Mucosal mast cells

Bronchial Asthma. Figure 2 Mechanisms of bronchial hyperresponsiveness. Toxic products from eosinophils [cationic peptides, reactive oxygen species (ROS)] cause epithelial injury. Nerve endings become easily accessible to mediators from mast cells, eosinophils [eosinophil-derived neurotoxin (EDN)], and neutrophils, and to airborne toxicants such as S02. Activation of nerve endings stimulates effector cells like mucosal glands and airway smooth muscle either directly or by cholinergic reflexes. 

Chymase (mast cell protease type II), a chymotrypsin-like protease, is a serine protease found in mucosal mast cells, which catalyzes the conversion of angiotensin I to angiotensin II and of big endothelin 1 (ET1) to ET1 (1-31). 

Scudamore, C.L., Thornton, E.M., McMillan, L., Newlands, G.F.J. and Miller, H.R.P. (1995) Release of the mucosal mast cell granule chymase, rat mast cell protease-II, during anaphylaxis is associated with the rapid development of paracellular permeability to macromolecules in rat jejunum. Journal of Experimental Medicine 182, 1871—1881. 

The mechanisms whereby mast cells enhance host protection to H. polygyms and T. spiralis (and whether these are related to the leak-lesion hypothesis) have not yet been fully defined. Certainly, mast cells contribute to intestinal inflammation during infection through the secretion of a range of cytokines (Gordon et al., 1990) and vasoactive substances (see above). In addition, the release of mast cell proteases are known to increase enterocyte permeability to macromolecules in the rat intestine (Scudamore et al., 1995) and regulate epithelial cell functions at other mucosal sites (Cairns and Walls, 1996). 

Lee, T.D.G. and Wakelin, D. (1982) The use of host strain variation to assess the significance of mucosal mast cells in the spontaneous cure response of mice to the nematode Trichuris muris. International Archives of Allergy and Applied Immunity 67, 302—305. 

Abe, T. and Nawa, Y. (1988) Worm expulsion and mucosal mast cell response induced by repetitive IL-3 administration in Strongyloides ratti-infected nude mice. Immunology 63, 181-185. 

Khan, A.I., Horii, Y., Tiuria, R., Sato, Y. and Nawa, Y. (1993) Mucosal mast cells and the expulsive mechanisms of mice against Strongybides venezuelensis. InternationalJournal of Parasitology 23, 551-555. 

Koyama, K. and Ito, Y. (2000) Mucosal mast cell responses are not required for protection against infection with the murine nematode parasite Trichuris muris. Parasite Immunology 22, 21—28. 

Perdue, M.H., Ramage,J.K., Burget, D., Marshall, J. and Masson, S. (1989) Intestinal mucosal injury is associated with mast cell activation and leukotriene generation during Nippostrongylus-induced inflammation in the rat. Digestive Disease Science 34, 724—731. 

Wang, C.H., Korenaga, M., Greenwood, A. and Bell, R.G. (1990) T-helper subset function in the gut of rats differential stimulation of eosinophils, mucosal mast cells and antibody-forming cells by OX8 OX22 and OX8 OX22+ cells. Immunology 71, 166-175. 

Mast cell degranulation in response to allergens results in release of mediators such as histamine eosinophil, and neutrophil chemotactic factors leukotrienes C4, D4, and E4 prostaglandins and platelet-activating factor (PAF). Histamine is capable of inducing smooth muscle constriction and bronchospasm and may play a role in mucosal edema and mucus secretion. 

Substance P, calcitonin-gene-related peptide (CGRP), and neurokinin A have been identified by immunocytochemistry in primary sensory neurones and in cutaneous sensory nerve terminals and these are often in close proximity to mast cells [54, 56], For example, in Lewis rats that were infected with the parasitic larvae of Nippostrongylis brasiliensis in order to induce a proliferation of mucosal mast cells, nearly two-thirds of the lamina propria mast cells were in intimate contact with peptidergic nerves containing SP and CGRP, while an additional 20% of the mast cells were within 2 gm [54], All three peptides are... 

Table 4.1. IDENTIFIED PEPTIDES AFFECTING MAST-CELL FUNCTION See text for appropriate references unless otherwise indicated, RPMC, rat peritoneal mast cell RMMC, rat mucosal mast cell MBMC, murine bone-marrow derived.

SP seems to be the only peptide capable of stimulating histamine release from mucosal mast cells [52] and generally exhibits a pronounced heterogeneity among various tissues and between species [106],... 

Recently, NGF has been shown to cause a significant proliferation of connective tissue mast cells when injected subcutaneously into newborn (day 1) rats [122]. This effect of NGF is blocked by DSCG, which suggests that products released from NGF-stimulated mast cells are responsible (directly or indirectly) for the proliferation or recruitment of other mast cells. In adult rats, a similar proliferation of mucosal mast cells in the small intestine is known to accompany an infection by intestinal nematode, N. brasilensis [123] and has also been reported to accompany the repeated injections of compound 48/80 [ 124], It may be relevant in this regard that mast cells are frequently prominent in a wide variety of fibrotic conditions such as neurofibromatosis where itching around the growing neurofibroma is a common symptom [125]. Treatment of neurofibromatosis with ketotifen, a mast cell stabilizer similar to DSCG, results... 

Dynorphin, a-neoendorphin and /1-endorphin each produced a dose-dependent (10 6 M to 10 4 M) release of histamine from rat peritoneal mast cells but not from rat mucosal mast cells which were isolated following collagenase digestion [128]. When administered intradermally to the forearms of human volunteers, dynorphin, /f-endorphin, Leu-enkephalin and morphiceptin each produced a wheal and flare reaction at nM concentrations. Mast cell degranulation was confirmed by electron microscopy of biopsy samples and by its inhibition by hyroxyzine pretreatment [129]. 

Interleukin-3 (IL-3), a glycoprotein lympokine from T cells, stimulates the growth of murine mast cells, neutrophils, and macrophages from haemopoietic progenitor cells [71,153]. Thus, cultures of murine bone marrow or spleen cells supplemented with IL-3 have been shown to generate cells that have many of the characteristics of mucosal mast cells [71, 153]. The release of IL-3 in vivo... 

Srinivasan et al. (2006) continuation of Srinivasan et al., 1996) Same study population 10 CD subjects who supplemented GFD with 50 g oats/day for 3 months Immune responses of in vitro duodenal mucosal culture treated with Abs against HLA D-related, Ki-67, CD25, CD54, ICAM-1, and mast cell tryptase None of the patients developed clinical or lab evidence of adverse effects Distribution of intestinal HLA-DR expression was not affected Number of CD25 and tryptase positive cells was not altered Distribution and intensity of ICAM-1 staining unchanged No evidence of immune activation from oats supplementation... 

Cellular pathophysiology of asthma. Top, Cross-section of the normal airway and the asthmatic ain/vay. Mediators released during the inflammatory process associated with asthma cause bronchoconstriction, mucus secretion, and mucosal inflammation and edema. These changes reduce the size of the airway lumen and increase resistance to airflow, which leads to wheezing and shortness of breath. Bottom, The multitude of inflammatory cells (macrophages, eosinophils, mast cells, neutrophils) and neurotransmitters implicated in asthma pathophysiology. 

Hemmerich, S. Pecht, I. Oligomeric structure and autophosphorylation of nucleoside diphosphate kinase from rat mucosal mast cells. Biochemistry, 31, 4580-4587 (1992)... 

Pearce, F. L., Befus, A. D., and Bienenstock, J. Mucosal mast cells. III. Effect of quercetin and other flavonoids on antigen-induced histamine secretion from rat intestinal mast cells. J Allergy Clin Immunol, 73(6), 819-823, 1984. 

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