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J P Vaerman

Publications and source records attributed to J P Vaerman.

At least 55 records · Page 3Linked to original sources
PubMed1994

Fc alpha-receptor expression on the myelomonocytic cell line THP-1: comparison with human alveolar macrophages.

Immunoglobulin A (IgA) and alveolar macrophages are two important components of the immune system in the respiratory tract. Fc alpha-receptors (Fc alpha R) are present on neutrophils, eosinophils and a series of human mononuclear phagocytes, including monocytes, alveolar macrophages and leukaemia cell lines (U-937). In the present study, using idiotypes and anti-idiotypic antibodies, we report that THP-1 cells, a myelomonocytic cell line, constitutively express Fc alpha R and that all IgA preparations used bind the receptor. Of the stimuli used (phorbol myristate acetate, retinoic acid, calcitriol), only calcitriol can induce differentiation of THP-1 cells, as assessed by CD14 expression. The expression of Fc alpha R appears to be independent of cell differentiation, since calcitriol pretreatment has no effect on IgA-binding. Finally, My43, a monoclonal antibody recognizing the Fc alpha R on U-937 cells, does not bind to THP-1 cells or to human alveolar macrophages. In addition, preincubation of THP-1 cells or human alveolar macrophages with My43 does not diminish IgA-binding to these cells. Ribonucleic acid (RNA) encoding the Fc alpha R isolated from U-937 is expressed, although possibly at a lower level, in alveolar macrophages and THP-1 cells. In conclusion, Fc alpha R are constitutively expressed on THP-1 cells and share some characteristics with the Fc alpha R described in human alveolar macrophages. THP-1 cells, therefore, may represent a reasonable model for further investigation of the interaction of immunoglobulin A and tissue macrophages.

Base Sequence↗
PubMed1994

Neuroendocrinimmune modulation of secretory component production by rat lacrimal, salivary, and intestinal epithelial cells.

PURPOSE: To evaluate the kinetics, receptor specificity, molecular basis, and site selectivity of the endocrine and neural regulation of secretory component (SC) synthesis by rat lacrimal gland acinar cells. METHODS: Acinar cells from the rat lacrimal and submandibular glands, as well as epithelial cells (IEC-6) from the rat small intestine, were cultured in supplemented, serum-free media and treated with dihydrotestosterone, cholera toxin, carbachol, vehicle, or other agents for varying time periods. Media SC levels were measured by radioimmunoassay. RESULTS: The authors' findings with lacrimal gland acinar cells demonstrate that: a significant, temporal delay exists between the initiation of stimulatory or inhibitory signals and the eventual cellular SC response to regulatory compounds; the parasympathetic analogue, carbachol, exerts a dual effect on SC output, i.e., an early stimulation (hours) followed by an extended suppression (days); the androgen and cholinergic control of SC is receptor-mediated; and the androgen modulation of SC may involve the induction of gene expression. In addition, the authors' results show that distinct, tissue-specific variations occur in the nature of SC regulation: Compounds that control SC output by lacrimal acinar cells do not necessarily alter SC production by epithelial cells from the rat submandibular gland or small intestine. CONCLUSIONS: These findings advance the authors' understanding of the neuroendocrine regulation of SC synthesis in acinar cells from the lacrimal gland. Moreover, the authors' results indicate that the nature of the neural, endocrine, and immune control of lacrimal SC may be unique.

Animals↗
PubMed1994

Disulfide bond formation between dimeric immunoglobulin A and the polymeric immunoglobulin receptor during hepatic transcytosis.

The polymeric immunoglobulin receptor on rat hepatocytes binds dimeric IgA on the sinusoidal surface and mediates its transport to the canaliculus, where the complex of dimeric IgA and secretory component, the cleaved extracellular domain of polymeric immunoglobulin receptor, is secreted into bile. This process is unique in that disulfide bonds are formed between dimeric IgA and polymeric immunoglobulin receptor during transcytosis, permanently preventing their dissociation. Here we present three lines of evidence that disulfide bonding between dimeric IgA and polymeric immunoglobulin receptor occurs predominantly in a late transcytotic compartment and that hepatic transcytosis can proceed in the absence of disulfide bond formation. First, throughout the course of transcytosis the percentage of intracellular dimeric IgA disulfide bonded to polymeric immunoglobulin receptor is less than half that in bile, suggesting that disulfide bond formation is a late event in transcytosis. Second, dimeric IgA that recycles from early endocytotic compartments into the circulation is mostly noncovalently bound to secretory component. Finally, the rate of transcytosis of dimeric IgA and its appearance in bile are not affected when disulfide bond formation with polymeric immunoglobulin receptor is inhibited by blocking of free thiol groups on dimeric IgA with iodoacetamide. These results are consistent with other findings in the literature and indicate that the main physiological role of disulfide bond formation between dimeric IgA and polymeric immunoglobulin receptor is not to facilitate transcytosis but, rather, to stabilize the dimeric IgA-secretory component complex after its release into external secretions such as bile and intestinal secretions.

Animals↗
PubMed1993

Alpha-chain disease: analysis of alpha-chain protein and secretory component in jejunal fluid.

BACKGROUND: It is unclear why different forms of alpha-chain disease protein appear in intestinal fluid. This was studied in a 23-year-old Mauritanian man in whom alpha-chain disease was diagnosed localized to the duodenum and jejunum, nasopharynx, and bone marrow. METHODS: The duodenal infiltrate was studied by immunohistochemistry. Forms of alpha chain-containing proteins in serum and jejunal fluid were analyzed by ultracentrifugation and radioimmunoassays. RESULTS: The infiltrating cells contained alpha-1 chain but no light chains, and approximately 66% showed variable expression of J chain. Serum contained a large fraction of monomeric alpha-chain disease protein, whereas both monomeric and heavier forms appeared in jejunal fluid. Some of the latter were bound to secretory component, and the fluid contained virtually no free component. CONCLUSIONS: Linkage of polymeric alpha-chain disease protein to secretory component depends on balanced synthesis of alpha chains and J chain in the proliferating B cells, giving rise to polymers with binding site for secretory component expressed as an epithelial receptor. Insufficient receptor-mediated transport capacity (either relative and/or because of intestinal crypt reduction) results in passive external transfer of polymers without bound secretory component along with leakage of serum-derived or locally produced monomeric alpha-chain disease protein, the latter presumably originating from immunocytes with little or no J-chain synthesis.

Adult↗
PubMed1993

Influence of severe protein malnutrition on rat lacrimal, salivary and gastrointestinal immune expression during development, adulthood and ageing.

The objective of the present study was to examine and to compare the impact of severe protein malnutrition during development, adulthood and ageing on secretory immune expression in the eye, mouth and small intestine. In addition, we sought to determine whether potential abrogation of mucosal immunity by protein deprivation might be reversed by the administration of a balanced diet. Weanling, adult and aged rats were provided isocaloric diets containing 24% (control), 19%, 14%, 10%, 6% and/or 3.2% protein levels for defined periods and various immunological parameters were evaluated before, during and after the dietary regimen. Our results demonstrated the following. (1) Severe protein malnutrition (3.2%) dramatically suppressed the secretory immune system in eyes of weanling rats. After 8 weeks of protein insufficiency, tear IgA concentrations in young rats had undergone a precipitous decrease, such that IgA could not be detected in tears. This response was paralleled by a significant decline in the tear volume, tear secretory component (SC), IgG and total protein content, number of IgA-containing cells in lacrimal tissue, as well as the amounts of SC and/or IgA in saliva, intestinal secretions and serum. In contrast, the immunological effects of protein malnutrition in adult or aged animals varied considerably depending upon the specific mucosal site. (2) The influence of protein deprivation was dose dependent and reversible: maintenance of weanling rats on 10%, 6% or 3.2% protein diets interfered with the establishment of ocular and intestinal mucosal immunity, but later administration of optimal diets to these malnourished animals permitted a rapid immune recovery. (3) The impact of protein malnutrition on tear IgA levels in weanling animals, as shown by pair-feeding experiments, appeared to reflect primarily protein deficiency and not caloric restriction. Overall, these findings show that dietary protein plays a significant, site-specific role in the developmental expression of the secretory immune system.

Aging↗
PubMed1993

An interspecies idiotope associated with the anti-cholera toxin response detected by a monoclonal auto-anti-idiotypic antibody.

We have produced an auto-anti-idiotypic (auto-anti-id) monoclonal antibody (mAb) which reacted with syngenic mouse polyclonal anti-cholera toxin (anti-CT) IgG antibody (Ab) and six/eight different anti-CT IgG mAb, but not with normal mouse BALB/c IgG. The binding of this auto-anti-id mAb on one anti-CT mAb was significantly inhibited by polyclonal anti-CT sera of rats, rabbits and mice. Thus the idiotope on anti-CT Ab recognized by this auto-anti-id mAb was public and expressed in different species. Because of the absence of competition between CT and this auto-anti-id mAb for the binding to the six anti-CT mAb, the anti-id mAb was classified as an Ab2 alpha. The efficiency of this auto-anti-id mAb to induce anti-CT Ab3 was tested with success in rabbits and rats. Auto-anti-id mAb-immunized rats were significantly protected against an intraintestinal CT challenge.

Animals↗
PubMed1992

Modulation of oral tolerance to ovalbumin by cholera toxin and its B subunit.

Oral administration to mice of ovalbumin (OVA), if given together with cholera toxin (CT) or its B subunit (CTB) prevented the hyporesponsiveness to OVA subsequently injected parenterally. Oral immunization with CT plus OVA or OVA plus CTB in fact primed the immune system, inducing a stronger response to a subsequent parenteral injection of OVA with complete Freund's adjuvant than in mice prefed only with OVA or with saline. Oral CT plus OVA also induced good serum IgG1 and IgA anti-OVA responses, with slightly (not significant) decreased IgG2a and IgG2b responses. Our in vivo findings agree well with earlier in vitro data from others, including CT inhibition of the Th1 CD4+ T cell subset and with CT effect on B cells (induction of LPS-stimulated IgM+ B cells to undergo increased switch differentiation to IgG1- and IgA-secreting cells).

Adjuvants, Immunologic↗
PubMed1992

Ontogeny of the receptor for polymeric immunoglobulins in rat hepatocytes.

Based on in vitro experiments measuring daily secretion rates in the culture media of rat hepatocytes and in vivo experiments using pulse labeling of intracellular precursors, the present study examines the ontogenic expression of the polymeric immunoglobulin receptor and secretory component by hepatocytes during growth. Our data indicate that hepatocytes from infant and suckling rats (day 5, 15) cultured in serum-free and hormone-free conditions only secreted trace amounts of secretory component. Beginning on day 20, basal secretion rate showed a marked upsurge with a 10-fold increase by day 35. The addition of dexamethasone (10(-7) mol/L) to the culture media enhanced by 2.5-fold the basal secretion of secretory component by hepatocytes from 20-, 25-, and 35-day-old rats, while addition of insulin to the media had no effect. The response to dexamethasone was dose-dependent (10(-5), 10(-6), 10(-7) mol/L) and specific. In vivo pulse labeling of receptor precursors in hepatocytes from 40-day-old rats allowed the identification of three intracellular forms: a 105-kilodalton peptide and a 116-120-kilodalton mature doublet. In 13-day-old rats, three immature precursors were detected: a 105-kilodalton peptide and a high molecular weight doublet of 185-190 kilodaltons. Sucklings (13 days) treated with corticosterone showed a pattern of precursors similar to controls. These findings support the following conclusions: (a) hepatocytes from infant and suckling rats synthesize and process immature receptor precursors whose expression is unaffected by corticosterone treatment, and (b) active secretion of secretory component is initiated at weaning independently from humoral and hormonal factors while the magnitude of its production by the liver is under the control of glucocorticoids.

Aging↗
PubMed1992

Oral immunization against cholera toxin with a live Yersinia enterocolitica carrier in mice.

The 70-kb pYV plasmid of Yersinia enterocolitica directs the synthesis and secretion of several virulence determinants called Yops. These proteins are produced during the invasion of the host tissues and induce a strong antibody response. The yop genes are transcribed from strong promoters activated by a common transcription activator. Recombinant Y. enterocolitica strains expressing the B subunit of the cholera toxin were constructed from a yopH-ctxB operon fusion. Integration of the gene ctxB in the pYV plasmid itself, by a double crossing over, ensured its stability in the infecting bacteria. Oral inoculation of recombinant bacteria in mice elicited serum and intestinal antibody responses and resulted in protection of the immunized mice against a cholera toxin challenge. Secretory immunoglobulin A antibodies against the cholera toxin B subunit occurred not only in the intestines but also in the respiratory tract.

Administration, Oral↗
PubMed1992

Immunoglobulin A and interleukin 6 form a positive secretory feedback loop: a study of normal subjects and alcoholic cirrhotics.

Patients with alcoholic liver cirrhosis (ALC) have high serum levels and spontaneous in vitro production of immunoglobulin (Ig) A. Deposits of IgA are also found in liver sinusoids. Increased interleukin 6 (IL-6) production is another feature of this disease. This study shows a linear correlation between increased lipopolysaccharide (LPS)-induced IL-6 production and increased spontaneous IgA and IgG secretion by peripheral blood mononuclear cells (PBMCs). PBMCs and purified monocytes isolated from healthy control subjects and patients with ALC contain elevated IL-6 messenger RNA levels and produce IL-6 in response to stimulation with soluble polymeric IgA (p-IgA) or attached monomeric IgA (m-IgA) but not with soluble m-IgA. The addition of monospecific antibody to human IL-6 inhibits spontaneous IgA production by PBMC. This inhibition is more pronounced in patients with ALC. These data provide evidence that IgA, possibly by attachment to cells possessing Fc alpha receptors and secreting IL-6, is involved in the production of this major mediator and the amplification of Ig secretion. Circulating IgA and IgA deposits could therefore initiate a process of autoamplification implicated in the development of hypergammaglobulinemia in ALC.

Cells, Cultured↗
PubMed1992

Characterization of an anti-idiotypic MoAb bearing an internal image of the receptor-binding epitope of cholera toxin.

A mouse anti-cholera toxin (CT) MoAb, mAb1, specific for the GM1-binding epitope of CT, was used to raise a syngenic anti-idiotypic MoAb, mAb2. Purified mAb2 was specific for mAb1 as shown by latex particle counting immunoassay and ELISA. Several experiments of competition between mAb2 and CT for binding to mAb1 demonstrated that mAb2 bore an internal image of the GM1-binding epitope of CT. Binding of mAb2 to GM1 unambiguously corroborated the mAb1-paratopic specificity of mAb2. Furthermore, mAb2 acted as a CT-surrogate antigen: rabbits injected with mAb2 produced some anti-CT antibodies, Ab3, which resembled mAb1 in specificity as expected. The potential use of this mAb2 as vaccine or as prophylactic agent to prevent CT from binding to its cellular receptor is discussed.

Animals↗
PubMed1992

Effect of intrajejunal elemental diet perfusion on jejunal secretion of immunoglobulins, albumin, and hyaluronan in man.

The aim of this work was to study the jejunal secretion of immunoglobulins (Ig), albumin, and hyaluronan in response to jejunal perfusion of an elemental diet. A four lumen tube with a proximal occluding balloon at the angle of Treitz was used for jejunal perfusion in seven healthy volunteers (mean age 23 years). The length of the test segment was 40 cm. The jejunum was successively perfused with a control electrolyte solution for 80 minutes and with an elemental diet (containing 20.5 milligrams of free amino acids and 104.2 milligrams of oligosaccharides) for 100 minutes. The jejunal fluid concentrations of albumin, IgG, monomeric IgA (m-IgA), polymeric IgA (p-IgA), IgM, secretory component, and hyaluronan were measured and their jejunal outputs calculated. Within 20 minutes of starting perfusion with the elemental diet there was a significant increase in the secretion rates of albumin (x3.3), IgG (x5), M-IgA (x3.7), p-IgA (x2), IgM (x2), and secretory component (x1.6), but the hyaluronan secretion rate was not changed. The increase in m-IgA, p-IgA, IgM, and secretory component output suggests that intestinal perfusion of an elemental diet results in stimulation of secretory immunity. The increase in albumin and IgG output probably reflects a nutrient induced leakage from the plasma compartment.

Adult↗
PubMed1992

Transient developmental expression of IgY and secretory component like protein in the gut of the axolotl (Ambystoma mexicanum).

We previously reported that a primitive vertebrate, the Mexican axolotl (Amphibian, Urodela) synthesizes two classes of immunoglobulins. IgM are present in serum early in the development, and represent the bulk of specific antibody synthesis after an antigenic challenge. IgY occur in the serum later during the development, and are relatively insensitive to immunization. We demonstrate in the present work, using immunofluorescence with specific Mabs, that IgY are expressed in the gut epithelium, as secretory molecules. Secretory IgY are well expressed in the stomach and intestinal mucosae of young animals from 1 month after hatching to the seventh month. Thereafter, IgY progressively disappear from the gut and become readily detectable in the serum of 9-month-old preadult immunologically mature animals. Axolotl IgY are closely associated in the gut to secretory component-like (SC) molecules that are well-recognized by antisera to the SC of different mammalian species. This is the first description, in a primitive tetrapode, of an immunoglobulin class that could be the physiological counterpart of mammalian IgA.

Ambystoma mexicanum↗
PubMed1992

[IgA deficiency].

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Autoimmune Diseases↗
PubMed1991

The polymeric immunoglobulin receptor (secretory component) mediates transport of immune complexes across epithelial cells: a local defense function for IgA.

The polymeric immunoglobulin receptor (pIgR) on mucosal epithelial cells binds dimeric IgA (dIgA) on the basolateral surface and mediates transport of dIgA to the apical surface. Using Madin-Darby canine kidney epithelial cells stably transfected with pIgR cDNA, we found that soluble immune complexes (ICs) of 125I-labeled rat monoclonal antidinitrophenyl (DNP) dIgA (125I-dIgA) and DNP/biotin-bovine serum albumin were transported from the basolateral to the apical surface and then released. Monomeric IgA ICs were not transported, consistent with the specificity of pIgR for polymeric immunoglobulins. Essentially all the 125I-dIgA in apical culture supernatants was streptavidin precipitable, indicating that dIgA remained bound to antigen during transcytosis. While both dIgA and dIgA ICs bound pIgR with equal affinity (Kd approximately 8 nM), the number of high-affinity binding sites per cell was 2- to 3-fold greater for dIgA than for dIgA ICs. The extent of endocytosis of dIgA and dIgA ICs was correlated with the number of high-affinity binding sites. SDS/PAGE analysis of intracellular dIgA and dIgA ICs demonstrated that in both cases IgA remained undegraded during transport. The results suggest that the pathways of epithelial transcytosis of free dIgA and dIgA ICs are the same. Given the high population density of mucosal IgA plasma cells and the enormous surface area of pIgR-expressing mucosal epithelium, it is likely that significant local transcytosis of IgA ICs occurs in vivo. Such a process would allow direct elimination of IgA ICs at the mucosal sites where they are likely to form, thus providing an important defense function for IgA.

Animals↗