Loss Of Mast Cells Research Articles

Lpr-induced systemic autoimmunity is unaffected by mast cell deficiency.

The function of mast cells in allergic and organ-specific autoimmune responses is highly controversial. In the current study, we aimed to dissect the role of mast cells in systemic autoimmunity in the B6(lpr/lpr) mouse, a spontaneous model of systemic lupus erythematosus. B6(lpr/lpr) mice were interbred with C57Bl/6-Kit(W-sh/W-sh) (Wsh) mice, resulting in mast cell deficiency. The offspring from this cross (Lpr/Wsh mice) developed symptoms of lupus of the same severity as B6(lpr/lpr) mice. Loss of mast cells on the Lpr background did not alter autoantibody production, proteinuria, the composition of T and B cell populations or autoimmune pathology. Reduced c-Kit expression did drive expanded splenomegaly and impeded interleukin-4 production by CD4(+) cells, suggesting minor functions for mast cells. In general, we conclude that mast cell deficiency and c-Kit deficiency do not play a role in the pathogenesis of lupus in B6(lpr/lpr) mice.

Mast Cells Are Dispensable for Normal and Activin-Promoted Wound Healing and Skin Carcinogenesis

The growth and differentiation factor activin A is a key regulator of tissue repair, inflammation, fibrosis, and tumorigenesis. However, the cellular targets, which mediate the different activin functions, are still largely unknown. In this study, we show that activin increases the number of mature mast cells in mouse skin in vivo. To determine the relevance of this finding for wound healing and skin carcinogenesis, we mated activin transgenic mice with CreMaster mice, which are characterized by Cre recombinase-mediated mast cell eradication. Using single- and double-mutant mice, we show that loss of mast cells neither affected the stimulatory effect of overexpressed activin on granulation tissue formation and reepithelialization of skin wounds nor its protumorigenic activity in a model of chemically induced skin carcinogenesis. Furthermore, mast cell deficiency did not alter wounding-induced inflammation and new tissue formation or chemically induced angiogenesis and tumorigenesis in mice with normal activin levels. These findings reveal that mast cells are not major targets of activin during wound healing and skin cancer development and also argue against nonredundant functions of mast cells in wound healing and skin carcinogenesis in general.

Increase in nerve fibers and loss of mast cells in polycystic and postmenopausal ovaries

Objective: To quantify nerve fibers and mast cells in human ovaries at different functional stages. Design: Retrospective study. Setting: Research laboratory of the university. Specimen(s): 8 human ovaries in the follicular (cyclic) phase, 7 polycystic ovaries, and postmenopausal ovaries with (n=5) or without (n=7) hyperthecosis. Main Outcome Measure(s): Single- and double immunohistology for the S100 antigen in glial cells of autonomic nerve fibers, for chymase and tryptase in mast cells, and for the common leukocyte antigen on leukocytes. Histometric evaluation was also performed. Intervention(s): None. Result(s): Polycystic ovaries contained significantly more S100-positive nerve fibers in the corticomedullary region than did cyclic ovaries (mean ± SD per 2-mm 2 area, 476 ± 136 and 224 ± 133; P<.01). Postmenopausal ovaries with or without hyperthecosis had the highest density of nerve fibers. In cyclic and polycystic ovaries, more tryptase-positive mast cells than chymase-positive mast cells were found in the interstitial cortex and the medulla. In cyclic ovaries, areas with a moderate density of nerve fibers contained many mast cells. Hence, with increasing nerve fiber density in polycystic ovaries, the number of mast cells decreased strikingly compared with cyclic ovaries ( p<.001). Almost no mast cells were seen in postmenopausal ovaries with and without hyperthecosis. The number of leukocyte antigen–positive leukocytes was similar in all groups. Conclusion(s): The high density of nerve fibers in polycystic and postmenopausal ovaries, together with a conspicuous decrease in mast cells, indicates altered neuroimmune communication.

Treatment of Urticaria Pigmentosa With Corticosteroids

Based on a previous observation that the long-term application of potent topical corticosteroids under occlusion to normal skin resulted in the loss of mast cells, we investigated the effects of intralesional and topical steroids in urticaria pigmentosa (UP). Three patients with UP had lesions that were injected with triamcinolone acetonide. Four weeks after injection, all patients showed a loss of Darier's sign, and, by eight weeks after injection, there was a dramatic clearing of the plaques and a decrease in brown hyperpigmentation. By 12 weeks, mast cells were undetectable by light microscopy and transmission electron microscopy (TEM). The injection sites remained dramatically improved for as long as one year after treatment, and histamine content was reduced 95% in one patient 48 weeks after injection. In six patients, the topical application of 0.05% betamethasone dipropionate under occlusion to limited areas induced almost complete clearing of UP lesions. Lesions treated with an emollient under occlusion, as a control, demonstrated no change. After treatment, no mast cells were seen by light microscopy or TEM, and this persisted for at least 24 weeks. There was also a significant decrease in tissue histamine levels in the treated areas. The treated areas remained clinically improved for at least nine to 12 months. These data indicate that steroid therapy dramatically decreases the excess number of normal-appearing mast cells in UP as well as induces a prolonged resolution of UP lesions. Local corticosteroids thus are a useful therapeutic modality for UP.

Distribution of 5-hydroxytryptamine (5HT) in tissue of a mutant mouse deficient in mast cell (W/Wv). Demonstration of the contribution of mast cells to the 5HT content in various organs.

The content of 5-hydroxytryptamine (5HT) in various tissues of mutant mouse (W/Wv) deficient in mast cells and of control mouse (+/+) was determined by high performance liquid chromatography. The depletion of mast cells in the mutant mouse (W/Wv) was expected to cause a decrease in the 5HT content. In the control mice, 5HT was most densely accumulated in the lung (9.66 +/- 5.23 micrograms/g). Large intestine (6.40 +/- 2.61 micrograms/g) and stomach (6.10 +/- 2.14 micrograms/g) followed the lung in the rating of the 5HT content. The 5HT content of W/Wv mice was only 23.4% and 4.1% that of the control in the stomach (p less than 0.01) and the skin (p less than 0.01), respectively. The results were consistent with the expectation. In other organs (small intestine, caecum, large intestine, brain, lung, blood and salivary gland), the difference between the W/Wv and normal mice was not statistically significant. The difference in the 5HT content of the stomach between the two genotypes was 4.67 micrograms/g and was much larger than the 5HT content (0.49 micrograms/g) of normal mouse skin. With regard to the relatively small number of mast cells present in the stomach, the great difference in the 5HT content in the stomach between the two genotypes cannot be explained by the loss of mast cells. Hence, besides mast cells other cells may contribute to the high 5HT content of the stomach.