Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously reported that intestinal mast cells represent a separate population of mast cells which is thymus- (T-) dependent. In this paper we examine whether the appearance of these cells is dependent on thymus-dependent antibodies or thymus serum factor(s). The response of intestinal mast cells and globule leucocytes to a Trichinella spiralis infection was therefore studied in congenitally athymic (nude) mice after treatment with specific anti-T. spiralis hyperimmune serum or normal mouse serum from thymus-bearing litter-mates. However, transfer of both types of serum did not lead to an intestinal mast cell response. It was concluded that the presence of an intact thymus or T-dependent cellular reactions and/or their products are essential for appearance of intestinal mast cells. In contrast infected athymic mice reacted with a minor reponse of globule leucocytes irrespective of the serum transfer. Occasionally metachromatic intra-epithelially located cells with toluidine-blue-positive granules, believed to be globule leucocytes, showed mitotic figures. Metachromatic cells were observed occasionally within the lumen of the gut. These data were interpreted as supporting the idea that the globule leucocyte is a cell sui generis and independent of the intestinal mast cell.
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PMID:Response of intestinal globule leucocytes in the mouse during a Trichinella spiralis infection and its independence of intestinal mast cells. 31 2

The mast cell response in the mucosa and connective tissue of 36 jejunal biopsies of patients with clinically diagnosed trichinellosis, teniasis and lambliasis has been studied. Biopsy material was fixed in standard formalin or Carnoy's fixative, enabling differentiation between mucosal mast cells (MMC) and connective tissue mast cells (CTMC). With both fixatives CTMC could equally well be recognized. With Carnoy's fixative an additional population of mast cells (MMC) could be visualized both in the mucosa and the connective tissue. In the mucosa small mucosal mast cells were observed as well. Compared to the numbers of mast cells in the mucosa and the connective tissue of teniasis and lambliasis patients, the number of mast cells in trichinellosis patients only visualized using Carnoy's fixative was markedly higher. It was concluded that also in man trichinellosis is accompanied by an increase of cells with MMC characteristics. Further studies are needed to clarify the morphological and histochemical features of these cells and their possible role in this parasitic infection.
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PMID:Increase of mucosal mast cells in the jejunum of patients infected with Trichinella spiralis. 686 61

The duration of primary infections with T. spiralis was dose-dependent with greater proportional loss of worms from heavily infected hamsters and longer persistence of worms in syngeneic DSN hamsters carrying initially low intensity infections. Intestinal worms were lost more rapidly from challenged immunized animals with over 80% loss of established worms by day 6 post infection, but survival of residual worms for a further 2 weeks. Hamsters carrying initially more than 140 intestinal worms began to lose weight during the second week indicating severe pathology at this stage of infection. Mucosal mast cell numbers increased from 50 cells/20 villus crypt units in uninfected animals to a peak in excess of 150 during week 4 pi, although intestinal mastocytosis persisted long after the loss of the majority of adult worms. Serum antibody responses to muscle stage larval antigen were detected in week 3 and increased subsequently. Both mastocytosis and antibody responses were more intense on secondary exposure to infection. Hamsters vaccinated with muscle stage larval antigen showed only a moderately accelerated loss of the intestinal phase but the fecundity of worms was severely suppressed. Overall it was concluded that the hamster host provided a model of trichinellosis that, in many respects was closer than mice and rats to the pattern of infection seen in economically and clinically important host species.
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PMID:The response of hamsters to primary and secondary infection with Trichinella spiralis and to vaccination with parasite antigens. 770 73

We analysed the cytokine profile of a T cell subset (CD4+ CD45 RC-) that confers protection against Trichinella spiralis infection in rats. These CD4+ cells are generated in the gut and appear in the thoracic duct lymph within 72 h after infection. Cytokine mRNA levels for IL-2, IL-3, IL-4, IL-5, IL-10 and IFN-gamma and functional cytokine secretion for IL-4, IL-5, IFN-gamma, TNF-alpha and mast cell differentiation activity were tested in vitro following stimulation with T. spiralis antigens. Compared to a non-protective T cell population (CD4+ CD45 RC+ or CD8+), also isolated from the same thoracic lymph, no significant differences were observed in the levels of mRNA for IL-2, IL-3, IL-4, IL-5, IL-10 or IFN-gamma in the protective CD4+ CD45 RC- cells. However, analysis of the cytokine activities in culture supernatant of these T cell subsets following 24 h stimulation in vitro with T. spiralis antigens showed that significant IL-4 and IL-5 activity but little IFN-gamma or TNF-alpha was secreted by the protective CD4+ CD45- RC- cells. Whereas the non-protective CD4+ CD45 RC+ cells secreted significant levels of IL-4, IFN-gamma, mast cell differentiating activity and TNF-alpha but little IL-5 activity. Non-protective CD8+ cells were found to secrete IL-4 but not IL-5. Production of IL-4 was essentially equal for both protective and non-protective T cell subsets. These findings suggest that the presence or absence of IFN-gamma secretion, rather than IL-4 alone, determines whether a T cell subset has protective activity against T. spiralis infection in rats.
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PMID:Cytokine profile of protective anti-Trichinella spiralis CD4+ OX22- and non-protective CD4+ OX22+ thoracic duct cells in rats: secretion of IL-4 alone does not determine protective capacity. 780 64

Alcohol consumption has been shown to be associated with immune suppression and immune modulation. In this study, the effects of ethanol ingestion on the host immune responses to Trichinella spiralis infection and the subsequent secretion of T-helper cell-associated cytokines were investigated in rats. At the early phase of T. spiralis infection, ethanol-fed animals showed decreased numbers of blood neutrophils and eosinophils, and a decreased secretion of interferon-gamma (IFN-gamma) by mesenteric lymph node cells, compared with pair-fed controls. Suppression of this early inflammatory response to infection in the ethanol-treated groups resulted in a slower rate of expulsion of intestinal adult worms and a higher fecundity rate for female worms, compared with pair-fed controls. A dramatic decrease in blood neutrophils in the ethanol-treated groups was also manifested on day 9 postinfection. At that time, mesenteric lymph node cells from the ethanol-treated groups secreted higher amounts of mast cell proliferation-enhancing activity, which has been shown to contain T-helper type 2-associated cytokines. At the later phase of infection (day 12 to 20 day postinfection), ethanol-treated animals contained higher numbers of blood eosinophils and secreted an increased amount of interleukin-5 and mast cell proliferation-enhancing activity, compared with pair-fed controls. Although there was a slight rise with time after infection, the level of serum corticosterone was not significantly increased in the ethanol groups. Therefore, it is not likely that the observed immune modulations caused by ethanol consumption, especially in the early phase of infection, is the effect of elevated levels of corticosterone in the circulation. The present study found that ethanol consumption suppressed the initial amount of interferon-gamma secretion and inflammatory response, and may have directly or indirectly led to an enhancement of the secretion of T-helper type 2-type cytokines later in the primary immune response to T. spiralis infection.
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PMID:Ethanol consumption suppresses cell-mediated inflammatory responses and increases T-helper type 2 cytokine secretion in Trichinella spiralis-infected rats. 934 76

The ontogeny and function of gut-associated-lymphoid tissue is known to be critically dependent on the beta7 integrin subfamily. We have investigated the development of intestinal inflammation and pathogen-specific protective immunity to enteric helminth infection in beta7 integrin knockout (KO) mice. During Trichinella spiralis infection of the small intestine there was a significant delay and reduction in the magnitude of intestinal eosinophilia and mastocytosis in the absence of P7 integrin, resulting in impaired host protection. Aberrant distribution of mast cells was also observed in the small intestine of infected KO mice. Adoptive transfer of primed wild-type mesenteric lymph node cells into T. spiralis-infected beta7 KO mice did not restore the intestinal mast cell response, suggesting that the defect in intestinal mastocytosis is due to the absence of beta7 expression on this population rather than an indirect consequence of reduced T cell numbers. In contrast, no impairment in leukocyte recruitment or protection against Trichuris muris infection of the large intestine was observed in KO mice. Taken together the data provide the first description of reduced leukocyte homing and attenuated protective immunity against helminth infection in beta7 KO mice. Furthermore, these results suggest that beta7 integrin-independent adhesion molecule interactions are deployed in the large but not small intestine during intestinal inflammation.
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PMID:Beta7 integrin-deficient mice: delayed leukocyte recruitment and attenuated protective immunity in the small intestine during enteric helminth infection. 1089 2

We have investigated the influence of mast cells on the barrier function of intestinal epithelium during nematode infection. Trichinella spiralis infection induces a strong type 2 cytokine-mediated inflammation, resulting in a critical mucosal mastocytosis that is known to mediate expulsion of the parasites from the intestine. The host response to infection is also characterized by an increase in mucosal leakiness. We show here that intestinal epithelial permeability is markedly elevated during infection, with kinetics that mirror the adaptive immune response to primary and secondary infection. Furthermore, we have identified degradation of the tight junction protein, occludin, thereby providing a mechanism for increased paracellular permeability during helminth infection. We further demonstrate by using anti-c-kit antibody and IL-9 transgenic mice that mast cells are directly responsible for increasing epithelial paracellular permeability and that mice deficient in a mast cell-specific protease fail to increase intestinal permeability and fail to expel their parasite burden. These results provide the mechanism whereby mucosal mast cells mediate parasite expulsion from the intestine.
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PMID:Mast cells disrupt epithelial barrier function during enteric nematode infection. 1279 12

The intestinal protozoan parasite Giardia lamblia causes diarrhoea in humans and animals. In the present study, we used the C57BL/6 inbred mouse model to assess the impact of a nematode (Trichinella spiralis) infection on the course of a G. lamblia (clone GS/M-83-H7) infection. Acute trichinellosis coincided with transient intestinal inflammation and generated an intestinal environment that strongly promoted growth of G. lamblia trophozoites although the local anti-Giardia immunoglobulin (Ig) A production was not affected. This increased G. lamblia infection intensity correlated with intestinal mast cell infiltration, mast cell degranulation, and total IgE production. Furthermore, a G. lamblia single-infection investigated in parallel also resulted in intestinal mast cell accumulation but severe infiltration was triggered in the absence of IgE. Recently, intestinal mast cells emerging during a G. lamblia infection were reported to be involved in those immunological mechanisms that control intestinal proliferation of the parasite in mice. This anti-giardial activity was assumed to be related to the capacity of mast cells to produce IL-6. However, this previous assumption was questioned by our present immunohistological findings indicating that murine intestinal mast cells, activated during a G. lamblia infection were IL-6-negative. In the present co-infection experiments, mast cells induced during acute trichinellosis were not able to control a concurrent G. lamblia infection. This observation makes it feasible that the T. spiralis infection created an immunological and physiological environment that superimposed the anti-giardial effect of mast cells and thus favoured intestinal growth of G. lamblia trophozoites in double-infected mice. Furthermore, our findings raise the possibility that intestinal inflammation e.g. as a consequence of a 'pre-existing' nematode infection is a factor which contributes to increased susceptibility of a host to a G. lamblia infection. The phenomenon of a 'pre-existing' nematode infection prior to a G. lamblia infection is a frequent constellation in endemic areas of giardiasis and may therefore have a direct impact on the epidemiological situation of the disease.
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PMID:Acute trichinellosis increases susceptibility to Giardia lamblia infection in the mouse model. 1667 42

Trichinella spiralis infection in rats induces hypermotility and an abnormal response to cholecystokinin (CCK) similar to motor disturbances observed in irritable bowel syndrome. Mast cell hyperplasia is also characteristic of this experimental model. The aim of our study was to correlate mast cell activity with the development of dysmotility and to demonstrate whether the mast cell stabilizer ketotifen [4-(1-methyl-4-piperidylidene)-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-10(9H)-one fumarate] could prevent the development of intestine hypermotility. Sprague-Dawley rats were infected with T. spiralis and, 5 days after infection, treated with the mast-cell stabilizer ketotifen (10 mg/kg/day). Twelve days after infection, intestinal spontaneous motor activity and response to CCK were evaluated by means of strain-gauge transducers. Immunohistochemistry for rat mast cell protease II (RMCPII), cyclooxygenase (COX)-2, and inducible nitric-oxide synthase (iNOS) was performed in intestinal specimens. In addition, RMCPII and myeloperoxidase were determined in serum. Infected control rats showed hypermotility, mast cell hyperplasia, increased RMCPII levels, increased myeloperoxidase, and overexpression of COX-2 and iNOS. In contrast, ketotifen-treated rats showed spontaneous intestinal motility and CCK response similar to the noninfected control rats. Mast cell hyperplasia and RMCPII were reduced in ketotifen-treated rats. Inflammatory parameters were less modified by ketotifen, but those animals that received the longest ketotifen treatment showed a slight amelioration in these parameters. These results indicate that mast cells are implicated in the development of hypermotility. The treatment with ketotifen prevented hypermotility and mast cell hyperplasia and diminished mucosal mast cell activity.
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PMID:Mast cell stabilizer ketotifen [4-(1-methyl-4-piperidylidene)-4h-benzo[4,5]cyclohepta[1,2-b]thiophen-10(9H)-one fumarate] prevents mucosal mast cell hyperplasia and intestinal dysmotility in experimental Trichinella spiralis inflammation in the rat. 1698 56

Trichinella spiralis infection causes hyperexcitability in enteric after-hyperpolarising (AH) sensory neurons that is mimicked by neural, immune or inflammatory mediators known to stimulate adenylyl cyclase (AC)/cyclic 3',5'-adenosine monophosphate (cAMP) signaling. The hypothesis was tested that ongoing modulation and sustained amplification in the AC/cAMP/phosphorylated cAMP related element binding protrein (pCREB) signaling pathway contributes to hyperexcitability and neuronal plasticity in gut sensory neurons after nematode infection. Electrophysiological, immunological, molecular biological or immunochemical studies were done in T. spiralis-infected guinea-pigs (8000 larvae or saline) after acute-inflammation (7 days) or 35 days p.i., after intestinal clearance. Acute-inflammation caused AH-cell hyperexcitability and elevated mucosal and neural tissue levels of myeloperoxidase, mast cell tryptase, prostaglandin E2, leukotrine B4, lipid peroxidation, nitric oxide and gelatinase; lower level inflammation persisted 35 days p.i. Acute exposure to blockers of AC, histamine, cyclooxygenase or leukotriene pathways suppressed AH-cell hyperexcitability in a reversible manner. Basal cAMP responses or those evoked by forskolin (FSK), Ro-20-1724, histamine or substance P in isolated myenteric ganglia were augmented after T. spiralis infection; up-regulation also occurred in AC expression and AC-immunoreactivity in calbindin (AH) neurons. The cAMP-dependent slow excitatory synaptic transmission-like responses to histamine (mast cell mediator) or substance P (neurotransmitter) acting via G-protein coupled receptors (GPCR) in AH neurons were augmented by up to 2.5-fold after T. spiralis infection. FSK, histamine, substance P or T. spiralis acute infection caused a 5- to 30-fold increase in cAMP-dependent nuclear CREB phosphorylation in isolated ganglia or calbindin (AH) neurons. AC and CREB phosphorylation remained elevated 35 days p.i.. Ongoing immune activation, AC up-regulation, enhanced phosphodiesterase IV activity and facilitation of the GPCR-AC/cAMP/pCREB signaling pathway contributes to T. spiralis-induced neuronal plasticity and AH-cell hyperexcitability. This may be relevant in gut nematode infections and inflammatory bowel diseases, and is a potential therapeutic target.
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PMID:Cyclic AMP signaling contributes to neural plasticity and hyperexcitability in AH sensory neurons following intestinal Trichinella spiralis-induced inflammation. 1730 83


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