Resuscitation-induced gut edema and intestinal dysfunction.

BACKGROUND: Mesenteric venous hypertension and subsequent gut edema play a pivotal role in the development of intra-abdominal hypertension. Although gut edema is one cause of intra-abdominal hypertension, its impact on gut function is unknown. The purpose of this study was to create a model of acute hydrostatic gut edema and to evaluate its effect on gut motility and barrier function. METHODS: The first study, group A, evaluated the effect of gut edema on transit over time using 20 mL/kg 0.9% saline. The second study, group B, focused on the 12-hour time period using 80 mL/kg 0.9% saline. Rats were randomized to superior mesenteric vein partial occlusion (venous hypertension) or sham surgery. At 6, 12, and 24 hours, group A underwent intestinal transit and tissue water weight measurements. At 12 hours, group B underwent tissue water, transit, ileal permeability and resistance, lactate and myeloperoxidase activity, and mucosal injury measurements. RESULTS: Venous hypertension with fluid resuscitation caused acute hydrostatic gut edema, delayed intestinal transit, increased mucosal permeability to macromolecules, and decreased tissue resistance over time. Mucosal injury was minimal in mesenteric venous hypertension. CONCLUSION: Acute mesenteric venous hypertension and resuscitation-induced gut edema, in the absence of ischemia/reperfusion injury, is associated with delayed intestinal transit and altered gut barrier function.

Differential effects of prophylactic, concurrent and therapeutic lactoferrin treatment on LPS-induced inflammatory responses in mice.

Mice injected with endotoxin develop endotoxaemia and endotoxin-induced death, accompanied by the oxidative burst and overproduction of inflammatory mediators. Lactoferrin, an iron binding protein, provides a natural feedback mechanism to control the development of such metabolic imbalance and protects against deleterious effects of endotoxin. We investigated the effects of intraperitoneal administration of human lactoferrin on lipopolysaccharide (LPS)-induced release of tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), interleukin 10 (IL-10) and nitric oxide (NO) in vivo. Lactoferrin was administered as a prophylactic, concurrent or therapeutic event relative to endotoxic shock by intravenous injection of LPS. Inflammatory mediators were measured in serum at 2, 6 and 18 h post-shock induction. Administration of lactoferrin 1 h before LPS resulted in a rather uniform inhibition of all mediators; TNF by 82%, IL-6 by 43%, IL-10 by 47% at 2 h following LPS injection,and reduction in NO (80%) at 6 h post-shock. Prophylactic administration of lactoferrin at 18 h prior to LPS injection resulted in similar decreases in TNF-alpha (95%) and in NO (62%), but no statistical reduction in IL-6 or IL-10. Similarly, when lactoferrin was administered as a therapeutic post-induction of endotoxic shock, significant reductions were apparent in TNF-alpha and NO in serum, but no significant effect was seen on IL-6 and IL-10. These results suggest that the mechanism of action for lactoferrin contains a component for differential regulation of cellular immune responses during in vivo models of sepsis.

Down-regulation of inducible nitric-oxide synthase (NOS-2) during parasite-induced gut inflammation: a path to identify a selective NOS-2 inhibitor.

Nitric oxide (NO) possesses potent anti-inflammatory properties; however, an over-production of NO will promote inflammation and induce cell and tissue dysfunction. Thus, the ability to precisely regulate NO production could prove beneficial in controlling damage. In this study, advantage was taken of the well characterized inflammatory response caused by an intestinal parasite, Trichinella spiralis, to study the relationship between intestinal inflammation and the regulation of nitric oxide synthase-type 2 (NOS-2) expression. Our study revealed that a specific gut inflammatory reaction results in inhibition of NOS-2 expression. Characteristics of this inhibition are: 1) local jejunal inflammation induced by T. spiralis systemically inhibits NOS-2 gene transcription, protein expression, and enzyme activity; 2) the inhibition blunts endotoxin-stimulated NOS-2 expression; 3) the inhibition does not extend to the expression of other isoforms of NOS, to paxillin, a housekeeper protein, or to cyclooxygenase-2, another protein induced by proinflammatory cytokines; 4) the inhibition is unlikely related to the formation of specific anti-parasite antibodies; and 5) the inhibition may involve substances other than stress-induced corticosteroids. Elucidation of such potent endogenous NOS-2 down-regulatory mechanisms could lead to the development of new strategies for the therapy of inflammatory conditions characterized by the overproduction of NO.

Intestinal anaphylaxis in chickens: epithelial ion secretion as a determinant and potential component of functional immunity.

Immunity to secondary protozoan infections in chickens is accompanied by rapid onset of intestinal permeability to serum proteins, an event in mammals associated with local anaphylaxis. The permeability changes in the chicken intestine are hypothesized to be mediated by mast cell-derived paracrine factors. In a test of this hypothesis, we demonstrated, using an electrophysiological correlate of intestinal anaphylaxis (antigen-induced Cl(-) secretion), that the response of the chicken intestine to antigenic stimulation is consistent with type I hypersensitivity reactions. Day-old, single-comb-white-Leghorn chickens were sensitized to bovine serum albumin (BSA). At 3 weeks of age ileal segments were mounted in Ussing-type chambers. Serosal challenge with BSA elevated the transmural short circuit current (DeltaIsc) within 1min and was maximally expressed (DeltaIsc=50-60microA/cm(2)) within 2-3 min. The magnitude of the DeltaIsc was directly related to the concentration of antigen (10-200 microg antigen/ml), was only expressed in immunized chickens, and was blocked by the mucosal application of a Cl(-) channel blocker. Data obtained in the present investigation identify epithelial ion secretion as a potential mechanism of functional immunity in the mucosal immune system of the chicken small intestine.

Ileal mucosal response to bacterial toxin challenge.

BACKGROUND: The cause of postinjury intestinal mucosal barrier disruption remains obscure. The present study examines the hypothesis that the bacterial toxin formyl-methionyl leucyl phenylalanine (FMLP) plays an initial role in this process. METHODS: Mucosal permeability to fluorescein isothiocyanate-labeled dextran (4,400 molecular weight) was measured in perfused distal rat ileum with and without FMLP. Dextran and myeloperoxidase appearance in the lumenal perfusate was assessed in response to surrogates of traumatic stress: ischemia/reperfusion, total abdominal irradiation, and total parenteral nutrition. Recovery of FMLP in the effluent of static closed and perfused ileal loops was determined by mass spectrometry. Release of mast cell mediators in the presence of FMLP was determined in ileal everted sacs. RESULTS: Seventy-five percent of FMLP was recovered in perfusion effluent in contrast to 5% in closed loops. There was a transient increase in ileal permeability in FMLP/perfused, untreated rats, and in ischemia/reperfusion and total parenteral nutrition treated rats that was recorded with a concomitant increment in myeloperoxidase (inflammatory marker) in all experimental models except irradiated rats, which were unresponsive to FMLP. FMLP responsiveness was associ. ated with a significant rise in release of serotonin (mast cell mediator). CONCLUSION: These results suggest that mast cells and other resident inflammatory cells within the gut wall are involved in FMLP-induced changes in mucosal barrier permeability and raise the possibility that under conditions of traumatic stress, proinflammatory mediators within the gut wall might be activated by toxic factors in the gut lumen.

Lactoferrin protects gut mucosal integrity during endotoxemia induced by lipopolysaccharide in mice.

The hypothesis that lactoferrin protects mice against lethal effects of bacterial lipopolysaccharide (LPS) is the subject of experimental investigations described in this article. Lipopolysaccharide is a powerful toxin produced by gram negative bacteria that when injected into humans or experimental animals reproduce many of the pathophysiologic and immune responses caused by live bacteria. Lactoferrin administered intraperitoneally 1 hr prior to injection of LPS significantly enhanced the survival of mice, reducing LPS-induced mortality from 83.3% to 16.7%. Changes in locomotor and other behavioral activities resulting from LPS injection were not present in mice treated with lactoferrin. Also, histological examination of intestine revealed remarkable resistance to injury produced by LPS if mice were pretreated with lactoferrin. Severe villus atrophy, edema and epithelial vacuolation were observed in LPS-treated animals but not in lactoferrin-treated counterparts. Electrophysiological parameters were used to assess secretory and absorptive functions in the small intestine. In mice treated with LPS, transmural electrical resistance was reduced and absorption of glucose was increased. Lactoferrin treatment had no significant influence on basal electrophysiological correlates of net ion secretion or glucose absorption nor on changes induced by LPS. Collectively, these results suggest that lactoferrin attenuates the lethal effect of LPS and modulates behavioral and histopathological sequela of endotoxemia.

Fish oil supplementation does not impair the gut immune response to Trichinella spiralis infection in rats.

BACKGROUND: Fish oil has been recommended as a source of omega-3 fatty acids for preterm infants and for therapy of some inflammatory diseases. METHODS: Because fish oil supplementation could downregulate the host's immune response, we studied the gut inflammatory response to an enteric infection in 72 rats assigned to three dietary groups with differing fatty acid profile: 1) fish oil, rich in eicosapentaenoic and docosahexaenoic acid; 2) olive oil, containing 71% monounsaturated fat; and 3) rat chow, containing 57% saturated fat. One half (n = 36) of the rats were infected with Trichinella spiralis larvae; the other half served as controls. The inflammatory response to initial infection (study 1), and type I hypersensitivity response to a subsequent parasite-derived antigenic challenge (study 2) were assessed. Jejunal inflammatory cell infiltrate, mean villus height, disaccharidase levels, changes in short-circuit current in response to glucose absorption, and chloride secretagogues (study 1) were measured 9 days after infection. Short-circuit current changes induced by chloride secretion were measured when the proximal jejunum was challenged with T. spiralis-derived antigen 40 days after infection (study 2). RESULTS: In study 1, jejunal tissue from infected animals had more eosinophilic infiltrate, lower disaccharidase levels, and less glucose absorptive and chloride secretory capacity than tissue from noninfected animals. In study 2, the jejunum of infected animals showed an antigen-induced chloride secretory response, whereas no response was obtained from jejunal tissue from noninfected animals. Type of diet did not affect the response in either study. CONCLUSION: Under the conditions of this experiment, fish oil supplementation did not interfere with the local intestinal inflammatory response after T. spiralis infection.

The gut. A key metabolic organ protected by lactoferrin during experimental systemic inflammation in mice.

The gastrointestinal tract may be viewed as an ecologic system in which a balance between the host and bacterial flora exists. Two major host components appear to be involved in maintaining this balance. The first is a non-specific structural barrier provided by the epithelial layer of the gastrointestinal mucosae. The second component involves functional immunological elements found in the mucosal and submucosal compartments, e.g., gut associated lymphoid tissue. When gut integrity is disrupted by invasive pathogens or by trauma, a myriad of pro-inflammatory mediators are released from cells in the gut wall that exert actions in the tissue or gut lumen. One of these mediators is lactoferrin, and iron binding protein found in high concentration in most human exocrine secretions. Despite controversies on its physiological role, evidence is emerging that lactoferrin plays an important role in host defense against toxic metabolites and antigenic components of potential pathogens2-4. This manuscript is intended to provide an overview of work related to lactoferrin's modulatory roles in inflammation, and to present observations from experimental studies on the preservation of intestinal structure and function by lactoferrin during intestinal inflammation. The possibility that lactoferrin limits the autodestructive inflammatory responses presents a new alternative for the future management of systemic inflammation.

Nutritional support for adaptation to radiation-induced suppression of mucosal immunity in the intestine of the rat.

Appropriate enteral nutrition provided immediately after injury or trauma to the gastrointestinal tract may limit or reverse damage to the mucosal barrier. In this regard, diets containing amino acids, such as arginine and glutamine, or fish oil have been identified as beneficial. This report assesses the role of amino acids as "essential nutrients" in the repair of intestinal mucosa damaged by gamma radiation. Rats were used experimentally to test the hypothesis that the recovery of the immune responses in the intestinal mucosa, which are suppressed by radiation, can be improved by feeding an elemental amino acid diet, referred to hereafter as the diet, immediately after irradiation. The objective was to assess the impact of the diet on the expression of type I hypersensitivity or anaphylaxis in the jejunal mucosa. The local expression of this immunological response, which involves several radiosensitive cell types, was studied in rats immunized by oral infection with the nematode parasite, Trichinella spiralis. Rats that recover from infection become immunized and their small intestine undergoes anaphylaxis when subsequently challenged with parasite-derived antigen. This hypersensitivity response is expressed, in part, as Cl- secretion and can be observed in vitro or in vivo. When challenge is provided by a secondary inoculum of infective T. spiralis larvae, Cl- secretion is accompanied by fluid secretion and by the rapid expulsion of the parasite from the intestine. Immunized rats maintained on a stock diet and exposed to 7 Gy of total-abdominal irradiation from a cobalt-60 gamma-ray source failed to express antigen-induced Cl- secretion fully for up to 14 days postirradiation, and rejection of the parasite was suppressed for at least 30 days postirradiation. The suppression of immune responsiveness is associated with the disappearance of intestinal mucosal mast cells, which normally trigger the anaphylactic response. When rats are maintained on the diet after irradiation, the capacity to reject the parasite remains suppressed. However, the ability to express anaphylaxis-mediated Cl- secretion returns by 3 days postirradiation. The quick, diet-supported recovery of antigen-induced Cl- secretion occurs despite the continued absence of mast cells. Although the recovery of anaphylaxis-mediated responses suppressed by irradiation is only partial, our experimental results underscore the potential for enhancing the recovery process through nutritional support.

Relative allergenicity of cow's milk and cow's milk-based formulas in an animal model.

Human infants fed cow's milk or cow's milk-based formula may become intolerant to milk proteins partially because of allergic reactions. However, the relative allergenicity of these diets has not been clearly determined at the intestinal level. In this study, the allergenicity of cow's milk and milk-based formula was evaluated by examining intestinal anaphylaxis caused by challenge with a milk protein fraction, beta-lactoglobulin (beta LG), in guinea pigs orally sensitized to these diets. Colonic segments were removed and challenged with beta LG. An antigen-induced, anaphylactically mediated elevation of transmural short circuit current, which is caused by net chloride (Cl-) secretion, was measured in Ussing chambers as an index of local immune responsiveness. After removal of the colon, all guinea pigs were challenged by intracardiac injection with beta LG to examine the onset of bronchospasm, a test for systemic anaphylaxis. Whereas colonic segments from all guinea pigs fed whole cow's milk responded to challenge with beta LG, segments from only 60% of animals fed cow's milk formula responded to the challenge. In addition, the responders in the latter group had a significantly lower magnitude of beta LG-induced Cl- secretion compared with animals sensitized to whole cow's milk. In parallel, bronchospasm developed in all guinea pigs fed whole cow's milk. In the group of animals fed cow's milk formula, bronchospasm developed only in those who responded to the intestinal challenge. On the basis of these results, cow's milk-based formula has less sensitizing power than whole cow's milk in our animal model, and our approach is effective in testing allergenicity at the intestinal level.

Progesterone modulation of anaphylactically induced ion transport in uterus and intestine.

The objective of this study was to investigate the role of progesterone in modulating electrophysiological responses to antigenic challenge that are reflective of immune functions in uterine and jejunal mucosae. In the rat-Trichinella spiralis, host-parasite system, an enteric infection with a microscopic nematode sensitizes both the jejunum and uterus. Electrophysiological correlates of local anaphylaxis or type I hypersensitivity were monitored in vitro throughout the estrus cycle and during pregnancy. The magnitude of the anaphylactic response was correlated with serum levels of progesterone. Functional immunity was measured directly in the intestine by assessing the development of acquired resistance to reinfection with T. spiralis. Results support the conclusion that high progesterone output, as occurs during metestrus and pregnancy, and exogenously administered hormone suppress uterine responsiveness. However, the reduced uterine sensitivity to challenge could be attributed to nonspecific physiological effects of progesterone rather than direct effects on immunological components involved in the transduction of the antigenic signal. The electrophysiological response to antigen in the intestine was relatively refractory to effects of progesterone. These observations add to our understanding of endocrine control of mucosal responses to antigenic challenge and underscore site selectively of hormonal action.

Intestinal anaphylaxis: radiation-induced suppression.

The gastrointestinal tract is highly sensitive to ionizing radiation. Some of the most radiosensitive cells in this system are mast cells and epithelium. This article describes experiments that test the hypothesis that irradiation suppresses mucosal immune responses in which mast cells and epithelium are involved. The hypothesis was tested by examining the impact of ionizing radiation on anaphylactically mediated Cl- secretion in jejunum of rats sensitized by Trichinella spiralis infection and challenged with antigen derived from the parasite. Antigen-induced Cl- secretion was measured electrophysiologically in vitro. Rats were immunized by inoculation with 3 x 10(3) T. spiralis larvae and, 30-50 days later, exposed to total abdominal irradiation from a cobalt-60 gamma source. Doses were 5, 7, and 9 Gy. At 1, 3, 5, 7, 14, and 21 days postirradiation (DPI), jejunal segments were assessed for immune responsiveness. (Duration of suppression to antigenic challenge was directly related to radiation dose). Recovery of response to antigenic challenge after irradiation with 5 Gy was complete by 5 DPI. At 7 Gy, responsiveness was totally suppressed from 1 to 5 DPI, was partially expressed from 5 to 14 DPI, and was completely restored by 21 DPI. A dose of 9 Gy completely suppressed immune responsiveness throughout the 21-day period. Full responsiveness of jejunum to exogenous Cl- secretagogues at 1-5 DPI indicates that the immunosuppressive effect of radiation was not due to a breakdown in the secretory process at the epithelium level.(ABSTRACT TRUNCATED AT 250 WORDS)

Structural and molecular changes in intestinal smooth muscle induced by Trichinella spiralis infection.

Infection with Trichinella spiralis in the rat causes altered intestinal motility and jejunal smooth muscle contractility by day 6 postinoculation. The purpose of this study was to determine structural and molecular changes in the smooth muscle that could account for the functional changes that have been reported. By day 6 postinoculation, there was an increase in thickness of both muscle layers of the jejunum. This increase in mass was accompanied by an increase in total protein content of the seromuscular tissues. When specific proteins were analyzed, increases in actin and myosin heavy chain contents were found. On the other hand, there was no increase in collagen content. Alterations in gene expression at the pretranslational level were determined by monitoring total RNA and the proportion of mRNA that codes for alpha-smooth muscle actin. There was an increase in both parameters in longitudinal muscle from the jejunum of infected animals. The increase appeared to be site selective because there were no increases in either parameter in longitudinal muscle of the distal intestine. These results indicate that pretranslational upregulation of gene expression for actin isoforms occurs in smooth muscle of the proximal but not distal intestine during the early enteric phase of infection with T. spiralis. Thus the altered smooth muscle contractility that has been reported in experimental trichinosis may be related in part to an increased expression of smooth muscle protein.

Use of a modified Ussing chamber to monitor intestinal epithelial and smooth muscle functions.

A technique that allows the simultaneous monitoring of epithelial and smooth muscle function was developed and used to study rat small intestine in vitro. A Ussing chamber was modified so that a strain gauge force transducer could be sewn to the serosal surface of an intestinal segment clamped in the chamber. The apparatus was used to monitor short-circuit current, potential difference, and resistance across the segment, and contractions of the longitudinal layer of the muscularis externa. Both spontaneous activity and responses to the application of carbachol were recorded. Carbachol applied to the serosal side induced dose-dependent increases in both short-circuit current and contractile force. The median effective doses of the two responses differed, with contractions being more sensitive to the drug. Carbachol applied to the mucosal side induced no changes in either epithelial or contractile activities. The ability of the serosal strain gauge transducer to monitor contractions faithfully was tested in an organ bath in which the gut segment was attached to an external force-displacement transducer. There was a close correlation between the dose-dependent increase in force in response to carbachol measured by the serosal transducer and that measured by the force-displacement transducer (r = 0.988). Thus our technique can be used to study simultaneously epithelial and smooth muscle functions of the intestine.

Reconstruction of immune-mediated ion secretion in gut mucosa of the athymic rat.

A defect in an immune-mediated, physiological reaction in the small intestine of congenitally immunosuppressed rats has been identified and corrected by recoupling the immunological trigger in the mucosa with epithelial effector cells. Antigenic challenge of jejunum from euthymic rats sensitized by infection with Trichinella spiralis evoked an anaphylactic response in vitro that was characterized by an elevation in transmural short-circuit current (Isc) and caused by net Cl- secretion. In contrast, jejunum from previously infected athymic counterparts failed to respond electrophysiologically to antigenic stimulation. Passive immunization of athymic rats with anti-Trichinella serum restored jejunal responsiveness to antigen. Jejunal unresponsiveness to antigenic challenge in the athymic rat compared with the euthymic rat was not due to a difference in the duration of exposure to the sensitizing antigens, mast cell numbers, inflammation-related histological changes nor to reduced responsiveness of epithelium to Cl- secretagogues. Because the transduction of the antigenic signal into epithelial ion transport changes in euthymic rats requires IgE, mucosal mast cells, mast cell-derived mediators and enteric nerves, the results support the conclusion that an antibody deficiency is the only functional defect preventing the antigen-induced change in mucosal ion transport in the athymic host.

Immunoregulation of endometrial and jejunal epithelia sensitized by infection.

The hypothesis was tested that the uterus of the rat orally infected with the parasite Trichinella spiralis becomes hypersensitized and that subsequent antigenic challenge affects functions in the endometrial epithelium. Results of experiments comparing the immunological responsiveness of isolated rat uterus with that of the jejunum supports our hypothesis. Antigenic challenge of uterus mounted in Ussing-type chambers causes an elevation in transuterine short circuit current (Isc) of 6.4 +/- 0.8 microA/cm2. The transduction of the antigenic signal to elicit the electrophysiological response involves 5-hydroxytryptamine (5-HT) working through a nerve-independent pathway. The antigen-stimulated rise in Isc peaks approximately 3 min after challenge. The uterine response is blocked by diisothiocyanostilbene-2,2'-disulfonic acid, an inhibitor of bicarbonate-chloride exchange. The antigen-evoked change in jejunal Isc is biphasic, peaking at 1.5 and approximately 4.0 min after challenge, and is about 10-fold greater in magnitude than the Isc in the uterus. The transductive pathway in the jejunum involves 5-HT, histamine and prostaglandin acting partly through intrinsic nerves. The jejunal response to antigen is inhibited by diphenylamine-2-carboxylate, a chloride channel blocker. Changes in net ion transport which are primed by infection and evoked by antigen are apparently triggered by local anaphylaxis in both the uterus and jejunum.

Immunological sensitization of opossum gallbladder by naturally acquired stomach roundworm infection.

1. The opossum gallbladder develops an immediate type hypersensitivity as a result of chronic infection with the gastric nematode, Physaloptera turgida. 2. Hypersensitization is evident from a change in net transepithelial ion transport in response to parasite-derived antigen. 3. The antigen-induced change in ion transport involves mediation by histamine and possibly prostaglandins and is independent of intrinsic neural modulation. 4. The functions of the gallbladder epithelium are influenced by reactions of local immune elements that are part of the common mucosal immune system.

Biliary and gut function following shock.

The aim of this study was to characterize the alterations in gallbladder and intestinal function after hemorrhagic shock and blood reperfusion in opossums. Animals were subjected to a shock of 30 mm Hg of arterial blood pressure for 60 minutes and resuscitated with blood reinfusion. Gallbladder epithelial ion transport, gallbladder motility in vitro and in vivo, gastrointestinal motility, and flora of the stomach and small bowel were studied 2 and 24 hours after shock. Changes at 2 hours included decreased gallbladder contractility in vitro and decreased emptying in vivo, loss of coordination with intestinal motor activity, decrease in frequency of intestinal electrical slow waves, and reduced duration of the intestinal migrating motor complex cycle. By 24 hours, gallbladder epithelial permeability was increased and in vitro contractility remained reduced but the in vivo functions showed partial recovery. Gastrointestinal flora was not affected by these changes. These data demonstrate that hemorrhagic shock and reperfusion affect digestive motility. The early timing of the alterations observed and the partial recovery 24 hours post shock suggest an ischemia-hypoxia mechanism of injury.

Simulation of parasite-induced gut hypersensitivity: implications for vaccination.

Antigenic challenge of jejunum from rats infected with Trichinella spiralis evokes a biphasic pattern of epithelial Cl- secretion, as measured in vitro by electrophysiological methods. Peaks of secretion occur at approximately 1.5 and approximately 5.0 min post-challenge. Challenge of jejunum from hosts passively immunized with serum containing anti-Trichinella anaphylactic antibody evokes the late phase but not the early phase of Cl- secretion. Since the early phase is mediated by 5-hydroxytryptamine and histamine from mast cells, we hypothesized that the failure to express that phase was due to a decrease in mast cell-derived mediators secondary to a deficiency in mucosal mast cell numbers. The hypothesis was tested by correlating mast cell numbers with patterns of antigen-induced Cl- secretion using several immunization regimes. Rats actively immunized by infection produced anti-Trichinella IgE and had a mucosal mastocytosis. Rats passively sensitized with serum containing anti-Trichinella IgE had normal numbers of mast cells in their mucosa. Inducing mastocytosis in rats, by infecting them with Nippostrongylus brasiliensis prior to passive sensitization with anti-Trichinella serum, primed for the expression of a biphasic Cl- secretory response upon subsequent challenge with Trichinella antigen. Rats actively sensitized by injection with Trichinella antigen elicited an IgE response without mastocytosis and expressed only the late phase of antigen-induced Cl- secretion. Results (i) support our hypothesis, (ii) emphasize the importance of the cellular state of the mucosa in the functional expression of local anaphylaxis; and (iii) provide a physiological explanation for the general failure of vaccination and passive sensitization to induce functional immunity equivalent to that induced by natural infection.

Evaluation of a possible functional relationship between chemical structure of intestinal brush border and immunity to Trichinella spiralis in the rat.

Primary exposure to Trichinella spiralis in the rat, while immunizing against reinfection, induces changes in the carbohydrate structure of intestinal brush border membranes. Immunity is expressed in heightened resistance to mucosal invasion by L1 larvae, and the change in structure is evident in reduced membrane binding of the lectin, wheat germ agglutinin. The possibility that altered membrane composition is a requisite for expression of immunity was hypothesized and this was evaluated by correlating the maximum, specific binding of wheat germ agglutinin by isolated brush border membranes with (1) the expression of immunity acquired passively through serum transfer, and (2) the loss of immunity acquired from serial infections terminated in the intestinal phase. The hypothesis was further evaluated by determining whether the change in membrane structure represents a stimulus-specific response. We observed that (1) passively acquired immunity was not associated with a reduction in lectin binding and (2) short-term exposure to the intestinal stages of T. spiralis led to a reduction in lectin binding that was detectable at a time when rats were incapable of resisting reinfection. The change in lectin binding associated with trichinosis also accompanied infection with Nippostrongylus brasiliensis. Results uniformly support the conclusion that immunity to T. spiralis is independent of brush border membrane changes reflected in reduced binding of wheat germ agglutinin.