Anemia and mast cell depletion in mutant rats that are homozygous at "white spotting (Ws)" locus

Self Cite

SUMMARYCertain nematode infections induce eosinophil infiltration and granulomatous responses in the lungs. To examine the role of mast cells in the development of lung lesions, normal = and genetically mast cell-deficient Ws/Ws rats were infected with the nematode Nippostrongylus brasiliensis. In = rats, numbers of eosinophils in bronchoalveolar lavage fluid (BALF) increased significantly 3-7 days after infection, and granulomatous responses composed of histiocytes/macrophages and multinucleate giant cells were triggered in the lungs 3-14 days after infection. Challenge infection, which was carried out on day 28 after primary infection, induced much higher levels of granulomatous response than after primary infection, suggesting that the response is mediated at least in part by an immunological mechanism. In Ws/Ws rats, both the eosinophil percentage in BALF and the size of the granulomas in the lungs were significantly smaller than in = rats after primary as well as after challenge infection. The amount of rat mast cell protease (RMCP) II in = rat BALF was increased 1 day after primary infection and more significantly after challenge infection, suggesting that lung mucosal mast cells were activated more markedly after the challenge infection. In Ws/Ws rats, RMCP II was undetectable throughout the observation period. The time course of nematode migration in the lungs did not differ in = and Ws/Ws rats. These results suggest that mast cell activation might be relevant to eosinophil infiltration and granulomatous response in the lungs, although the responses do not affect lung migration of the nematode.

“…Ws/Ws and = rats were produced as described previously [15]. Ws/Ws and = rats, 8-10 weeks of age, received a subcutaneous injection of 2000 infective-stage larvae of N. brasiliensis.…”

Section: Animals and Nematode Infectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Lung granulomatous response induced by infection with the intestinal nematode Nippostrongylus brasiliensis is suppressed in mast cell-deficient Ws/Ws rats

Arizono

Nishida

Uchikawa

et al. 1996

Self Cite

“…The role of mast cell activation was evaluated in mast cell-de®cient Ws/Ws (white spotting in the skin) rats. Ws/Ws rats have a 12-base deletion in the tyrosine kinase domain of the c-kit cDNA, and are genetically de®cient in both connective tissue-type (CTMC) and MMC [11]. These rats are useful for studying the role of mast cells in the pathogenesis of IBD.…”

Section: Introductionmentioning

confidence: 99%

Development of dextran sulphate sodium-induced experimental colitis is suppressed in genetically mast cell-deficient Ws/Ws rats

Araki

Andoh

Fujiyama

et al. 2000

Ws/Ws rats have a small deletion of the c-kit gene, and are deficient in both mucosal-type mast cells (MMC) and connective tissue-type mast cells (CTMC). In the present study we investigated the role of intestinal MMC in the development of dextran sulphate sodium (DSS)-induced experimental colitis using Ws/Ws rats. Ws/Ws and control (+/+) rats were given a 3% DSS aqueous solution orally for 10 days, and the subsequent mucosal damage was evaluated macroscopically and histologically. The mucosal myeloperoxidase (MPO) activities and histamine levels were also measured. (i) DSS induced severe oedema and hyperaemia with sporadic erosions in the control (+/+) rats, but these changes were significantly attenuated in the Ws/Ws rats (P < 0.01). (ii) The microscopic mucosal damage score was lower in the Ws/Ws rats than in the control (+/+) rats (P = 0.06). (iii) There were no significant differences in mucosal MPO activity between the Ws/Ws and control (+/+) rats (P = 0.46). (iv) The mucosal histamine levels in the colon were significantly reduced in the Ws/Ws rats compared with the control (+/+) rats (P < 0.05). (v) Significant positive correlations were observed between mucosal histamine levels and the degree of mucosal oedema (calculated as colonic wet weight/protein content) (r = 0.778, P < 0.01), and between histamine levels and the macroscopic damage (r = 0.623, P < 0.05), respectively. (vi) DSS induced a local recruitment of MMC in the colonic mucosa of Ws/Ws rats, and mucosal damage gradually increased in accordance with this MMC recruitment. These results indicate that MMC play an important role in the development of DSS colitis.

“…Ws/Ws and control (þ/þ) rats were purchased from Japan SLC, Inc. (Shizuoka, Japan), and these animals were checked as free of parasites. The origin of Ws/Ws rats has been described in detail [7,8]. Experiments were performed on male Ws/Ws or control (þ/ þ) rats (200-250 g) anaesthetized with sodium pentobarbital (Nakalai, Kyoto, Japan).…”

Section: Surgical Preparationmentioning

confidence: 99%

“…The purpose of the present study was to elucidate the role of MMC activation in the induction of rapid mucosal barrier dysfunction after I/R treatment. This was mainly evaluated by experiments using genetically mast celldeficient Ws/Ws (white spotting in the skin) rats [7][8][9]. Ws/Ws rats have a 12-base deletion in the tyrosine kinase domain of the ckit cDNA and are deficient in both connective tissue type and mucosal type mast cells.…”

Section: Introductionmentioning

confidence: 99%

Rapid intestinal ischaemia-reperfusion injury is suppressed in genetically mast cell-deficient Ws/Ws rats

Andoh

Kimura

Fukuda

et al. 1999

Ws/Ws rats have a small deletion of the c-kit gene, and are deficient in both mucosal and connective tissue-type mast cells. In this study, the role of mucosal type mast cells (MMC) in the development of intestinal ischaemia-reperfusion injury was investigated in Ws/Ws rats. Autoperfused segments of the jejunum were exposed to 60 min of ischaemia, followed by reperfusion for various time periods. The epithelial permeability was then assessed by the 51Cr-EDTA clearance rate. In the control (+/+) rats, the maximal increase in mucosal permeability was achieved at 45 min of reperfusion. In contrast, this increase was significantly and potently attenuated in the Ws/Ws rats. Mucosal alkaline phosphatase activity decreased in the control (+/+) rats, but was not altered in the Ws/Ws rats. There were no differences in mucosal myeloperoxidase activity, indicating that granulocytes did not contribute to tissue injury. These results provide direct evidence for the role of mast cells in the pathogenesis of intestinal ischaemia-reperfusion injury.