open access

Vol 53, No 4 (2015)
Original paper
Published online: 2015-11-19
Submitted: 2015-04-17
Accepted: 2015-11-13
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Pathological study of chronic pulmonary toxicity induced by intratracheally instilled Asian sand dust (Kosa): possible association of fibrosis with the development of granulomatous lesions

Akinori Shimada, Yukari Kohara, Misaki Naota, Yoshimi Kobayashi, Takehito Morita, Kenichiro Inoue, Hirohisa Takano
DOI: 10.5603/fhc.a2015.0030
·
Pubmed: 26615817
·
Folia Histochem Cytobiol 2015;53(4):294-306.

open access

Vol 53, No 4 (2015)
ORIGINAL PAPERS
Published online: 2015-11-19
Submitted: 2015-04-17
Accepted: 2015-11-13

Abstract

Introduction. Exposure to Asian sand dust (ASD) is associated with enhanced pulmonary morbidity and mor­tality, and the reporting of such cases has rapidly increased in East Asia since 2000. The purpose of the study was to assess chronic lung toxicity induced by ASD.

Material and methods. A total of 174 ICR mice were randomly divided into 5 control and 17 exposure groups. Suspensions of low dose (0.2, 0.4 mg) and high dose (3.0 mg) of ASD particles in saline were intratracheally instilled into ICR mice, followed by sacrifice at 24 hours, 1 week, and 1, 2, 3 and 4 months after instillation. Paraffin sections of lung tissues were stained with hematoxylin and eosin and by immunohistochemistry to detect α-smooth muscle actin, collagen III, matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), CD3, CD20, immunoglobulin G, interleukin-1β and inducible nitric oxide synthase.

Results. A lung histological examination revealed similar patterns in the lesions of the groups treated with high (3.0 mg) or low dose (0.4 mg) of ASD. Acute inflammation was observed 24 h after treatment and subsided after 1 week; persistent granulomatous changes were observed at 2 months, focal lymphocytic infiltration at 3 months, and granuloma formation at 4 months. An increase in the size of granulomatous lesions was observed over time and was accompanied by collagen deposition in the lesions. The cytoplasm of macrophages in inflammatory lesions showed positive immunolabeling for MMP-9 at 24 h, 1 and 2 months after instillation of 3.0 mg of ASD. Positive immunolabeling for TIMP-1 was demonstrated in the cytoplasm of macrophages at 2 and 4 months after instillation of 3.0 mg of ASD. These findings suggest association between the expression of MMP-9 and TIMP-1 with the development of lung granulomatous lesions.

Conclusions. These findings suggest that collagen deposition resulting from the altered regulation of extracel­lular matrix is associated with granuloma formation in the lungs of mice treated with ASD.

Abstract

Introduction. Exposure to Asian sand dust (ASD) is associated with enhanced pulmonary morbidity and mor­tality, and the reporting of such cases has rapidly increased in East Asia since 2000. The purpose of the study was to assess chronic lung toxicity induced by ASD.

Material and methods. A total of 174 ICR mice were randomly divided into 5 control and 17 exposure groups. Suspensions of low dose (0.2, 0.4 mg) and high dose (3.0 mg) of ASD particles in saline were intratracheally instilled into ICR mice, followed by sacrifice at 24 hours, 1 week, and 1, 2, 3 and 4 months after instillation. Paraffin sections of lung tissues were stained with hematoxylin and eosin and by immunohistochemistry to detect α-smooth muscle actin, collagen III, matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), CD3, CD20, immunoglobulin G, interleukin-1β and inducible nitric oxide synthase.

Results. A lung histological examination revealed similar patterns in the lesions of the groups treated with high (3.0 mg) or low dose (0.4 mg) of ASD. Acute inflammation was observed 24 h after treatment and subsided after 1 week; persistent granulomatous changes were observed at 2 months, focal lymphocytic infiltration at 3 months, and granuloma formation at 4 months. An increase in the size of granulomatous lesions was observed over time and was accompanied by collagen deposition in the lesions. The cytoplasm of macrophages in inflammatory lesions showed positive immunolabeling for MMP-9 at 24 h, 1 and 2 months after instillation of 3.0 mg of ASD. Positive immunolabeling for TIMP-1 was demonstrated in the cytoplasm of macrophages at 2 and 4 months after instillation of 3.0 mg of ASD. These findings suggest association between the expression of MMP-9 and TIMP-1 with the development of lung granulomatous lesions.

Conclusions. These findings suggest that collagen deposition resulting from the altered regulation of extracel­lular matrix is associated with granuloma formation in the lungs of mice treated with ASD.

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Keywords

Asian sand dust; chronic toxicity; lung; granuloma; MMP-9; TIMP-1; macrophages; CD3; CD20

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About this article
Title

Pathological study of chronic pulmonary toxicity induced by intratracheally instilled Asian sand dust (Kosa): possible association of fibrosis with the development of granulomatous lesions

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 53, No 4 (2015)

Article type

Original paper

Pages

294-306

Published online

2015-11-19

DOI

10.5603/fhc.a2015.0030

Pubmed

26615817

Bibliographic record

Folia Histochem Cytobiol 2015;53(4):294-306.

Keywords

Asian sand dust
chronic toxicity
lung
granuloma
MMP-9
TIMP-1
macrophages
CD3
CD20

Authors

Akinori Shimada
Yukari Kohara
Misaki Naota
Yoshimi Kobayashi
Takehito Morita
Kenichiro Inoue
Hirohisa Takano

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