Quercetin, a naturally occurring flavonol structurally related to the antiallergic drug disodium cromoglycate inhibits anaphylactic histamine release from MMC isolated from the small bowel LP of the rat previously infected with the nematode Nippostrongylus brasiliensis. This contrasts with our previous observation that cromoglycate is inactive in this system. The present effect is immediate and does not decrease on preincubation with the drug. The flavonoids acacetin , apigenin , chrysin , and phloretin also demonstrate significant activity but are less potent than quercetin. Catechin, flavone, morin, and taxifolin are inactive. These results resemble those previously reported for the human basophil. In contrast, all compounds with the possible exception of taxifolin demonstrate significant activity against rat PMC. Acacetin and chrysin are the most effective inhibitors and are more active than quercetin. Rutin (the glycane of quercetin) and phlorezin (the glycane of phloretin) are inactive in both systems. These results are discussed in terms of the functional heterogeneity of mast cells from different sources and identify a group of compounds other than doxantrazole (reported previously), which inhibit histamine secretion by MMC.

Mucosal mast cells: III. Effect of quercetin and other flavonoids on antigen-induced histamine secretion from rat intestinal mast cells

Masl cells have long been recognized as major effector cells of the allergic or lypc I hyperscnsiiivity reaction by virtue of their high-affinity surface receptors for IgE. The wide distribution of mast cells throughout the human body in general, and at mucosai surfaces in particular, in atopic and non-atopic individuals alike, as well as the recognition of mast cell activation by non-immunological means, suggest that these cells also may be involved in non-atopic conditions. Thus, mast cell mediated events have been postulated to play a role in host defenee against parasitic diseases of the intestine, in wound healing and scar formation in lhe skin, and in promoting tumour angiogenesis. The concept of mast cell heterogeneity has emerged as a fundamental principle for the understanding of the possible roles of mast cells in health and disease. Two types ofmast cells are typically recognized, both of which stain metachromatically with cationic dyes such as alcian blue and toluidine blue. The nomenclature used for distinguishing these two types of mast cells varies depending on the species, the tissue source or the biochemical characteristic under study {Table 1). Thus, in the rodent, mucosai and connective tissue types of mast cells are recognized that are also referred to as atypical and typical or formalin sensitive and formalin resistant, respectively. A similar nomenclature has been used in the human. In addition, rodent mast cells have been defined according to their proteoglycan content (H or heparin-containing cells and E or chondroitin sulphate-containing cells) and human mast cells have been defined according to their tissue of origin {lung, skin, gastrointestinal mucosa) and their neutral protease content (T or tryptase-positive, chymase-negative cells, and TC or tryptase-positive. chymase-positive cells).

Mast cell heterogeneity

Chemistry and pharmacology of honey-bee venom

Histamine and the hypothalamus.

There is little or no direct in vivo evidence in man to support the involvement of mast cell-mediator release in the pathogenesis of immediate allergic reactions. We have performed a within-subject controlled study to determine the changes that occur in nasal mast cells during allergen-induced rhinitis. Twelve subjects with asymptomatic rhinitis were studied. Nasal biopsy specimens were obtained from each subject after a control solution (isotonic saline, 0.9% w/v) had been nebulized into one nostril and allergen solution (freeze-dried allergen extract reconstituted with isotonic saline) into the other. The tissues obtained were fixed in Carnoy's solution and stained with the alpha-naphthol AS-D chloroacetate esterase reaction (N AS-D CA ER). Mast cells were counted under light microscopy in the epithelium and lamina propria, and the integrity of each cell was assessed. No significant differences were found in the number of epithelial or lamina propria mast cells in biopsy specimens obtained after saline or allergen administration. However, the number of degranulated mast cells after allergen provocation (89%) was significantly greater than after instillation of control solution (15%) (p = 0.003). Changes of mast cell degranulation after allergen provocation were confirmed by electron microscopy. In six nonatopic, control subjects without rhinitis, there was no significant difference between the percentages of degranulated mast cells after allergen provocation (25.8%) and instillation of saline (24.3%). This study provides direct in vivo evidence for allergen-induced mast cell activation in man.

https://www.jacionline.org/article/0091-6749(86)90082-5/pdf

Direct in vivo evidence for mast cell degranulation during allergen-induced reactions in man.

The systemic responses of different animals to a number of histamine liberators and the effects of these compounds on isolated tissue mast cells in vitro are examined. Mast cells from different species and even from individual tissues within a single animal are shown to vary markedly in their response to given inducers. On this basis, the usefulness of animal models in predicting whether a particular compound may act as a histamine liberator in man is discussed.

F L Pearce

Papers

Functional heterogeneity of mast cells from different species and tissues.