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Role of mast cells in intestinal mucosal function: studies in models of hypersensitivity and stress.

A single layer of epithelial cells lines the gastrointestinal tract, forming a critical barrier between the lunminal contents, which includes antigens and other noxious substances, and the body proper. It has become clear in recent years that the role of mast cells in the gastrointestinal mucosa is not only to react to antigens, but also to actively regulate the barrier and transport properties of the intestinal epithelium. Mucosal mast cells respond to both IgE/antigen-dependent and non-IgE-dependent stimulation, releasing bioactive mediators into adjacent tissues where they induce physiological responses. Studies in models of hypersensitivity and stress have provided evidence that changes in mucosal function are due to either direct action of mast cell mediators on epithelial receptors and/or indirect action via nerves/neurotransmitters.

Animals↗

Accelerated rejection of Nematospiroides dubius intestinal worms in mice sensitized with adult worms.

After oral administration of infective third stage larvae (L3) of Nematospiroides dubius to young mice, intestinal worms persist for many weeks. However, in mice injected parenterally with N. dubius adult worms, the intraluminal intestinal infection arising after L3 administration can be terminated within 3 to 4 weeks. This accelerated rejection is seen in sensitized BALB/c mice (and (CBA/H X BALB/c)F1 mice) and in particular females, but has not been demonstrated in sensitized CBA/H mice. In female BALB/c mice, small numbers of living worms are more effective at sensitization than dead worms, intraperitoneal and subcutaneous implantations are both effective, and products from adult worms incubated in vitro (i.e. "excretory/secretory" (ES) products) will sensitize but only with very high doses in adjuvant. Using appropriate isolated antigen preparations, comparative immunoparasitological analyses in different mice should provide clues on the nature of host-protective immunities against intestinal nematode infections which are potentially chronic. From the present studies, two groups which differ most dramatically in the consequences of adult worm sensitization are young male CBA/H versus older female BALB/c mice.

Animals↗

Leucocyte recruitment during enteric nematode infection.

Resolution of infection with the intestinal nematode Trichinella spiralis depends on the host mounting a T helper 2 (Th2) response. It is known that both mast cells and T cells play a crucial role. We have previously shown that efficient migration of mast cells to the gut during infection depends on their expression of the integrin beta 7. beta 7 forms a heterodimer complex with either alpha E or alpha 4 integrin chains, alpha E beta 7 binding to E-cadherin expressed by epithelial cells and alpha 4 beta 7 binding to mucosal addressin cell adhesion molecule (MAdCAM-1) on the endothelium. We were interested to know whether dysfunctional mast cell localization to the gut in the absence of beta 7 was due to the failure of alpha 4 beta 7 to bind to MAdCAM-1 or the failure of alpha E beta 7 to bind to E-cadherin. We used blocking monoclonal antibodies against alpha E (M290) or alpha 4 (PS2) or beta 7 (HB293) during T. spiralis infection of C57BL/6 mice and found that all antibody treatments reduced mastocytosis. In contrast, none of the antibody treatments prevented the migration of CD3(+) T cells into the intestine. These results indicate that during inflammation (a) there is integrin redundancy for lymphocytes but not for mast cells and (b) both alpha E beta 7 and alpha 4 beta 7 are crucial either for the entry of mast cells into the gut or for their maturation once they have entered.

Animals↗

Small intestinal transections decrease the occurrence of tapeworm-induced myoelectric patterns in the rat.

Abstract Luminal infection by the noninvasive tapeworm, H. diminuta, alters rat small intestinal myoelectric activity. The significance of continuity between small intestinal enteric nervous system (ENS) and that of both the stomach/pylorus and colon/caecum regarding the induction of tapeworm-altered myoelectric patterns was evaluated. A total of 32 rats were implanted with four serosal electrodes placed at sites in the duodenum through the mid-jejunum. Sixteen of the 32 rats underwent intestinal transections and anastomoses at both the duodenum and ileum. After recording myoelectrical activity of both normal and transected intestines, eight rats from each group (normal and transected) were infected with H.diminuta. Phase III frequency, duration of the migrating myoelectric complex (MMC), slow wave frequency, percentage of slow waves associated with spike potentials and the occurrence of the the two tapeworm-initiated myoelectric patterns, repetitive bursts of action potentials (RBAP) and sustained spike potentials (SSP), were measured. In infected rats, the frequency of the RBAP and SSP electric patterns were significantly reduced by the double transection. Intestinal transection did not affect the other changes caused by infection, such as decreased MMC phase III frequency and percentage of slow waves associated with spike potentials. In conclusion, a small intestinal ENS in continuity with other segments of the GI tract is required to generate maximal numbers of tapeworm-induced SSP and RBAP myoelectric activity in the small intestine of the rat.

Anastomosis, Surgical↗

Variability of the intestinal immunoglobulin E response of rats to infection with Trichinella spiralis, Heligmosomoides polygyrus or Nippostrongylus brasiliensis.

Total intestinal IgE level increased in rats infected with Trichinella spiralis or Heligmosomoides polygyrus (peak levels of 2.6 microg and 3.7 microg, respectively), but not in rats infected with Nippostrongylus brasiliensis. Intestinal implantation of young adult N. brasiliensis did not stimulate an intestinal immunoglobulin (Ig)E response, suggesting that mucosal penetration may be required for local intestinal IgE responses in rats. During a T. spiralis infection, total IgE levels in the intestinal lumen were consistently higher in LEWIS and LOU rats (rat strains that eliminate T. spiralis worms earlier in the infection) than in PVG, AO and WKA/H strain rats. There was no correlation in either the total level of serum IgE and IgA, or of intestinal IgA with differences between strains in the rate of worm elimination from the gut. Furthermore, the intestinal IgE immunoprecipitated from LEWIS rats 12 days after infection reacted with T. spiralis adult worm metabolic antigens, while intestinal IgE from PVG rats only became reactive with adult worm metabolic antigens from 14 days after infection. These data emphasize the significance of the intestinal IgE response and its unique features by comparison with serum IgE and IgA or intestinal IgA.

Animals↗

The mucosal immune system.

This article outlines the lymphoid structures and cell types important in the intestinal immune response. Particular attention is paid to differences between rodents and man where there appears to be fundamental differences in the sources of the T and B cells which populate the mucosa. The majority of the data still suggest that Peyer's patches are the inductive site of mucosal immunity and the mucosa (lamina propria and epithelium) is the effector site, but there is growing realization that mucosal immune responses can occur in the absence of Peyer's patches and that antigen sampling may also occur in the lamina propria.

Animals↗

[Gastrointestinal strongylosis and malabsorption of nutrients].

The role of malabsorption of nutrients in the mechanism of reduction in productions of the ruminants infested with gastrointestinal nematodes has been a controversial question because of the compensatory absorption and reabsorption in distal part of the small intestine. However, during the last decade, leading research showed that malabsorption has a major role in this mechanism because of 1) compensatory absorption and reabsorption remain limited to some nutrients, 2) large quantities of incompletely digested nutrients exceeding the intestine capacity, and 3) poor reutilization of reabsorbed nutrients.

Animals↗

Intravascular detection of Giardia trophozoites in naturally infected mice. An electron microscopic study.

During routine transmission electron microscopic (TEM) examination of mice naturally infected with Giardia muris, an intense infection with Giardia trophozoites was demonstrated within intestinal and renal tissues. Examination of randomly taken sections from these heavily infected tissues revealed marked deep affection with mixed pathology. Duodenal sections were found loaded with Giardia trophozoites in intimate contact with necrotic gut cells. Some of these trophozoites were detected within central lacteal of damaged villi and nearby blood vessels. Interestingly, and for the first time to be demonstrated, morphologically identical G. muris trophozoite was detected in a renal blood vessel. An intense cellular immune reaction was obviously demonstrated with remarkable interaction between giant macrophages and the trophozoites particulates. Involvement of deep tissues by Giardia trophozoites and their presence within vascular channels could open up questions about the possible invasive and disseminative behavior of G. muris, particularly in heavily and naturally infected hosts.

Animals↗

[Chronic abdominal pain and eosinophilia in a young African patient].

A 20-year-old African female was hospitalized several times for diffuse chronic abdominal pain. The following exclusions were made: Acute adnexitis (by laparoscopy), acute appendicitis (by appendectomy), gastric ulcerations (by esophagogastroduodenoscopy) as well as Crohn's disease and ulcerative colitis. However, once taking a closer microscopical look at the mucosa, that otherwise appeared colonoscopically to be normal, multiple eggs of schistosomiasis mansoni (S. mansoni) were found in the colon as well as the rectum. Thus, the diagnosis of an intestinal bilharziosis was finely established. In retrospect even the sample taken for the appendix could have indicated this diagnosis already earlier on. Both the antibodies (ELISA/IFAT) and the specific immunoglobulins (IgE) for S. mansoni proved significantly positive. Therapy of choice was a single oral dosage of praziquantel. Migration and tourism have considerably increased the range of tropical and infectious diseases that need to be included into differential diagnosis. This case report focuses on intestinal bilharziosis as a potential underlying cause of chronic abdominal pain in immigrants of endemically affected areas. Direct diagnosis is the most important diagnostic method. The adult worms are usually inaccessible, so the method of choice to assess both diagnosis and the degree of activity of a chronic infection is evidence of living eggs in the stool. Alternatively, in case of lack of direct evidence diagnosis can be established by endoscopy and rectal biopsy.

Abdominal Pain↗

[Lambliasis: a cause of malabsorption and diarrhea?].

Multiple biopsies from the lower duodenum were obtained during endoscopy of 171 patients with dyspepsia, diarrhoea and/or suspected malabsorption. Histological evidence of lambliasis was obtained in six (3.5%). Antibiotic treatment with metronidazole, 250 mg two or three times daily for seven to 11 days (which had to be repeated in two cases), improved symptoms in four. In most of the patients "functional upper-abdominal symptoms" had been diagnosed after extensive examinations. In case of unclear upper-abdominal symptoms, chronic or chronic-recurrent diarrhoea and/or malabsorption lambliasis should be considered and histological examination of the duodenal mucosa undertaken.

Adult↗

The effect of intestinal coccidiosis (Eimeria acervulina) on blood and tissue ascorbic acid concentrations.

1. Two experiments were conducted to investigate the effect of intestinal coccidiosis (Eimeria acervulina) on blood plasma and tissue ascorbic acid (AA) concentrations in chicks, and a third experiment was carried out to examine the role of dietary AA in this infection. 2. Experimental infection with intestinal coccidiosis (Eimeria acervulina) brought about a depletion in the concentration of AA in blood plasma, duodenum, jejunum, ileum, liver and the adrenal glands. Generally, these changes were obtained after the prepatent period of 4-5 d of the infection. 3. Dietary AA at 1000 mg/kg prevented the depletion in plasma and tissue AA levels but did not significantly affect adrenal weight.

Adrenal Glands↗

Parameters of intestinal inflammation in mice given graded infections of the nematode Trichinella spiralis.

Four parameters of the intestinal inflammatory response (numbers of mucosal mast cells (MMC) and Paneth cells, villus:crypt ratios and mitotic figures) were measured in mice exposed to varying doses of infective larvae of Trichinella spiralis. The aim of the experiments was to determine whether generation of these components of inflammation required a threshold level of infection and whether, once triggered, inflammation became pan-mucosal. Near maximal MMC and Paneth cell responses were elicited even with infections as low as 35 larvae; changes in villus:crypt ratios and in mitotic indices also occurred at this level of infection, but were progressively greater with increasing levels of infection. In all infected mice, including those infected with 35 larvae, MMC and Paneth cell responses extended over most of the small intestine. These data are interpreted as showing: (i) that the intestinal mucosa is highly responsive to T. spiralis infection; (ii) that once triggered, components of the inflammatory response are amplified by T cell-dependent mechanisms, becoming pan-mucosal; and (iii) that MMC and Paneth cell responses, which require cell division and differentiation, become maximal at a lower infection threshold than changes in the villus:crypt ratio or in mitotic indices, which directly reflect increased rates of division in crypt cells.

Animals↗