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Noto CN, Hoft SG, DiPaolo RJ. Mast Cells as Important Regulators in Autoimmunity and Cancer Development. Front Cell Dev Biol 2021; 9:752350. [PMID: 34712668 PMCID: PMC8546116 DOI: 10.3389/fcell.2021.752350] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 09/17/2021] [Indexed: 01/04/2023] Open
Abstract
Mast cells are an essential part of the immune system and are best known as important modulators of allergic and anaphylactic immune responses. Upon activation, mast cells release a multitude of inflammatory mediators with various effector functions that can be both protective and damage-inducing. Mast cells can have an anti-inflammatory or pro-inflammatory immunological effect and play important roles in regulating autoimmune diseases including rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. Importantly, chronic inflammation and autoimmunity are linked to the development of specific cancers including pancreatic cancer, prostate cancer, colorectal cancer, and gastric cancer. Inflammatory mediators released from activated mast cells regulate immune responses and promote vascular permeability and the recruitment of immune cells to the site of inflammation. Mast cells are present in increased numbers in tissues affected by autoimmune diseases as well as in tumor microenvironments where they co-localize with T regulatory cells and T effector cells. Mast cells can regulate immune responses by expressing immune checkpoint molecules on their surface, releasing anti-inflammatory cytokines, and promoting vascularization of solid tumor sites. As a result of these immune modulating activities, mast cells have disease-modifying roles in specific autoimmune diseases and cancers. Therefore, determining how to regulate the activities of mast cells in different inflammatory and tumor microenvironments may be critical to discovering potential therapeutic targets to treat autoimmune diseases and cancer.
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Affiliation(s)
- Christine N Noto
- Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis University, St. Louis, MO, United States
| | - Stella G Hoft
- Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis University, St. Louis, MO, United States
| | - Richard J DiPaolo
- Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, Saint Louis University, St. Louis, MO, United States
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Weiler CR. Mast Cell Activation Syndrome: Tools for Diagnosis and Differential Diagnosis. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2020; 8:498-506. [DOI: 10.1016/j.jaip.2019.08.022] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Revised: 07/30/2019] [Accepted: 08/07/2019] [Indexed: 02/07/2023]
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Parambeth JC, López FR, Lopez R, Keyser SB, Lidbury JA, Suchodolski JS, Steiner JM. Fecal Concentrations of N-methylhistamine in Common Marmosets ( Callithrix jacchus). Comp Med 2019; 69:130-134. [PMID: 30803469 DOI: 10.30802/aalas-cm-18-000040] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Chronic lymphocytic enteritis (CLE) is a frequent disease in common marmosets. However, no diagnostic test for early detection of CLE is available. Mast cells have an important role in gastrointestinal disease. The purpose of this study was to measure fecal concentrations of N-methylhistamine (NMH), a breakdown product of histamine metabolism, in common marmosets. A previously established NMH gas chromatography-mass spectrometry assay for canine feces and urine was used, and partial validation was performed. The reference intervals (n = 30) established for fecal NMH concentrations in common marmoset were 118.2 ng/g or less for a single fecal sample, 121.7 ng/g or less for the 3-d mean, and less than or equal to 167.5 ng/g for the 3-d maximum. Considerable day-to-day variation was observed in fecal NMH concentrations; the mean %CV was 42.2% (minimum, 7.1%; maximum, 141.4%). Fecal NMH concentrations were measured in 14 marmosets for which necropsy reports were available; 7 of the 8 marmosets with CLE and the 1 animal with lymphoma and ulcerative enteritis had increased fecal NMH concentrations. Increased fecal NMH concentrations may serve as a potential marker for CLE; however, further studies exploring the role of mast cells in marmosets with CLE are needed.
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Affiliation(s)
- Joseph Cyrus Parambeth
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary and Biomedical Sciences;,
| | - Franklin R López
- Veterinary Medical Diagnostic Laboratory, Center for Bioinformatical and Genomic Systems Engineering, Texas A and M University, College Station, Texas
| | - Rosana Lopez
- Engineering Experiment Station, Center for Bioinformatical and Genomic Systems Engineering, Texas A and M University, College Station, Texas
| | - Sarah B Keyser
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary and Biomedical Sciences
| | - Jonathan A Lidbury
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary and Biomedical Sciences
| | - Jan S Suchodolski
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary and Biomedical Sciences
| | - Jörg M Steiner
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary and Biomedical Sciences
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Anfinsen KP, Berghoff N, Priestnall SL, Suchodolski JS, Steiner JM, Allenspach K. Urinary and faecal N-methylhistamine concentrations do not serve as markers for mast cell activation or clinical disease activity in dogs with chronic enteropathies. Acta Vet Scand 2014; 56:90. [PMID: 25528646 PMCID: PMC4288550 DOI: 10.1186/s13028-014-0090-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2014] [Accepted: 12/12/2014] [Indexed: 11/20/2022] Open
Abstract
Background This study sought to correlate faecal and urinary N-methylhistamine (NMH) concentrations with resting versus degranulated duodenal mast cell numbers in dogs with chronic enteropathies (CE), and investigate correlations between intestinal mast cell activation and clinical severity of disease as assessed by canine chronic enteropathy clinical activity index (CCECAI), and between urinary and faecal NMH concentrations, mast cell numbers, and histopathological scores. Twenty-eight dogs with CE were included. Duodenal biopsies were stained with haematoxylin and eosin (H&E), toluidine blue, and by immunohistochemical labelling for tryptase. Duodenal biopsies were assigned a histopathological severity score, and duodenal mast cell numbers were counted in five high-power fields after metachromatic and immunohistochemical staining. Faecal and urinary NMH concentrations were measured by gas chromatography–mass spectrometry. Results There was no correlation between the CCECAI and faecal or urinary NMH concentrations, mast cell numbers, or histopathological score – or between faecal or urinary NMH concentration and mast cell numbers. Post hoc analysis revealed a statistically significant difference in toluidine blue positive mast cells between two treatment groups (exclusion diet with/without metronidazole versus immunosuppression (IS)), with higher numbers among dogs not requiring IS. Conclusion Faecal and urinary NMH concentrations and duodenal mast cell numbers were not useful indicators of severity of disease as assessed by the CCECAI or histological evaluation. The number of duodenal mast cells was higher in dogs that did not need IS, i.e. in dogs responding to an exclusion diet (with/without metronidazole), than in dogs requiring IS. Further studies comparing the role of mast cells in dogs with different forms of CE are needed.
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Berghoff N, Hill S, Parnell NK, Mansell J, Suchodolski JS, Steiner JM. Fecal and urinary N-methylhistamine concentrations in dogs with chronic gastrointestinal disease. Vet J 2014; 201:289-94. [PMID: 24907867 DOI: 10.1016/j.tvjl.2014.05.016] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2013] [Revised: 04/24/2014] [Accepted: 05/11/2014] [Indexed: 01/01/2023]
Abstract
Due to their ability to release inflammatory mediators, such as histamine, mast cells are potentially important in gastrointestinal disease. The purpose of this study was to measure N-methylhistamine (NMH), a histamine metabolite, in fecal and urine samples from dogs with chronic gastrointestinal disease. Fecal and urinary NMH concentrations were compared between dogs with chronic gastrointestinal disease and control dogs, and/or to control ranges. Correlation between fecal and urinary NMH concentrations, serum C-reactive protein (CRP) concentration, the clinical disease activity index (CCECAI), and gastrointestinal mucosal mast cell numbers (where available) in dogs with gastrointestinal disease was evaluated. Seven of 16 dogs with gastrointestinal disease had increased urinary or fecal NMH concentrations, but there was no correlation between NMH concentrations and the CCECAI or mucosal mast cells numbers. Urinary NMH concentrations were positively associated with histological grading and serum CRP concentrations. The lack of correlation between NMH concentrations and the CCECAI suggests that NMH may not be a good marker for clinical disease activity in dogs as determined by the CCECAI. Based on their association with severity of intestinal mucosal inflammation, urinary NMH concentrations may potentially have clinical utility as a marker of intestinal inflammation in certain groups of dogs with chronic gastrointestinal disease, but future studies in a larger number of dogs are necessary to further characterize the role of mast cell-mediated inflammation in dogs with chronic gastrointestinal disease.
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Affiliation(s)
- Nora Berghoff
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, 4474 TAMU, Texas A&M University, College Station, TX 77843, USA; Clinical Pathology Laboratory - DCPAH, Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, A 215 Veterinary Medical Center, 736 Wilson Rd, East Lansing, MI 48824-1314, USA.
| | - Steve Hill
- Veterinary Specialty Hospital, 10435 Sorrento Valley Rd, San Diego, CA 92121, USA
| | - Nolie K Parnell
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, 625 Harrison Street, West Lafayette, IN 47907, USA
| | - Joanne Mansell
- Department of Pathobiology, College of Veterinary Medicine and Biomedical Sciences, 4474 TAMU, Texas A&M University, College Station, TX 77843, USA
| | - Jan S Suchodolski
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, 4474 TAMU, Texas A&M University, College Station, TX 77843, USA
| | - Jörg M Steiner
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, 4474 TAMU, Texas A&M University, College Station, TX 77843, USA
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Berghoff N, Steiner JM. Laboratory tests for the diagnosis and management of chronic canine and feline enteropathies. Vet Clin North Am Small Anim Pract 2011; 41:311-28. [PMID: 21486638 DOI: 10.1016/j.cvsm.2011.01.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Chronic enteropathies are commonly encountered in both cats and dogs. Although definitive diagnosis often requires collection of gastrointestinal biopsies for histopathologic evaluation, less invasive laboratory tests can be highly informative and should be performed prior to biopsy collection. Tests for determination of infectious causes comprise those for helminthic, protozoal, bacterial, or fungal organisms. Intestinal function and disease may be assessed by measuring serum concentrations of cobalamin, folate, and C-reactive protein, and fecal concentrations of α(1)-proteinase inhibitor. Ongoing research has led to development of tests for serum perinuclear antineutrophilic cytoplasmic antibodies, and fecal inflammatory markers, including S100-proteins and N-methylhistamine.
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Affiliation(s)
- Nora Berghoff
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, Texas A&M University, 4474 TAMU, College Station, TX 77843, USA.
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López Palacios N, Agúndez JAG, Mendoza JL, García-Martín E, Martínez C, Fuentes Ferrer ME, Ladero JM, Taxonera C, Díaz-Rubio M. Analysis of a non-synonymous single nucleotide polymorphism of the human diamine oxidase gene (ref. SNP ID: rs1049793) in patients with Crohn's disease. Scand J Gastroenterol 2010; 44:1207-12. [PMID: 19670078 DOI: 10.1080/00365520903171250] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To analyse the possible influence of a non-synonymous single nucleotide polymorphism (SNP) of the histamine-degrading enzyme diamine oxidase (DAO) on genetic susceptibility to Crohn's disease (CD). MATERIAL AND METHODS In this prospective, case-control study, 210 unrelated Caucasian consecutive CD patients were recruited at the Inflammatory Bowel Disease Unit of a single tertiary centre (Hospital Clínico San Carlos) in Madrid, Spain. A total of 261 healthy volunteers from the same geographic area were also recruited and matched with patients. Both cases and controls were analysed for the presence of a non-synonymous SNP (rs1049793) of DAO using amplification-restriction procedures of the genotype obtained in a blood sample. RESULTS No significant differences were found in the distribution of carriers of the non-synonymous SNP of DAO between CD patients and controls (OR 1.2 (95% CI 0.9-1.6; p=0.3)). Nor were any differences found between carriers and non-carriers of the non-synonymous SNP in demographic characteristics, phenotypes, complications or treatment of CD. CONCLUSIONS The study of a non-synonymous SNP (rs1049793) of DAO does not seem to be of use in assessing susceptibility to CD, either as a marker of disease activity or as a marker of clinical behaviour in patients with the disease.
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Affiliation(s)
- Natalia López Palacios
- Service of Gastroenterology, Hospital Clínico San Carlos, Complutense University, Madrid, Spain.
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García-Faroldi G, Sánchez-Jiménez F, Fajardo I. The polyamine and histamine metabolic interplay in cancer and chronic inflammation. Curr Opin Clin Nutr Metab Care 2009; 12:59-65. [PMID: 19057189 DOI: 10.1097/mco.0b013e328314b9ac] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
PURPOSE OF REVIEW To provide an update on the major research contributing to deciphering the metabolic interplay of polyamines/histamine and its impact in cancer and chronic inflammation. RECENT FINDINGS The most recent and relevant findings that might reflect a link between the polyamines/histamine metabolic interplay and the development of cancer and chronic inflammation-related diseases include: the observation that histamine catabolism is downregulated in the colonic mucosa of patients with colonic adenoma; the finding that some polyamine and histamine-related metabolites are different between a breast cancer cell line and a reference mammary epithelial cell line; and the demonstration of the critical role that mast cells (a cell type in which the polyamine/histamine metabolic interplay has been confirmed) play in the development of pancreatic tumors. There is still, however, a lack of specific studies elucidating the exact contribution of the polyamine/histamine metabolic interplay in these clinical settings. SUMMARY In mammalian cells, a polyamine/histamine metabolic interplay has been extensively proven; however, its ultimate effect on human health largely depends on the cell type and environment. Information on this topic is currently fragmented in the literature. In order to develop efficient intervention strategies, it will be necessary to establish an integrated and holistic view of the role of the polyamine/histamine metabolic interplay in each pathological state.
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Affiliation(s)
- Gianni García-Faroldi
- Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, and CIBER de Enfermedades Raras, Campus de Teatinos s/n, Málaga, Spain
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Anti-Inflammatory mechanisms of enteric Heligmosomoides polygyrus infection against trinitrobenzene sulfonic acid-induced colitis in a murine model. Infect Immun 2008; 76:4772-82. [PMID: 18644879 DOI: 10.1128/iai.00744-07] [Citation(s) in RCA: 61] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Recent studies showed that enteric helminth infection improved symptoms in patients with inflammatory bowel disease as well as in experimental models of colitis. The aim of this study was to determine the mechanism of the protective effect of helminth infection on colitis-induced changes in immune and epithelial cell function. BALB/c mice received an oral infection of Heligmosomoides polygyrus third-stage larvae, were given intrarectal saline or trinitrobenzene sulfonic acid (TNBS) on day 10 postinfection, and were studied 4 days later. Separate groups of mice received intrarectal saline or TNBS on day 10 and were studied on day 14. Muscle-free colonic mucosae were mounted in Ussing chambers to measure mucosal permeability and secretion. Expression of cytokines was assessed by quantitative real-time PCR, and mast cells were visualized by immunohistochemistry. TNBS-induced colitis induced mucosal damage, upregulated Th1 cytokines, and depressed secretory responses. Heligmosomoides polygyrus elevated Th2 cytokine expression, increased mast cell infiltration and mucosal resistance, and also reduced some secretory responses. Prior H. polygyrus infection prevented TNBS-induced upregulation of Th1 cytokines and normalized secretory responses to specific agonists. TNBS-induced colitis did not alter H. polygyrus-induced mast cell infiltration or upregulation of Th2 cytokine expression. The results indicate that the protective mechanism of enteric nematode infection against TNBS-induced colitis involves prevention of Th1 cytokine expression and improved colonic function by a mechanism that may involve mast cell-mediated protection of neural control of secretory function. Similar response patterns could account for the clinical improvement seen in inflammatory bowel disease with helminthic therapy.
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Kuefner MA, Schwelberger HG, Hahn EG, Raithel M. Decreased histamine catabolism in the colonic mucosa of patients with colonic adenoma. Dig Dis Sci 2008; 53:436-42. [PMID: 17562176 DOI: 10.1007/s10620-007-9861-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2006] [Accepted: 04/30/2007] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Alterations in mucosal histamine degradation play an important role in various gastrotinestinal diseases including colonic adenoma. In humans, histamine can be catabolized either by oxidative deamination by diamine oxidase (DAO) or by ring methylation by histamine N-methyltransferase (HNMT). The significance of HNMT in this context was investigated for the first time in this project. METHODS About 94 colonic biopsies were endoscopically obtained from 23 patients suffering from colonic adenoma and 26 biopsies from six healthy individuals. Each sample was mechanically homogenized, homogenates were cleared by centrifugation and used for determination of protein and histamine concentrations and enzyme activities of DAO and HNMT by radiometric assay. RESULTS In adenoma patients DAO activities were slightly and HNMT activities were significantly decreased in normal mucosa compared to controls. Activities of both enzymes were significantly lower in adenoma tissue than in healthy mucosa in the same patients. A significant correlation was found between HNMT and DAO in all investigated samples. Histamine concentrations were elevated in adenoma patients. CONCLUSIONS Histamine catabolism is decreased in the colonic mucosa of patients with colonic adenoma.
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Affiliation(s)
- Michael A Kuefner
- Radiologisches Institut, Universität Erlangen-Nürnberg, Maximiliansplatz 1, 91054 Erlangen, Germany.
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Bischoff SC, Gebhardt T. Role of Mast Cells and Eosinophils in Neuroimmune Interactions Regulating Mucosal Inflammation in Inflammatory Bowel Disease. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2006; 579:177-208. [PMID: 16620019 DOI: 10.1007/0-387-33778-4_12] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Stephan C Bischoff
- Division of Clinical Nutrition/Prevention and Immunology, University of Hohenheim, Stuttgart, Germany
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Abstract
Mast cell has a long history of being recognized as an important mediator-secreting cell in allergic diseases, and has been discovered to be involved in IBD in last two decades. Histamine is a major mediator in allergic diseases, and has multiple effects that are mediated by specific surface receptors on target cells. Four types of histamine receptors have now been recognized pharmacologically and the first three are located in the gut. The ability of histamine receptor antagonists to inhibit mast cell degranulation suggests that they might be developed as a group of mast cell stabilizers. Recently, a series of experiments with dispersed colon mast cells suggested that there should be at least two pathways in man for mast cells to amplify their own activation-degranulation signals in an autocrine or paracrine manner. In a word, histamine is an important mediator in allergic diseases and IBD, its antagonists may be developed as a group of mast cell stabilizers to treat these diseases.
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Affiliation(s)
- Hua Xie
- Allergy and Inflammation Research Institute, Shantou University Medical College, 22 Xin-Ling Road, Shantou 515031, Guangdong Province, China
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Abstract
Historically, mast cells were known as a key cell type involved in type I hypersensitivity. Until last two decades, this cell type was recognized to be widely involved in a number of non-allergic diseases including inflammatory bowel disease (IBD). Markedly increased numbers of mast cells were observed in the mucosa of the ileum and colon of patients with IBD, which was accompanied by great changes of the content in mast cells such as dramatically increased expression of TNF-α, IL-16 and substance P. The evidence of mast cell degranulation was found in the wall of intestine from patients with IBD with immunohistochemistry technique. The highly elevated histamine and tryptase levels were detected in mucosa of patients with IBD, strongly suggesting that mast cell degranulation is involved in the pathogenesis of IBD. However, little is known of the actions of histamine, tryptase, chymase and carboxypeptidase in IBD. Over the last decade, heparin has been used to treat IBD in clinical practice. The low molecular weight heparin (LMWH) was effective as adjuvant therapy, and the patients showed good clinical and laboratory response with no serious adverse effects. The roles of PGD2, LTC4, PAF and mast cell cytokines in IBD were also discussed. Recently, a series of experiments with dispersed colon mast cells suggested there should be at least two pathways in man for mast cells to amplify their own activation-degranulation signals in an autocrine or paracrine manner. The hypothesis is that mast cell secretogogues induce mast cell degranulation, release histamine, then stimulate the adjacent mast cells or positively feedback to further stimulate its host mast cells through H1 receptor. Whereas released tryptase acts similarly to histamine, but activates mast cells through its receptor PAR-2. The connections between current anti-IBD therapies or potential therapies for IBD with mast cells were discussed, implicating further that mast cell is a key cell type that is involved in the pathogenesis of IBD. In conclusion, while pathogenesis of IBD remains unclear, the key role of mast cells in this group of diseases demonstrated in the current review implicates strongly that IBD is a mast cell associated disease. Therefore, close attentions should be paid to the role of mast cells in IBD.
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Affiliation(s)
- Shao-Heng He
- Allergy and Inflammation Research Institute, Medical College, Shantou University, Shantou 515031, Guangdong Province, China.
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Abstract
Fibrosis is a serious complication of Crohn disease for which there is no effective therapy. It is unclear why fibrosis, particularly fibrosis of the mucosal layer, develops in Crohn disease and not in ulcerative colitis. Smooth muscle cells, subepithelial myofibroblasts, and fibroblasts have traditionally been considered mediators of fibrosis, but new information points to a role of interstitial cells of Cajal and mast cells. Recent evidence about the role of each of these cell types in fibrosis in Crohn disease or other inflammatory bowel diseases is described. Hypothetical models to describe how altered function of these cells could underlie fibrosis of the mucosa or submucosal layers are presented. Fibrosis is not well characterized in any animal model of inflammatory bowel disease. The merits of several animal models for defining the mechanisms of inflammation-induced intestinal fibrosis are reviewed.
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Affiliation(s)
- P K Lund
- Department of Cell and Molecular Physiology and Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7545, USA.
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