Intestinal Mast Cells Research Articles

Study of visceral hypersensitivity in irritable bowel syndrome

Visceral hypersensitivity is highly prevalent in most functional bowel disorders, such as irritable bowel syndrome (IBS), and activation of intestinal mast cells (MC) may play a role because they have been found in close proximity to gastrointestinal mucosal sensory nerve terminals containing neuropeptides and a bi-directional pathway connecting the central nervous system, gut, and MC has been demonstrated. The current study appraised the status of rectal visceral perception, as well as the changes in the MC and substance P (SP) in the intestinal mucosa of patients with IBS. The study group comprised 42 patients with IBS and 19 healthy subjects who underwent anorectal manometry and rectal perception thresholds to balloon distension. The MC and the SP-ergic terminals in the mucosa were stained for respective histochemical and immunohistochemical investigations. The results were presented both qualitatively and quantitatively by color image analyzer, based on analysis of the intensity and area of stained fibrils. The structural relationship between the MC and nerve terminals was studied by electron microscopy, using an in situ embedding technique. The anorectal resting pressure, squeezing pressure and relaxation pressure were normal in both groups. The sensation threshold, defecation threshold and pain threshold in diarrhea-predominant IBS and the pain thresholds in constipation-predominant IBS were much lower than in the controls. Rectal compliance decreased in IBS. The number of MC in the terminal ileum, the ileocecal junction and the ascending colon was significantly elevated in IBS (P < 0.01), and the MC showed great variation. A significantly increased concentration of SP was found in the colon of the IBS patients compared with the controls. There was a positive correlation between the profiles of mucosal MC and the SP-ergic terminals, and MC were closely adjacent to SP-ergic terminals in the lamina propria. As altered rectal perception is present in almost all patients with IBS, it might be a reliable biological characteristic of the disease. Alterations in the MC and SP of the intestinal mucosa may be important factors in visceral hypersensitivity.

Increased activity of the intestinal mucosal mast cells in rats with multiple organ failure

This study was undertaken to evaluate the changes in the activity of the intestinal mucosal mast cells (IMMC) in multiple organ failure (MOF). A rat model of MOF was induced by intraperitoneal injection of zymosan. Both the functional alterations and the pathological morphology of essential organs, such as small intestine, liver, kidney and the lungs, were evaluated. The concentrations of histamine and tumor necrosis factor alpha (TNF-alpha) in plasma and small intestinal tissue were detected by fluorimetric assay and enzyme-linked immunosorbent assay, respectively. The ultrastructural changes of the IMMC from the MOF rats were evaluated by transmission electron microscopy. Zymosan induced obvious inflammatory morphology and functional impairment in the essential organs of the rats that were indicative of the characteristic changes in MOF. There was a significantly decreased concentration of histamine in the intestinal tissue of the MOF rats when compared with the normal controls (8.67 +/- 1.16 vs 11.63 +/- 1.97 ng/g protein, P < 0.01), whereas the plasma histamine concentration showed no significant changes. The concentration of TNF-alpha was elevated significantly in both the intestinal tissue and plasma of MOF rats. Furthermore, both the increased number and level of degranulation of the IMMC in the gut tissue was marked in MOF rats. The results suggest that the histamine and TNF-alpha released from activated IMMC play an important role in the development of MOF.

Participation of the intestinal epithelium and mast cells in local mucosal immune responses in commercial poultry

The intestinal mucosa of commercial poultry is continually subjected to invasion or colonization by a wide array of potentially hostile enteric pathogens. Although, recent investigations have focused on lymphocyte involvement in immune responses in the intestine, lymphocyte-mediated immunity alone will not explain the barrier nature of mucosal membranes associated with rejection of many enteric pathogens upon secondary homologous challenge. Our laboratories have focused on nontraditional elements of mucosal immunity in poultry to better understand host-pathogen interactions in the intestine. Following classical and novel immunization procedures, we have identified an antigen-specific mechanism of immediate responsiveness of the mucosal epithelium characterized by epithelial chloride secretion. This mechanism, characteristic of intestinal anaphylaxis, is mediated by local immune elements. Similar mechanisms in mammals contribute to the barrier nature of mucosal membranes during pathogen challenge. To identify cells participating in these and similar responses, additional studies have described a role for mast cells in acute phase responses in the intestines of chickens experimentally challenged with Eimeria. To a more practical end, other experiments in our laboratories have characterized drinking water administration of BSA for elicitation of local and systemic antibody responses. These experiments have shown ad libitum drinking water administration of BSA to be as effective as i.p. administration of BSA; they present a novel approach to immunization of commercial poultry with protein vaccines. These investigations support continued research on host-pathogen interactions within the intestine of commercial poultry to better understand and control enteric pathogens through vaccination or immunomodulation.

Substance P and other neuropeptides do not induce mediator release in isolated human intestinal mast cells.

Neuropeptides such as substance P (SP) and related peptides are supposed to act as mast cell agonists, and thus as mediators of neuroimmune interactions. The data supporting this hypothesis were obtained mostly from rodent experiments. Here, we studied for the first time the effect of SP and other peptides on mediator release in human intestinal mast cells, either unpurified or enriched to 85-99% purity. We found that SP at 0.1-100 micromol L(-1), or other peptides including neurokinin A and B, calcitonin gene-related peptide, vasoactive intestinal peptide and serotonin at 1 micromol L(-1) do not induce release of mediators such as histamine, sulphidoleukotrienes, and tumour necrosis factor alpha. The peptides also failed to cause mediator release in mast cells isolated from inflamed tissue derived from Crohn's disease. Using reverse transcriptase-polymerase chain reaction, flow cytometry and immunohistochemistry, we could show that human intestinal mast cells do not express the tachykinin receptors NK-1, NK-2, or NK-3 under basal conditions. However, upon stimulation by immunoglobulin E (IgE) receptor-crosslinking, which induces an extensive mediator release reaction, a subpopulation of mast cells clearly expressed NK-1, the SP receptor. In conclusion, our data show that SP and other neuropeptides do not act as secretagogues in human intestinal mast cells that have not been pre-activated by IgE receptor-crosslinking.

Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome

Background & Aims : The mechanisms underlying abdominal pain perception in irritable bowel syndrome (IBS) are poorly understood. Intestinal mast cell infiltration may perturb nerve function leading to symptom perception. We assessed colonic mast cell infiltration, mediator release, and spatial interactions with mucosal innervation and their correlation with abdominal pain in IBS patients. Methods : IBS patients were diagnosed according to Rome II criteria and abdominal pain quantified according to a validated questionnaire. Colonic mucosal mast cells were identified immunohistochemically and quantified with a computer-assisted counting method. Mast cell tryptase and histamine release were analyzed immunoenzymatically. Intestinal nerve to mast cell distance was assessed with electron microscopy. Results : Thirty-four out of 44 IBS patients (77%) showed an increased area of mucosa occupied by mast cells as compared with controls (9.2% ± 2.5% vs. 3.3 ± 0.8%, respectively; P < 0.001). There was a 150% increase in the number of degranulating mast cells (4.76 ± 3.18/field vs. 2.42 ± 2.26/field, respectively; P = 0.026). Mucosal content of tryptase was increased in IBS and mast cells spontaneously released more tryptase (3.22 ± 3.48 pmol/min/mg vs. 0.87 ± 0.65 pmol/min/mg, respectively; P = 0.015) and histamine (339.7 ± 59.0 ng/g vs. 169.3 ± 130.6 ng/g, respectively; P = 0.015). Mast cells located within 5 μm of nerve fibers were 7.14 ± 3.87/field vs. 2.27 ± 1.63/field in IBS vs. controls ( P < 0.001). Only mast cells in close proximity to nerves were significantly correlated with severity and frequency of abdominal pain/discomfort ( P < 0.001 and P = 0.003, respectively). Conclusions : Colonic mast cell infiltration and mediator release in proximity to mucosal innervation may contribute to abdominal pain perception in IBS patients.

Intestinal mast cells are increased in a mouse model of eosinophilic gastroenteritis following oral allergen challenge

Rationale Eosinophilic gastroenteritis (EG) is a disease with a poorly understood pathophysiology. Evidence suggests a Th2 mediated allergy to foods. Since mast cells are implicated in immediate hypersensitivity gut reactions, we were interested in examining their participation in EG. Methods 3 week-old BALB/c mice were divided into 3 groups: One group was sensitized by i.p. injection with OVA/alum and then orally challenged twice with soluble OVA [sens/chal]. The second group was only sensitized [sens only] and the third was only challenged [chal only]. Serum OVA specific IgG1 and IgE concentrations were determined by ELISA. IL-4, IL-5 and IFN-γ levels were determined in the supernatants from OVA stimulated splenocyte cultures using ELISA. Jejunal sections were examined for eosinophils by immunohistochemical staining for MBP, and for mast cells by toluidine blue staining. Results Mice in the sens/chal group displayed a Th2 profile, as evidenced by elevated serum IgG1 and IgE, elevated IL-4 and IL-5 and decreased IFN-γ levels in splenocyte supernatants. Histologically, mice in the sens/chal group had more mast cells than the chal only and the sens only groups [35.1 ± 7.6 mast cells/HPF versus 19.0 ± 4.3, p=0.05 and 14.1 ± 5.5, p<0.05 respectively]. This increase paralleled that of the eosinophils [39.7 ± 1.9 eosinophils/HPF versus 16.2 ± 0.4 and 14.0 ± 3.2 respectively]. Numerous mast cells were invading the surface epithelium. Conclusions Oral allergen challenge induced a marked increase in intestinal mast cells in a mouse model of EG. Many were intraepithelial, indicating a possible role of mast cells in the pathophysiology of EG. The model will be used to examine mechanisms underlying this finding.

Local and systemic immune responses to Echinococcus granulosus in experimentally infected dogs

Local and systemic immune responses were studied in six dogs experimentally infected with the dog/sheep tapeworm Echinococcus granulosus. All dogs developed similar IgG antibody response to parasite antigens. In contrast, IgE and IgA responses differed widely. No relationship between IgA responses and parasite burden at the end of the infection were observed. Further, clear differences in the anti-parasite IgA response in serum as compared with specific IgA forming cells in mesenteric lymph nodes were observed within the same dog. An inverse association of anti-parasite IgE and parasite load seemed to be present, with the strongest IgE response in the one dog that had no worms in the intestine at the end of the experiment. No differences were observed in the numbers of intestinal mast cells and goblet cells among all infected dogs. However, the dog with no detectable parasite load had a marked reduction of detected mast cells in the submuscular and muscular layer of the mucosa. Our data give new insight into the immune response of dogs during E. granulosus infection and provide information that may be useful for the rational design of vaccines for the control of hydatid disease.

Involvement of mast cells in basal and neurotensin-induced intestinal absorption of taurocholate in rats.

Neurotensin (NT), a hormone released from intestine by ingested fat, facilitates lipid digestion by stimulating pancreatic secretion and slowing the movement of chyme. In addition, NT can contract the gall bladder and enhance the enterohepatic circulation (EHC) of bile acids to promote micelle formation. Our recent finding that NT enhanced and an NT antagonist inhibited [(3)H]taurocholate ([(3)H]TC) absorption from proximal rat small intestine indicated a role for endogenous NT in the regulation of EHC. Here, we postulate the involvement of intestinal mast cells in the TC uptake process and in the stimulatory effect of NT. In anesthetized rats with the bile duct cannulated for bile collection, infusion of NT (10 pmol.kg(-1).min(-1)) enhanced the [(3)H]TC recovery rate from duodenojejunum by 2.2-fold. This response was abolished by pretreatment with mast cell stabilizers (cromoglycate, doxantrazole) and inhibitors of mast cell mediators (diphenhydramine, metergoline, zileuton). In contrast, mast cell degranulators (compound 48/80, substance P) and mast cell mediators (histamine, leukotriene C(4)) reproduced the effect of NT. N(G)-nitro-l-arginine methyl ester enhanced and l-arginine inhibited basal and NT-induced TC uptake, consistent with the known inhibitory effect of nitric oxide (NO) on mast cell reactivity. These results argue that basal and NT-stimulated TC uptake in rat jejunum are similarly dependent on mast cells, are largely mediated by release of mast cell mediators, and are subject to regulation by NO.

Human intestinal fibroblasts prevent apoptosis in human intestinal mast cells by a mechanism independent of stem cell factor, IL-3, IL-4, and nerve growth factor.

In rodents, fibroblasts (FBs) mediate stem cell factor (SCF)-dependent growth of mast cells (MCs). In humans, SCF is mandatory for MC differentiation and survival. Other factors such as IL-3, IL-4, and nerve growth factor (NGF) act in synergism with SCF, thus enhancing proliferation and/or preventing apoptosis in MCs. In this study, we studied in vitro interactions between human MCs and human FBs, both isolated from the intestine and purified to homogeneity. In coculture with FBs, MCs survived for up to 3 wk, whereas purified MCs cultured alone died within a few days. TNF-alpha and IL-1beta, which both did not affect MC survival directly, enhanced FB-dependent MC growth. We provide evidence that FB-derived MC growth factors are soluble, heat-sensitive molecules which down-regulate MC apoptosis without enhancing MC proliferation. However, only low amounts of SCF were measured in FB-conditioned medium (<0.2 ng/ml). Moreover, blocking of SCF/c-kit interaction by anti-SCF or anti-c-kit Abs and neutralization of IL-3, IL-4, and NGF did not affect MC survival in the coculture system. In conclusion, our data indicate that human FBs promote survival of human MCs by mechanisms independent of SCF, IL-3, IL-4, and NGF. Such interactions between MCs and FBs may explain why MCs accumulate at sites of inflammatory bowel disease and intestinal fibrosis.

Mast cells are required for experimental oral allergen-induced diarrhea.

Gastrointestinal allergic disorders represent a diverse spectrum of inflammatory diseases that are occurring with increasing incidence and severity. An essential question concerning these disorders is to determine the specific cells and mediators responsible for specific clinical manifestations. With this in mind, we developed a murine model of oral allergen-induced intestinal inflammation accompanied by strong Th2-associated humoral and cellular responses and focused on the immunopathogenesis of allergic diarrhea. Exposure of OVA/alum-sensitized mice to repeated doses of intragastric OVA induced genetically restricted, dose-dependent, acute diarrhea associated with increased intestinal permeability, eosinophilia, and mastocytosis. Mice developed limited systemic manifestations of anaphylaxis, even though they developed marked intestinal mucosal mast cell degranulation. Notably, experiments involving mast cell depletion (with anti-c-kit mAb), anti-IgE treatment, and Fc epsilon RI-deficient mice indicated a critical effector role for mast cells in mediating allergic diarrhea. Furthermore, allergic diarrhea was dependent upon synergistic signaling induced by serotonin and platelet-activating factor (PAF), but not histamine. These results demonstrate that oral allergen-induced diarrhea associated with experimental Th2 intestinal inflammation is largely mast cell, IgE, serotonin, and PAF dependent.

Microcirculatory dysfunction during intestinal ischemia-reperfusion.

Oxido-reductive stress is a crucial factor of the tissue response during ischemia-reoxygenation injuries. Reperfusion affects primarily the microvasculature in a manner consistent with an acute inflammatory reaction. In this respect, the salient data suggest an important connection between endothelial cell-derived humoral mediators and the perivascular mast cell system. Increased endothelin-1 and decreased nitric oxide formation, mast cell degranulation and leukocyte accumulation coexist in gastrointestinal ischemia-reperfusion syndromes too. Constitutively produced nitric oxide inhibits, while increasingly formed endothelin-1 significantly enhances the degranulation of the intestinal mast cells. The endothelin-A receptor-dependent mast cell degranulation per se plays a secondary role in reperfusion-induced structural injury, but contributes significantly to leukocyte recruitment into the reperfused intestinal mucosa. It is conceivable therefore, that the nitric oxide--endothelin-1--mast cell cycle is involved in the mechanism of ischemia-reperfusion-induced endothelial cell-leukocyte interactions, where mast cells act to amplify the process of leukocyte sequestration. The alteration in the balance between endothelial cell-derived proadhesive vasoconstrictor and antiadhesive vasodilator factors exerts a significant influence on the mucosal integrity, and the antagonism of endothelin-A receptor activation in this setting tips the equilibrium toward tissue salvage.

Induction of oral tolerance with effects on numbers of IgE-carrying mast cells and on bystander suppression in young rats.

The presence of IgE+ mast cells in the small intestine, bystander suppression of DTH and antibody responses to human serum albumin (HSA) were studied in young rats, made tolerant to ovalbumin (OA) by feeding an OA-containing diet for 1-4 weeks starting from weaning, and in sensitized control rats. One week after finishing the OA diet, both groups of rats were immunized with a mixture of OA and HSA in Freund's complete adjuvant (FCA) at one site on the back. The animals were then colonized for 5 days with a genetically manipulated Escherichia coli producing OA. Immunohistochemical staining of the small intestine of the rats fed the OA diet for 4 weeks showed significantly fewer IgE+ mast cells in the lamina propria, a lower level of MHC class antigen was found in the epithelial cells and in the lamina propria, and the villus crypt depth was also significantly less in tolerant compared with sensitized rats (P = 0.003, 0.007, 0.003, respectively). Sensitized rats showed a mild diarrhoea during the colonization in contrast to tolerant rats. All rats fed OA showed a significantly reduced IgE anti-OA antibody and DTH response to OA before colonization compared with the sensitized rats. Bystander suppression of IgG and IgE anti-HSA antibody responses was also seen, but only in the rats fed OA for either 1 or 4 weeks. Rats fed the OA-containing diet for 1, 3, or 4 weeks showed bystander suppression of the DTH response to HSA. After colonization with E. coli producing OA, rats tolerant to OA after either 1 or 4 weeks on an OA diet maintained tolerance to OA and bystander suppression HSA. These results suggest that oral tolerance to OA down-regulates signs of local inflammatory response by IgE, IgG antibody and T cell responses to OA, but also provides bystander suppression to an unrelated antigen, HSA.

IFN-gamma-independent effects of IL-12 during intestinal nematode infection.

Expulsion of the gastrointestinal nematode Trichinella spiralis is associated with a pronounced mastocytosis mediated by a Th2-type response involving IL-4, IL-10, and IL-13. When exogenous rIL-12 was administered to T. spiralis-infected NIH mice, this resulted in significant suppression of intestinal mast cell responses, delayed worm expulsion, increased muscle larvae burdens, and a transient, but significant decrease in early Th2 cytokine secretion. rIL-12 treatment also altered chemokine expression in the jejunal mucosa. The effects of exogenous IL-12 administration were largely independent of IFN-gamma as shown by rIL-12 treatment of IFN-gamma knockout mice. Hence, IL-12 may play a significant biological role as a direct negative regulator of intestinal Th2 responses and may act to promote the survival of intestinal parasites in vivo also in the absence of IFN-gamma.

Contrasting roles for IL-10 in protective immunity to different life cycle stages of intestinal nematode parasites.

Expulsion of the gastro-intestinal nematode Trichinella spiralis is associated with a pronounced mastocytosis mediated by a T helper (Th) 2 type response involving interleukin (IL)-4 and IL-13. Here we demonstrate that IL-10 is a key regulator of protective immune responses against T. spiralis in vivo. IL-10 knockout mice or normal mice treated with a neutralizing anti-IL-10 receptor antibody are highly susceptible to a primary T. spiralis infection and show significantly delayed adult worm expulsion. Depletion of IL-10 resulted in elevated Th1 and Th2 cytokine responses but significantly reduced numbers of mucosal mast cells in the jejunum. Interestingly, the increase in IFN-gamma detected in the absence of IL-10 resulted in increased immunity to larval stages. Hence, IL-10 has a negative effect on immunity to the tissue dwelling larval stages of T. spiralis but plays a significant biological role as an in vivo regulator of intestinal mast cell responses and is crucially involved in protection against adult stages of intestinal parasites in vivo.

Ascaris suum: cDNA microarray analysis of 4th stage larvae (L4) during self-cure from the intestine

There is spontaneous cure of a large portion of Ascaris suum 4th-stage larvae (L4) from the jejunum of infected pigs between 14 and 21 days after inoculation (DAI). Those L4 that remain in the jejunum continue to develop while those that have moved to the ileum are eventually expelled from the intestines. Although increases in intestinal mucosal mast cells and changes in local host immunity are coincidental with spontaneous cure, the population of L4 that continue to develop in the jejunum may counteract host protective mechanisms by the differential production of factors related to parasitism. To this end, a cDNA library was constructed from L4 isolated from pig jejunum at 21 DAI, and 93% of 1920 original clones containing a single amplicon in the range 400–1500 bp were verified by gel electrophoresis and printed onto glass slides for microarray analysis. Fluorescent probes were prepared from total RNA isolated from: (1) 3rd stage-larvae from lung at 7 DAI, (L3); (2) L4 from jejunum at 14 DAI (L4-14-J); (3) L4 from jejunum at 21 DAI (L4-21-J); (4) L4 from ileum at 21 DAI (L4-21-I, and; (5) adults (L5). Cy3-labeled L3, L4-14-J, L4-21-I and L5 cDNA, and Cy5-labeled L4-21-J cDNA were simultaneously used to screen the printed arrays containing the L4-21-J-derived cDNA library. Several clones showed consistent differential gene expression over two separate experiments and were grouped into 3 distinct transcription patterns. The data showed that sequences from muscle actin and myosin, ribosomal protein L11, glyceraldehyde-3-phosphate dehydrogenase and the flavoprotein subunit of succinate dehydrogenase were highly expressed in L4-21-J, but not in L4-21-I; as were a collection of un-annotated genes derived from a worm body wall-hypodermis library, and a testes germinal zone tissue library. These results suggest that only actively developing A. suum L4 are destined to parasitize the host and successfully neutralize host protective responses. Index Descriptors and Abbreviations: Nematoda; Ascaridoidea; PCR, polymerase chain reaction; RNA, ribonucleic acid; cDNA, complementary deoxyribonucleic acid; SDS, sodium dodecyl sulphate; SSC, saline sodium citrate buffer; TE, Tris:EDTA buffer; PMT, photomultiplier tubes; BLAST, Basic Local Alignment Search Tool; EST, expressed sequence tag; DAI, days after inoculation; L3, A. suum 3rd stage-larvae L4-14-J, 4th stage-larvae from the jejunum at 14 DAI ; L4-21-J, 4th stage-larvae from the jejunum at 21 DAI; L4-21-I, 4th stage-larvae from the ileum at 21 DAI; L5, 5th stage-larvae or young adult; Cy3, cyber green 3; Cy5, cyber red 5; MMC, mucosal mast cell; Th2, T helper cell 2; G3PDH, glyceraldehyde-3-phosphate dehydrogenase; bp, base pairs

Role of activator protein 1, nuclear factor-κB, and nuclear factor of activated T cells in IgE receptor-mediated cytokine expression in mature human mast cells

Background: On activation by cross-linking the high-affinity IgE receptor (FcϵRI), expression of TNF-α, IL-3, IL-5, and IL-13 is induced in human intestinal mast cells. Objective: We sought to examine, for the first time, FcϵRI signaling in mature human mast cells. Methods: Mast cells were isolated from intestinal tissue and cultured in the presence of stem cell factor. The cells were treated with specific inhibitors before stimulation by means of FcϵRI cross-linking. Cytokine mRNA expression was analyzed by means of RT-PCR, and activation of signaling molecules was determined by means of immunocytochemistry, RT-PCR, Western blotting, and protein kinase C (PKC) assay. Results: We found that nuclear factor-κB (NF-κB), as well as c-Fos and c-Jun, the components of activator protein 1 (AP-1), are activated after FcϵRI cross-linking in human intestinal mast cells. Treatment of the cells with specific inhibitors revealed an involvement of NF-κB and nuclear factor of activated T cells, as well as the necessity of extracellular signal-regulated kinase 1/2 (ERK-1/2), PKC, and AP-1 for the induced cytokine gene expression. Consistently, we found that activation of c-Fos corresponds with the induced cytokine gene expression and that ERK-1/2, an activator of c-Fos, was activated in response to FcϵRI cross-linking. Conclusion: Our data on human mast cells show that the activity of ERK-1/2, PKC, and subsequent activation of AP-1 are necessary for the FcϵRI-mediated cytokine expression. Nuclear factor of activated T cells and NF-κB seem to be necessary for the induction of TNF-α, IL-3, and IL-13 but are less important for the transcription of IL-5. (J Allergy Clin Immunol 2003;111:1062-8.)

Murine nippostrongylus brasiliensis (Nb) infection induces changes in intestinal mucosal mast cells (IMMC), IgE levels and afferent nerve activity

Murine nippostrongylus brasiliensis (Nb) infection induces changes in intestinal mucosal mast cells (IMMC), IgE levels and afferent nerve activity

Interleukin-1β and tumor necrosis factor-α enhance human intestinal fibroblast-dependent growth of human intestinal mast cell

Interleukin-1β and tumor necrosis factor-α enhance human intestinal fibroblast-dependent growth of human intestinal mast cell

Animal models in food allergy: assessment of allergenicity and preventive activity of infant formulas

Food allergies occur in about 5–10% of the overall infant and small-child population. Cow's milk protein allergy (CMPA) is the most common in young infants, with a 2–4% incidence. When breastfeeding is not possible, hypoallergenic (HA) cow's milk based formulas are usually given during the first months of life for prevention of CMPA. Depending on primary (sensitization) or secondary (triggering) prevention, the requested quality of HA formulas may be different. Besides in vitro methods, in vivo and ex vivo animal models are helpful in assessing residual allergenicity and the preventive effect of HA formulas. The sensitizing capacity of a formula can be examined by either the parenteral rat (IgE), the guinea pig (IgG1a mediated) or the oral mouse (IgE) models. The triggering IgE mediated allergenicity is tested by a parenteral rat model with oral gavage for intestinal mast cell protease (RMCPII) release. These animal models are also used for testing the oral tolerance inducing capacities of formulas. Together with cellular in vitro assays, animal models are very helpful in predicting allergenicity and the tolerogenic potential of HA infant formulas.

Interferon-gamma reduces survival of human intestinal mast cells and induces MHC class II expression

Interferon-gamma reduces survival of human intestinal mast cells and induces MHC class II expression