Intestinal uptake of carrageenan: distribution and effects on humoral immune competence.
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Administration, Oral↗
Biomedical subjects
S Nicklin
Publications and source records attributed to S Nicklin.
Carrageenan induced changes in the immunomodulatory capacity of macrophages: an in vitro study.
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Animals↗
Naturally acquired tolerance to dietary antigen: effect of in utero and perinatal exposure on subsequent humoral immune competence in the rat.
Inbred PVG strain rats were used to investigate the effects of dietary exposure to ovalbumin during the early stages of development on the subsequent induction of ovalbumin-specific antibody responses. An ovalbumin-containing diet was administered to rats during pregnancy and/or for scheduled periods during lactation. All offspring were weaned onto a conventional diet and subsequently challenged parenterally and/or orally with ovalbumin. The effects of the various feeding regimens on the subsequent reaginic, biliary and serum anti-ovalbumin antibody response were examined. Animals exposed to ovalbumin during gestation and/or the post-partum period presented increased levels of biliary anti-ovalbumin antibody activity yet remained systemically tolerant to this antigen following parenteral challenge. These findings are discussed in relation to possible mechanisms responsible for promoting naturally acquired tolerance to dietary antigens.
Animals↗
Suppression of thymocyte proliferation in vitro by a dioctyltin dichloride-induced serum factor.
Oral administration of dioctyltin dichloride (DOTC) results in the production or release of factors which appear to prevent thymocyte maturation at an early stage. Sera obtained from rats gavaged with 75 mg DOTC/kg on alternate days, significantly inhibited PHA-induced blastogenesis of normal thymocytes. In vitro uptake of tritiated thymidine by thymocytes obtained from DOTC-gavaged rats was markedly reduced. These events occurred 24 to 72 h after commencement of DOTC treatment and preceded overt thymic weight loss. The effects of DOTC may therefore be a consequence of factor(s) capable of blocking the intrathymic differentiation of T cell precursors.
Animals↗
The role of carrageenan in complement activation.
A study has been made of the nature of the interaction between complement and carrageenan, which has been widely reported to inhibit haemolytic complement activity both in vivo and in vitro. Using modified haemolytic complement-fixation tests, the degree of complement consumption by various forms of carrageenan was measured in whole human and rat sera. The median effective concentrations of the carrageenans studied were found to lie in the range 3-300 micrograms/ml for the classical pathway and 500-7800 micrograms/ml for the alternative pathway and were unrelated to sulphate content, as determined by energy dispersive X-ray analysis. It was also found that carrageenan-coated sheep erythrocytes were lysed by complement. This activity was suppressed by ethylene glycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, which inhibits the classical, but not the alternative pathway, providing conclusive evidence that carrageenan preferentially activates the classical pathway. This finding may help in elucidating the inflammatory reaction induced by carrageenan.
Animals↗
Extravasation assay for the assessment of intestinal reactions to orally presented compounds.
Adverse reactions characteristic of food intolerance are claimed to occur in susceptible individuals following exposure to various chemical additives used to colour, flavour or preserve food. The objective of the present study was to develop a method suitable for investigating the nature and mechanism of these reactions in an animal model. Our results demonstrate that intestinal responses, elicited either specifically following oral challenge by antigen or non-specifically by the direct action of a chemical, can be quantified by evaluating the intestinal extravasation (IEV) of intravenously administered 125I-labelled rat albumin.
Animals↗
Effect of orally administered dioctyltin dichloride on murine immunocompetence.
The immunotoxicological effects of di(n-octyl)tin dichloride (DOTC) in the mouse were measured using a well-defined system to monitor alterations in immune responsiveness towards both self and heterologous cell membrane components. Oral weekly administration of DOTC caused a suppression of the anti-self erythrocyte antibody response. The humoral response against rat erythrocytes was also diminished. Although humoral responsiveness was affected only at a dose level which caused thymic atrophy (500 mg/kg body wt) the delayed type hypersensitivity reaction to oxazolone, a measure of cell-mediated immunity, was not affected. These data indicate that DOTC can suppress specific aspects of murine immunocompetence and may be relevant in designing studies for assessing possible hazards associated with environmental chemicals.
Administration, Oral↗
The effect of dioctyltin dichloride on the thymus and T-cell differentiation in the rat.
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Animals↗
Influence of dietary carrageenans on microbial biotransformation activities in the cecum of rodents and on gastrointestinal immune status in the rat.
Rats, mice, and hamsters were fed iota-carrageenan incorporated in a fiber-free, purified diet for 30 days, and the activities of a number of cecal microbial enzymes were determined in vitro. Carrageenan treatment produced cecal enlargement in all species, yet significantly decreased the concentration of bacteria per gram of cecal content. Azoreductase, beta-glucosidase, beta-glucuronidase, nitrate reductase, and nitroreductase activities per gram of cecal content were significantly decreased in the rat, although less consistent effects were found in these enzymes in the mouse and hamster. beta-Glucuronidase and nitrate reductase functions were increased per gram of cecal contents in the hamster. The total activity per cecum of certain of these enzymes was modified by the concomitant cecal enlargement, yet total nitroreductase activity was significantly decreased in all three rodent species. iota-Carrageenan significantly decreased the concentration of enterobacteria, staphylococci, streptococci, lactobacilli, facultative anaerobes, and the total microscopic count in the rat cecum, but did not exert any effect on bacterial viability in vitro. Although having no effect on biliary IgA antibody concentration, iota- and kappa- carrageenan when present at 50 g/kg diet increased the agglutination response of the IgA specific for the hindgut microflora.
Administration, Oral↗
Iota-carrageenan induced reaginic antibody production in the rat--I. Characterisation and kinetics of the response.
The intraperitoneal injection of graded amounts of ovalbumin into inbred PVG strain rats was found to produce a dose dependent anti-ovalbumin antibody response without eliciting the production of ovalbumin-specific reaginic antibodies. The injection of ovalbumin admixed with iota-carrageenan enhanced the anti-ovalbumin response and simultaneously elicited the de novo production of reaginic anti-ovalbumin antibodies. Isotype analysis of the anti-sera revealed the presence of both IgG and IgE class anti-ovalbumin antibodies and demonstrated that non-reaginic IgE anti-ovalbumin antibodies were also a feature of this reaction. The reaginic antibody phase of the response, although transient in nature, was re-elicited by secondary antigen challenge. The administration of ovalbumin prior to the ovalbumin-carrageenan preparation was shown to abrogate the reaginic antibody response without significantly influencing the non-reaginic component of the response. Conversely the injection of iota-carrageenan prior to antigen, significantly suppressed the normal agglutinating anti-ovalbumin response but did not prevent the induction of reaginic antibodies. These observations demonstrate that iota-carrageenan can, under specific conditions, function as an efficient adjuvant, and is capable of by-passing the normal mechanisms responsible for controlling antigen specific reaginic antibody production.
Animals↗
Induction of a transient reaginic antibody to tartrazine in an animal model.
The capacity of tartrazine to initiate reaginic antibody production was investigated in inbred rats. Parenteral administration of tartrazine, when covalently linked to a protein carrier and presented in association with carrageenan, resulted in the production of a transient tartrazine-specific reaginic antibody. This response could be enhanced by a secondary challenge, but declined rapidly and thereafter could not be re-elicited.
Adjuvants, Immunologic↗
Effect of orally administered food-grade carrageenans on antibody-mediated and cell-mediated immunity in the inbred rat.
Experiments were performed to investigate the immunological consequences associated with the persorption of poorly degradable carregeenans from the diet. Using an inbred strain of rat it was demonstrated histochemically, by the carrageenan-specific Alcian blue staining technique, that small quantities of food-grade carrageenans given at 0.5% in drinking-water for 90 days could penetrate the intestinal barrier of adult animals. This apparently occurred via an intact mucosa in the absence of inflammatory or pathological lesions. The carrageenan was demonstrated in macrophage-like cells present within the villi and lamina propria of the small intestine. The oral administration of kappa, lambda or iota food-grade carrageenans did not affect local (biliary) or systemic antibody responses to gut commensal microorganisms, or to orally-administered sheep erythrocytes. However, when sheep red blood cells were administered parenterally the ensuing anti-sheep red blood cell haemagglutinating antibody response was temporarily suppressed in carrageenan-fed rats. lambda-Carrageenan and iota-carrageenan both significantly (P less than or equal to 0.01 and P less than or equal to 0.05, respectively) reduced the mid-phase (14-28 days) haemagglutinin response; kappa-carrageenan (L100) was less effective but caused significant depression at day 21 (P less than or equal to 0.01). Individual responses were, however, within the control range 35 days after sheep erythrocyte administration, thus indicating the temporary nature of this effect. Although carrageenan administration depressed the anti-sheep erythrocyte antibody response, it did not affect T-cell immune competence as measured by the popliteal lymph node assay for graft-versus-host reactivity.
Administration, Oral↗
Prophylactic immunization against experimental leishmaniasis. II. Further characterization of the protective immunity against fatal Leishmania tropica infection induced by irradiated promastigotes.
The genetic vulnerability of BALB/c mice to Leishmania tropica (L. major) infection renders them incapable of controlling a primary cutaneous lesion that leads to uniformly fatal visceral disease. Potent, long-lasting protection involving both lesion healing and survival can be induced by repeated prophylactic i.v. immunization with gamma-irradiated (150K rad) L. tropica promastigotes. The effect is not dependent on continuing viability or cellular invasiveness of the irradiated parasites because their effective immunogenicity withstands heating at 56 degrees C for 1 hr. Immunity is not stage specific and encompasses both amastigote and promastigote challenges. Similar prophylaxis can be induced by immunization with heterologous irradiated L. donovani promastigotes. Repeated i.v. immunization with irradiated L. tropica promastigotes induces an antibody response in the isotype sequence M leads to G1/G3 leads to G2a/G2b leads to A with substantially higher titres than are found in response to the infection itself. Splenectomy before immunization drastically reduces this antibody response without incurring any impairment of the extent of protection. Passive transfer of large amounts (up to 10 ml) of hyperimmune serum (or isotype fractions thereof) throughout the first 8 wk of infection fails to arrest disease progression during this period. Despite the previously described lack of any detectable cutaneous DTH reactivity, which has hitherto correlated with protective cell-mediated immunity, the results obtained do not support attribution of an alternative causal role to the humoral response.
Animals↗
Local and systemic immune responses to intestinally presented antigen.
We have investigated the ability of the gut-associated lymphoid tissues (GALT) to react against standard antigens presented via different routes of administration. When antigens were presented directly to GALT, either by an injection into the Peyer's patches or via a mechanically damaged lamina propria, a rapid and vigorous immune response ensued. This was manifested systemically as an antigen-specific humoral antibody response in the serum and locally as an antigen-specific immunoglobulin A response in the bile. These results indicate that GALT is capable of reacting to foreign materials penetrating the gut wall. Additional experiments demonstrated that the extended feeding of degraded iota carrageenan, a material known to produce non-specific mucosal inflammation, caused GALT to react to antigenic molecules present within the gastro-intestinal tract and enhanced both serum and biliary antibody responses against specific gut commensal microorganisms. The immunological significance of these observations is discussed.
Administration, Oral↗
Abrogation of suppressor cell function by inhibitors of prostaglandin synthesis.
The weekly intraperitoneal injection of rat erythrocytes into mice induces both a stable autoimmune state, as judged by the appearance of anti-mouse erythrocyte autoantibody and suppressor T cells capable of regulating this response; the latter being demonstrable only in a subsequent transfer system. This autoimmune response and the parallel anti-rat erythrocyte response were both insensitive to exogenous prostaglandin E2 (PGE2). The administration of prostaglandin synthetase inhibitors (indomethacin or aspirin) to mice undergoing immunization with rat erythrocytes had no effect on the anti-rat response, yet mildly exacerbated the onset of the autoimmune state and potently inhibited the generation of suppressor cells. Furthermore the administration of these drugs to recipients of suppressor cells virtually abrogated suppressor cell activity. These observations imply that both the generation and effector function of these suppressor cells may be modulated by prostaglandin synthetase inhibitors while at the same time T helper and B cell functions remain unimpaired.
Anemia, Hemolytic, Autoimmune↗
Prophylactic immunization against experimental leishmaniasis: I. Protection induced in mice genetically vulnerable to fatal Leishmania tropica infection.
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Animals↗
Impairment of graft versus host reactivity in pregnant mice.
The popliteal lymph node (PLN) assay for graft versus host (GVH) reactivity has been used to analyse specific features associated with the immunological aspects of the materno-fetal relationship. GVH responses induced following the injection of maternal lymphocytes into F1 hybrid recipients is a particularly relevant model for testing the cellular reactivity of maternal lymphocytes against F1 hybrid determinants since every allogeneic pregnancy could initiate a naturally occurring mother versus F1 allograft reaction. Experiments monitored sequentially the effects of the pregnancy environment and multiparity on maternal cell-mediated immunity. The PLN assay performed within the confines of pregnant F1 hosts indicated that GVH reactivity was significantly suppressed during the mid and late stages of gestation with suppression being greatest in allogeneic combinations. In addition cells obtained from pregnant donors were less efficient than normal cells at GVH induction when transferred to virgin F1 recipients. The suppressive effect was maximal at mid-gestation; however, in this situation, the genotype of the paternal strain had no significant effect on the degree of immunosuppression observed. Multiparity in allogeneic combinations induced anti-paternal humoral immunity but an equivalent increase in GVH reactivity was not detected. These results support the concept of pregnancy-associated suppression of cell-mediated immunity. The nature of the suppressive effect is discussed.
Animals↗
[3H]Uridine uptake by target monolayers as a terminal label in an in vitro cell-mediated cytotoxicity assay.
A terminal labelling method is described for measuring cell-mediated cytotoxicity based on the ability of surviving target cells to incorporate [3H]uridine into their RNA precursor pools. Parameters of the system were examined using whole and damaged embryonic mouse fibroblast monolayers. This assay is less laborious than direct cell counting and gives increased sensitivity at low target to effector cell ratios. The labelling time is short and, unlike similar techniques, it allows target cell monolayers to remain intact after completion of the radioassay and available for histological examination. This is important where heterogeneous target populations are employed since it allows assessment of differential cell killing and eliminates the need for duplicate cultures. The assay was used in conjunction with a well defined mouse popliteal lymph node assay to investigate the appearance of cytotoxic cells during a localised graft versus host response. Results showed a direct correlation between proliferative index and the development of highly specific cell-mediated cytotoxicity.
Animals↗