,000 and 10,000, respectively. Both components were thermoprecipitable and carried identical antigenic determinants.

Animals↗

The humoral activity of the avian thymic microenvironment.

The thymic microenvironment (composed of the lymphoepithelial stroma and the secretory products of the thymic epithelium) provides the required milieu for the development of the thymus-derived lymphocytes (T cells). There is limited information characterizing or identifying the active secretory components of the avian thymus. The work discussed here has focused on examination of the presence, regulation, and activity of one of the thymic hormones (thymulin) in the chicken. A thymulin-like product has been shown to exist in chicken serum as assessed by the mammalian bioassay and an ELISA immunoassay; thymectomy removes this product from the serum. Serum thymulin activity has been shown to be directly related to the thyroid status of the chick with the functionally hypothyroid Cornell sex-linked dwarf strain having lower levels than the euthyroid K strain. Alterations in circulating thymulin concentrations produced by daily thymulin injections resulted in an altered profile of the major peripheral blood T cell subpopulations and produced significant changes in the autoimmune pathology present within the Obese strain chicken. These approaches represent preliminary attempts to study the role of thymulin in avian immune development and in immune-neuroendocrine interactions.

Animals↗

Vesicular localization and characterization of a novel post-proline-cleaving aminodipeptidase, quiescent cell proline dipeptidase.

A large number of chemokines, cytokines, and signal peptides share a highly conserved X-Pro motif on the N-terminus. The cleavage of this N-terminal X-Pro dipeptide results in functional alterations of chemokines such as RANTES, stroma-derived factor-1, and macrophage-derived chemokine. Until recently, CD26/DPPIV was the only known protease with the ability to cleave N-terminal X-Pro motifs at neutral pH. We have isolated and cloned a novel serine protease, quiescent cell proline dipeptidase (QPP), with substrate specificity similar to that of CD26/DPPIV. In this paper we show that QPP, like CD26/DPPIV, is synthesized with a propeptide and undergoes N:-glycosylation. Interestingly, this glycosylation is required for QPP enzymatic activity, but not for its localization. Unlike the cell surface molecule, CD26/DPPIV, QPP is targeted to intracellular vesicles that are distinct from lysosomes. Proteinase K treatment of intact vesicles indicates that QPP is located within the vesicles. These vesicles appear to have a secretory component, as QPP is secreted in a functionally active form in response to calcium release. The presence of QPP in the vesicular compartment suggests that molecules bearing the N-terminal X-Pro motif can be cleaved at multiple sites within and outside the cell. These results expand the potential site(s) and scope of a process that appears to be an important mechanism of post-translational regulation.

Amino Acid Sequence↗

J chain in the nurse shark: implications for function in a lower vertebrate.

J chain is a small polypeptide covalently attached to polymeric IgA and IgM. In humans and mice, it plays a role in binding Ig to the polymeric Ig receptor for transport into secretions. The putative orthologue of mammalian J chain has been identified in the nurse shark by sequence analysis of cDNA and the polypeptide isolated from IgM. Conservation with J chains from other species is relatively poor, especially in the carboxyl-terminal portion, and, unlike other J chains, the shark protein is not acidic. The only highly conserved segment in all known J chains is a block of residues surrounding an N-linked glycosylation site. Of the eight half-cystine residues that are conserved in mammalian J chains, three are lacking in the nurse shark, including two in the carboxyl-terminal segment that have been reported to be required for binding of human J chain-containing IgA to secretory component. Taken together with these data, the relative abundance of J chain transcripts in the spleen and their absence in the spiral valve (intestine) suggest that J chain in nurse sharks may not have a role in Ig secretion. Analysis of J chain sequences in diverse species is in agreement with accepted phylogenetic relationships, with the exception of the earthworm, suggesting that the reported presence of J chain in invertebrates should be reassessed.

Amino Acid Sequence↗

Mucosal B cell deficiency in IgA-/- mice abrogates the development of allergic lung inflammation.

We have investigated the consequence of lack of IgA on host immunity using a murine model of allergic lung inflammation. Mice with a targeted disruption of the alpha-switch region and 5' H chain gene (IgA(-/-) mice), which lack total IgA, developed significantly reduced pulmonary inflammation with fewer inflammatory cells in lung tissue and bronchoalveolar lavage fluids, as well as reduced levels of total and IgG1 OVA-specific Abs and decreased IL-4 and IL-5 in bronchoalveolar lavage fluids compared with IgA(+/+) controls, following allergen sensitization and challenge. This defect was attributable to fewer B cells in the lungs of IgA(-/-) mice. Polymeric IgR-deficient (pIgR(-/-)) mice, which lack the receptor that transports polymeric IgA across the mucosal epithelium where it is cleaved to form secretory IgA, were used to assess the contribution of secretory IgA vs total IgA in the induction of allergic lung inflammation. pIgR(-/-) and pIgR(+/+) mice had comparable levels of inflammation, demonstrating that IgA bound to secretory component is not necessary for the development of allergic lung inflammation, although this does not necessarily rule out a role for transudated IgA in lung secretions because of "mucosal leakiness" in these mice. The results indicate that Ag-specific B cells are required at mucosal surfaces for induction of inflammation and likely function as major APCs in the lung for soluble protein Ags.

Administration, Intranasal↗

Characterization of humoral immune response in the serum and bile of patients with opisthorchiasis and its application in immunodiagnosis.

The humoral immune response in patients with opisthorchiasis was investigated using an enzyme-linked immunosorbent assay. IgG antibody reactive with Opisthorchis viverrini antigens was present in the serum of all patients. The infection also stimulated specific IgA and IgE antibody responses in most patients and, in practically all patients, there was a marked increase of total IgE. There was a moderate but significant correlation between serum IgG antibody level and severity of infection as judged from the quantity of eggs in the stool of the patients. There was also a significant elevation of antibody in the bile and serum of O. viverrini-infected patients who also had biliary obstruction. Analysis of paired samples from individual patients showed that while IgG was the predominant class of antibody in the serum of all patients, IgA was present at approximately the same level as IgG or higher in the bile of many patients. In addition to IgA and IgG antibodies, IgE antibody was also detectable in 50% of the bile samples. The high level of IgA antibody in the bile together with its presence in association with the secretory component suggested a selective transport and/or local production of IgA antibody by the hepatobiliary system of these patients.

Animals↗

[The effect of L-arginine on the ultrastructure of atrial cardiomyocytes in experimental hypercholesterolemia].

The results of electronmicroscopic study of the right atrium in experimental hypercholesterolemia revealed a disturbance of ultrastructural organisation of both cardiomyocytes and endothelial cells of blood microvessels. Intake of L-arginine--a precursor of synthesis of nitric oxide (NO)--with atherogenic diet was found to prevent to some extent the damage of ultrastructural organisation of cardiomyocytes and to stimulate the production of atrial granules. A significant number of secretory components, which differ in terms of structure and function, revealed in the endothelium of blood microvessels may testify to the fact that upon administration of L-arginine the paracrine effect of hormonal regulation is enhanced manifesting itself through an increase of synthesis and secretion of natriuretic hormone in atrial cardiomyocytes. A tissue hormonal system is displayed through an increase of synthesis and secretion of atrial natriuretic hormone in cardiomyocytes. On the other hand, a NO precursor L-arginine may produce a correcting effect upon the ultrastructure of endotheliocytes in hypercholesterolemia.

Animals↗

Fine specificity of ligand-binding domain 1 in the polymeric Ig receptor: importance of the CDR2-containing region for IgM interaction.

The human polymeric Ig receptor (pIgR), also called transmembrane secretory component, is expressed basolaterally on exocrine epithelia, and mediates specific external transport of dimeric IgA and pentameric IgM. The extracellular part of pIgR consists of five Ig-like domains (D1-D5), and a highly conserved D1 region appears to mediate the initial noncovalent ligand interaction. While the human pIgR binds both dimeric IgA and pentameric IgM with high affinity, the rabbit counterpart has virtually no binding capacity for pentameric IgM. This remarkable disparity constitutes evidence that the binding site of the two ligands differs with regard to essential receptor contact elements. Therefore, we expressed human/rabbit chimeric pIgRs in Madin-Darby canine kidney cells and found that human pIgR D1 is crucial for the interaction with pentameric IgM when placed in the context of a full-length receptor regardless of its backbone species. D1 contains three complementarity-determining region-like loops (CDR1-3), and to further map human D1 regions involved in pentameric IgM binding, we transfected Madin-Darby canine kidney cells with human/rabbit chimeric receptors in which the regions containing the CDR-like loops had been interchanged. Our results showed that the region containing the CDR2-like loop is the most essential for pentameric IgM binding. The region containing the CDR1-like loop also contributed substantially to this interaction, whereas only little contribution was provided by the region containing the CDR3-like loop, although it appeared to be necessary for maximal pentameric IgM binding.

Amino Acid Sequence↗

Characteristics of mesenteric lymph node cells homing to gut-associated lymphoid tissue in syngeneic mice.

A subpopulation of cells in murine mesenteric lymph nodes, about 15% of those synthesizing DNA at any given time, homes specifically to the gut and mesenteric nodes of syngeneic recipients within 1 day of i.v. transfer. In contrast, cells from Oeyer's patches or peripheral lymph nodes do not. A large proportion of the B blasts which home to the small intestine has surface Ig, but lacks complement receptors. Thy-1-positive T blasts home to the gut to a lesser extent than B blasts. However, it is probable that equal fractions of B and T blasts home to mesenteric nodes. Homing is not affected by measures calculated to interfere with the combination of cell surface IgA and secretory component.

Animals↗

[Immune and nonimmune variants of acute pancreatitis].

The article gives an analysis of humoral immunity to structural and secretory components of the pancreas in acute pancreatitis. Based on the distinctions revealed the authors determined two variants of the disease--the immune and nonimmune variants which is of great significance in diagnostics and treatment of acute pancreatitis, for the administration of immunocorrecting medicines in particular.

Acute Disease↗

[The state of antigen-dependent immunity system in children with chronic tonsillitis].

245 children aged 7-14 years with decompensated chronic tonsillitis were examined and treated in Anapa health resort. Before therapy the children had subnormal concentration of CD3+, CD4+/CD8+, elevated absolute and relative concentration of CD16+, low concentration of salivary IgA and SIgA combined with high serum IgM. The treatment brought a positive trend in the above indices, but CD16+, serum IgA and salivary SIgA remained higher than in controls. This may be explained by genetic predisposition of some children (primary defects of IgA and its secretory component synthesis), effects of autoimmune pathology, natural reaction to persistent viral infection.

Adolescent↗

Uterine serous papillary carcinoma clinical and immunopathological study of 9 cases.

From January 1993 to December 1998, nine patients with serous papillary endometrial carcinoma (SPEC) were diagnosed and treated at the 2nd Department of Obstetrics and Gynecology, Areteion University Hospital. The incidence of SPEC in our Clinic was 6.77%. The mean age of patients was 65.5 years (range 54-82 years). All patients underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy and epiploectomy. Abdominal and para-aortic lymph node sampling was performed in all cases and peritoneal washings were examined cytologically. Histological sections of the specimens, stained with haematoxylin-eosin, were retrieved from the Laboratory of Pathology and re-evaluated by two pathologists. All cases conformed to the diagnostic criteria for SPEC. Immunohistochemical studies were performed in paraffin blocks retrieved from the files, by a streptavidin-viotin method for the detection of vimentin (ENZO monoclonal ab), secretory component (DAKO polyclonal ab), CEA (DAKO monoclonal ab), EMA (DAKO monoclonal ab). The hormonal receptor status, assessed by appropriate positive and negative controls, was studied as well. The presence of mucin and glycogen was studied by histochemical reaction, PAS, PAS diastase and mucicarmine. Serous papillary carcinoma is an unusual but distinct type of endometrical adenocarcinoma, a non-hormonal dependent tumor, with aggressive biologic behavior. Its recognition is mandatory for a correct therapeutic approach.

Aged↗

[Electrochemical studies of induced secretion of catecholamines from individual vesicles of rat chromaffin cells].

Influence of agents inducing secretion: KCl-induced membrane depolarization and acetylcholine on catecholamine secretion from individual vesicles of rat chromaffin cells was studied by using amperometric methods. It has been shown that secretory components participating in these processes are different. An importance of cellular response on different kind of stimulation is discussed.

Animals↗

Investigation of saliva immunoglobulins in monoclonal gammopathies.

Salivary immonoglobulins of patients with multiple myeloma, lymphoid leukaemia, agammaglobulinaemia and of normal healthy adults were examined. Higher IgG level was identified in 4 cases IgG monoclonal gammopathy. In these cases extremely large quantities of IgG monoclonal protein were transmitted from serum into salivary secretions. On the basis of the results it appears that monoclonal IgA is transferred to external secretions in patients with IgA monoclonal gammopathy. High IgM level was found in both serum and saliva of agammaglobulinaemic patients. "IgM secretory component" complex could be identified in saliva. In lymphoid leukaemic patients the salivary immunoglobulins presented normal values except of a patient whose tigA lacked in serum and also in saliva.

Agammaglobulinemia↗

Early events of experimental exposure to amorphous and crystalline silica in the rat: time course of surfactant protein D.

Pneumoconioses determined by chronic inhalation of different kinds of silica present with peculiar clinical and histopathological features. Silicosis, caused by crystalline silica, is characterized by typical fibrous parenchymal nodules. Less defined are pneumoconioses due to amorphous silica. Aim of current experimental research on silicosis is to investigate the early events that lead to nodular fibrosis of the lung. A secretory component of the pulmonary environment, surfactant, seems to be involved in silica toxicity; surfactant protein D is a protein constituent, apparently involved in the homeostasis of the phospholipid component. We studied the behaviour of SP-D 2, 12 and 24 hours after treatment with 200 mg/kg crystalline silica or pumice powder suspended in 400 microl/kg saline solution and instiled intratracheally to rats. Both immunohistochemical localization and immunoblotting quantification demonstrated a sensible increase in intracellular SP-D, localized in alveolar type II cells and some bronchiolar epithelial cells, 2 hours after treatment. Increment appears less marked 12 hours after administration, reaching again levels comparable to control at 24 hours. The behaviour of SP-D after pumice instilation is similar, but with a significantly minor increment at 2 hours. These results indicate crystalline silica as responsible for a stronger acute injury of pulmonary tissue.

Animals↗