Development and Sequels of Intestinal Inflammation in Nematode-Infected Rats: Role of Mast Cells and Capsaicin-Sensitive Afferents

Objectives: To determine whether intestinal mast cells and capsaicin-sensitive afferent nerves are involved in the development and sequels of Nippostrongylus brasiliensis-induced intestinal inflammation in rats. Methods: Two series of experiments were performed. In the first series, six groups of 8 rats were used to study the effects of mast cell stabilization by ketotifen. In the second series, six groups of 6 rats were used to study the effects of gut extrinsic sensory neuron depletion by capsaicin. For each series, four groups of rats were infected with N. brasiliensis and two groups were not infected. Results: Infection with N. brasiliensis resulted in an increase of myeloperoxidase (MPO) activity and mast cell numbers at day 12 postinfection; MPO returned to preinfection levels by day 35 while mast cell numbers remained elevated at that time. In ketotifen-treated infected rats, the increase of MPO at day 12 was less pronounced, but MPO activity remained elevated and mast cell numbers were increased at day 35. In capsaicin-treated infected rats, the MPO increase at day 12 was augmented, and MPO was still not returned to preinfection values by day 35; in contrast, the increase of mast cell numbers at days 12 and 35 was not modified by afferent nerve depletion. Conclusion: Mast cell stabilization decreased jejunal inflammation during the acute stage (day 12), but prolonged the inflammatory process until at least day 35 postinfection. The data also confirmed the protective role of gut extrinsic sensory neurons against intestinal inflammation in a model of nematode infection and revealed that these afferent nerves do not seem crucial for the development of nematode-induced hypermastocytosis.

[1]  R. Alam,et al.  Histamine release. , 2000, Methods in molecular biology.

[2]  P. Kubes,et al.  Role of inducible nitric oxide synthase in trinitrobenzene sulphonic acid induced colitis in mice , 1999, Gut.

[3]  M. Neurath,et al.  Anti-interleukin 12 treatment regulates apoptosis of Th1 T cells in experimental colitis in mice. , 1999, Gastroenterology.

[4]  F. D’Acquisto,et al.  Evidence that mast cell degranulation, histamine and tumour necrosis factor α release occur in LPS‐induced plasma leakage in rat skin , 1999, British journal of pharmacology.

[5]  Zhi-Li Huang,et al.  Activation of sensory nerves participates in stress-induced histamine release from mast cells in rats , 1999, Neuroscience Letters.

[6]  K. Takeuchi,et al.  Nitric oxide, superoxide radicals and mast cells in pathogenesis of indomethacin-induced small intestinal lesions in rats. , 1999, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[7]  V. Théodorou,et al.  Protective role of vagal afferents in experimentally-induced colitis in rats. , 1998, Journal of the autonomic nervous system.

[8]  C. Pothoulakis,et al.  Direct evidence of mast cell involvement in Clostridium difficile toxin A-induced enteritis in mice. , 1998, Gastroenterology.

[9]  L. Buéno,et al.  Brain Fos expression and intestinal motor alterations during nematode-induced inflammation in the rat. , 1998, American journal of physiology. Gastrointestinal and liver physiology.

[10]  S. Crowe,et al.  Mast cell mediated ion transport in intestine from patients with and without inflammatory bowel disease , 1997, Gut.

[11]  P. Mclean,et al.  Effects of nematode infection on sensitivity to intestinal distension: role of tachykinin NK2 receptors. , 1997, European journal of pharmacology.

[12]  D. Rachmilewitz,et al.  Sulphydryl blocker induced small intestinal inflammation in rats: a new model mimicking Crohn’s disease , 1997, Gut.

[13]  R. Stead,et al.  Vagal afferent nerve fibres contact mast cells in rat small intestinal mucosa. , 1997, Neuroimmunomodulation.

[14]  M. Brezis,et al.  The effect of ketotifen on nitric oxide synthase activity , 1997, British journal of pharmacology.

[15]  R. Stead,et al.  Effect of truncal vagotomy and capsaicin on mast cells and IgA‐positive plasma cells in rat jejunal mucosa , 1997, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[16]  J. Schwartz,et al.  Functional relationships between sensory nerve fibers and mast cells of dura mater in normal and inflammatory conditions , 1997, Neuroscience.

[17]  R. Stead,et al.  Nippostrongylus brasiliensis infection evokes neuronal abnormalities and alterations in neurally regulated electrolyte transport in rat jejunum , 1996, Parasitology.

[18]  C. Sternini,et al.  Action of sensory neurons in an experimental at colitis model of injury and repair. , 1996, The American journal of physiology.

[19]  N. Arizono,et al.  Cytokine mRNA expression profiles in rats infected with the intestinal nematode Nippostrongylus brasiliensis , 1995, Infection and immunity.

[20]  S. Galli,et al.  Mast‐cell—leukocyte cytokine cascades in allergic inflammation , 1995, Allergy.

[21]  S. Galli,et al.  Stem cell factor contributes to intestinal mucosal mast cell hyperplasia in rats infected with Nippostrongylus brasiliensis or Trichinella spiralis, but anti-stem cell factor treatment decreases parasite egg production during N brasiliensis infection. , 1995, Blood.

[22]  J. Wallace,et al.  Nitric oxide synthesis inhibition increases epithelial permeability via mast cells. , 1994, The American journal of physiology.

[23]  C. Goso,et al.  Topical capsaicin administration protects against trinitrobenzene sulfonic acid-induced colitis in the rat. , 1993, European journal of pharmacology.

[24]  P. Kubes,et al.  Nitric oxide syni hesis inhibition induces leukocyte adhesion via superoxid and mast cells , 2004 .

[25]  R. Eliakim,et al.  Ketotifen inhibits Clostridium difficile toxin A-induced enteritis in rat ileum. , 1993, Gastroenterology.

[26]  L. Buéno,et al.  Involvement of capsaicin-sensitive afferent nerves in the intestinal motor alterations induced by intestinal anaphylaxis in rats. , 1993, International archives of allergy and immunology.

[27]  R. Eliakim,et al.  Ketotifen effectively prevents mucosal damage in experimental colitis. , 1992, Gut.

[28]  J. Wallace,et al.  Capsaicin-induced hyperemia in the stomach: possible contribution of mast cells. , 1992, The American journal of physiology.

[29]  R. Stead Innervation of mucosal immune cells in the gastrointestinal tract. , 1992, Regional immunology.

[30]  D. Agrawal,et al.  The effect of ketotifen on eosinophils as measured at LTC4 release and by chemotaxis. , 1991, Allergy proceedings : the official journal of regional and state allergy societies.

[31]  P. Holzer Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. , 1991, Pharmacological reviews.

[32]  R. Eliakim,et al.  Gastric mucosal damage by ethanol is mediated by substance P and prevented by ketotifen, a mast cell stabilizer. , 1991, Gastroenterology.

[33]  P. Sherman,et al.  Benefit of ketotifen in patients with eosinophilic gastroenteritis. , 1991, The American journal of medicine.

[34]  T. Mosmann,et al.  Interleukin 10: a novel stimulatory factor for mast cells and their progenitors , 1991, The Journal of experimental medicine.

[35]  H. Nolte,et al.  Histamine release from gut mast cells from patients with inflammatory bowel diseases. , 1990, Gut.

[36]  Y. Kojima,et al.  Anatomical variation in mast cell nerve associations in the rat small intestine, heart, lung, and skin. Similarities of distances between neural processes and mast cells, eosinophils, or plasma cells in the jejunal lamina propria. , 1990, Laboratory investigation; a journal of technical methods and pathology.

[37]  N. Arizono,et al.  Bromodeoxyuridine labeling studies on the proliferation of intestinal mucosal mast cells in normal and athymic rats , 1990, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[38]  K. Taniguchi,et al.  Inhibitions of metabolic responses of polymorphonuclear leukocytes by antiallergic drugs. , 1989, Journal of pharmacobio-dynamics.

[39]  N. Arizono,et al.  Kinetics and staining properties of mast cells proliferating in rat small intestine tunica muscularis and subserosa following infection with Nippostrongylus brasiliensis , 1988, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[40]  R. Hunt,et al.  Changes in intestinal permeability and epithelial differentiation during inflammation in the rat. , 1988, Gut.

[41]  K. Beyreuther,et al.  Characterization of a T cell-derived lymphokine that acts synergistically with IL 3 on the growth of murine mast cells and is identical with IL4 , 1987 .

[42]  R. Stead,et al.  Intestinal mucosal mast cells in normal and nematode-infected rat intestines are in intimate contact with peptidergic nerves. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[43]  J. Bienenstock The role of mast cell in inflammatory processes : Evidence of nerve/mast cell interaction , 1987 .

[44]  K. Beyreuther,et al.  Characterization of a T cell-derived lymphokine that acts synergistically with IL 3 on the growth of murine mast cells and is identical with IL 4. , 1987, Immunobiology.

[45]  R. Stead,et al.  The role of mast cells in inflammatory processes: evidence for nerve/mast cell interactions. , 1987, International archives of allergy and applied immunology.

[46]  F. Lorente,et al.  Action of ketotifen on different functions of neutrophil polymorphonuclear cells. , 1986, Allergologia et immunopathologia.

[47]  D. Wakelin,et al.  Mucosal mast cells are functionally active during spontaneous expulsion of intestinal nematode infections in rat , 1984, Nature.

[48]  D. Priebat,et al.  Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. , 1982, The Journal of investigative dermatology.

[49]  Y. Kitamura,et al.  Prolonged infection of nippostrongylus brasiliensis in genetically mast cell-depleted w/wv mice. , 1980 .