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

Arizono, Naoki; Nishida, Motohiro; Uchikawa, Ryuichi; Yamada, Minoru; Matsuda, Shinji; Tegoshi, Tatsuya; Kitamura, Yukihiko; Sasabe, M

doi:10.1046/j.1365-2249.1996.d01-803.x

Cited by 12 publications

(12 citation statements)

References 28 publications

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“…3). This result does not conflict with the fact that eosinophil infiltration into the lung is significantly decreased in Ws/Ws rats infected with N. brasiliensis [23], but suggests that there are two distinct pathways that lead to eosinophilia, i.e., a mast cell-dependent and a mast cell-independent pathway. The presence of two such pathways is supported by the finding that blockade of chymase by SUN-C8257 failed to abrogate blood eosinophilia completely (fig.…”

Section: Discussionmentioning

confidence: 73%

Chymase Inhibitor Ameliorates Eosinophilia in Mice Infected with Nippostrongylus brasiliensis

Watanabe

Miura

Fukuda

2002

Int Arch Allergy Immunol

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Background: Chymase is a chymotrypsin-like serine protease primarily stored in mast cells. Infection with helminth parasites is known to increase the level of mast cell chymase in the jejunum and serum in mice. The aim of the present study is to elucidate the role of chymase in helminth infection. Methods: Chymase inhibitor SUN-C8257 was administered to mice infected with the nematode Nippostrongylus brasiliensis, and the number of eosinophils in the blood, serum IgE levels and fecal egg counts were determined. Results: Administration of SUN-C8257 significantly inhibited blood eosinophilia in BALB/c mice infected with N. brasiliensis. The effect of SUN-C8257 was specific for eosinophils, in that it affected neither the number of total leukocytes nor serum IgE levels. SUN-C8257 did not alter the fecal egg counts in this model, showing that SUN-C8257 has no effect on infectivity and expulsion of the nematode. N. brasiliensis infection induced eosinophilia in mast cell-deficient mice (W/W^v) as well as their littermates (+/+), and SUN-C8257 inhibited the eosinophilia in +/+ mice but not in W/W^v mice. These results suggest that the eosinophil number may be regulated by different mechanisms in W/W^v and +/+ mice, and that the effect of SUN-C8257 on nematode-induced eosinophilia is probably due to chymase inhibition. Conclusions: Chymase released by activated mast cells may play a role in helminth-induced eosinophilia.

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Section: Discussionmentioning

confidence: 73%

Chymase Inhibitor Ameliorates Eosinophilia in Mice Infected with Nippostrongylus brasiliensis

Watanabe

Miura

Fukuda

2002

Int Arch Allergy Immunol

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“…The average numbers of eosinophils as well as EPO levels at 24 and 48 h were slightly lower in WslWs than in +/+ rats, but this difference was not statistically significant. We previously reported that nematode-induced eosinophil infiltration in bronchoalveolar lavage fluid was significantly lower in WslWs than in +/+ rats (17). It was also reported that prior depletion of mast cells in the pleural cavity by local treatment with compound 48/80 significantly reduced antigen-induced eosinophil recruitment in sensitized animals (25).…”

Section: Discussionmentioning

confidence: 90%

Migration of neutrophils is dependent on mast cells in nonspecific pleurisy in rats

Nishida

Uchikawa

Tegoshi

et al. 1999

APMIS

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To determine the role of mast cells in the recruitment of neutrophils and eosinophils, acute nonspecific pleurisy was induced by injecting isologous serum into normal +/+ and mast cell‐deficient Ws/Ws rats. In +/+ rats, neutrophil infiltration peaked 4 h after serum administration, followed by influx of eosinophils after 24–48 h. The levels of neutrophil influx after 4 h as well as the activity of myeloperoxidase (MPO) in pleural lavage‐cell extract were significantly lower in Ws/Ws rats than in +/+ rats. In contrast, numbers of eosinophils as well as activity of eosinophil peroxidase (EPO) did not differ significantly between Ws/Ws and +/+ rats. For local reconstitution of mast cells, +/+ rat peritoneal mast cells (PMC) or mesenteric lymph node cells (MLNC) as a control were transferred into the Ws/Ws pleural cavity. Serum injection into animals with PMC transfer 7 days previously triggered augmented neutrophil influx by approximately 4.7‐fold as compared to that in MLNC‐transferred animals. Mast cells recovered from the pleural cavity of PMC‐transferred rats showed histamine contents equivalent to 20% of that of freshly isolated PMC and retained the reactivity to compound 48/80. These results indicated that dependency of neutrophil recruitment on resident mast cells is greater than that of eosinophils in isologous serum‐induced pleurisy.

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“…These patients usually have elevated IgE antibody levels and symptoms consisting of dyspnea, often of an asthmatic type, suggesting that hypersensitivity mechanisms might be involved in the development of nematode-associated lung lesions (Phills et al, 1972). Like these human parasites, infection with the rodent intestinal nematode Nippostrongylus brasiliensis induces marked infiltration of eosinophils, an increase in the number of alveolar macrophages, development of granulomas, and an increase in the number of mast cells in the lungs In a previous study, we showed that genetically mast cell-deficient Ws/ Ws rats exhibited significantly lower levels of eosinophil infiltration and granuloma formation in the lungs than in normal + / + rats after N. brasiliensis infection, although elevated levels of IgE antibody did not differ between Ws/ Ws and + + rats, suggesting that mast cells play an important role for triggering the lung lesions (Arizono et al, 1996) . In the present study, we further investigated whether an antiallergic drug, ketotifen, would suppress the nematodeinduced lung lesions in rats.…”

Section: Introductionmentioning

confidence: 81%

“…Specific pathogen-free, male Brown Norway (BN/ Sea) rats were purchased from Seiwa Experimental Animals Co. (Fukuoka, Japan) . The animals, 8 weeks old (body weight 180-190 g) , received a subcutaneous injection of 2,000 infective-stage larvae of N. brasiliensis as described previously (Arizono et al, 1996) . A group of animals were sacrificed 28 days after infection.…”

Section: Animals and Nematode Infectionmentioning

confidence: 99%

Ketotifen, an Antiallergic Agent, Suppresses Pulmonary Eosinophilia Induced by the Nematode Nippostrongylus brasiliensis in Rats.

Nishida

Yamada

Uchikawa

et al. 1997

Jap. J. Trop. Med. Hyg.

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Certain parasitic infections such as ascariasis and hookworm diseases occasionally cause a type of Dither's syndrome. This syndrome, which consists of transitory and migratory pulmonary infiltration:with eosinophilia, is presumed to be triggered by hypersensitivity reaction. Previously, we showed thal infection with the nematode Nippostrongylus brasiliensis induces similar lung lesions, that are markedly enhanced after challenge infection. To examine the role of mast cells in ,nematode-induced pneumonitis, N brasiliensis-primed Brown Norway rats received continuous intravenous administration of the mast cer stabilizer ketotifen (6 mg/day/kg body weight) from one day prior to 3 days after challenge infectionSignificantly larger numbers of rat mast cell protease (RMCP) II-positive mast cells were identified in the lungs of ketotifen-administered animals than in saline-perfused animals, suggesting that ketotifen treatment significantly suppressed mast cell activation.Morphological analysis of lung sections showed that ketotifen administration significantly suppressed eosinophil infiltration. Areas of lung granulomas, also triggered by nematode infection, were smaller in ketotifen-treated than in non-treated animals, although this effect was not statistically significant.The worm recoveries from the small intestine did not differ between ketotifentreated and non-treated animals, indicating that the agent did not hinder lung migration of worms. These results suggest that mast cells play an important role at least in the development of mematode-induced lung eosinophilia.

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

Cited by 12 publications

References 28 publications

Chymase Inhibitor Ameliorates Eosinophilia in Mice Infected with <i>Nippostrongylus brasiliensis</i>

Chymase Inhibitor Ameliorates Eosinophilia in Mice Infected with <i>Nippostrongylus brasiliensis</i>

Migration of neutrophils is dependent on mast cells in nonspecific pleurisy in rats

Ketotifen, an Antiallergic Agent, Suppresses Pulmonary Eosinophilia Induced by the Nematode Nippostrongylus brasiliensis in Rats.

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