Involvement of mast cell chymase in bleomycin-induced pulmonary fibrosis in mice

Tomimori, Yoshiaki; Muto, Tsuyoshi; Saito, Kieko; Tanaka, Taisaku; Maruoka, Hiroshi; Sumida, Motoo; Fukami, Hironobu; Fukuda, Yoshiaki

doi:10.1016/j.ejphar.2003.08.050

Cited by 51 publications

(41 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Altogether, our data indicate that MCs can modulate the early inflammatory phase, but they play only a limited role in the development of late fibrosis in this lung injury model. Consistent with the role of MCs observed at day 7 in our study, two independent reports indicated that administration of the chymase inhibitors NK3201 or SUN C8077 dose-dependently inhibits BLM-induced lung fibrosis in mice (16,17). Indeed, MC chymase expression is increased in the lungs of humans with idiopathic pulmonary fibrosis (15).…”

Section: Discussionsupporting

confidence: 77%

“…Previous reports show that inhibitors of MC chymase can significantly reduce BLM-induced inflammation and fibrosis in hamsters and mice (16,17). However, the in vivo selectivity of such drugs for MC chymase remains to be fully defined.…”

Section: Mcpt4 Contributes To Blm-induced Inflammation In the Bronchomentioning

confidence: 99%

“…High levels of histamine have been reported in the bronchoalveolar lavage (BAL) of patients with pulmonary fibrosis (14). Additionally, expression of MC chymase is increased in human lung fibrosis (15), and two inhibitors of MC chymase (NK3201 and SUN C8077) can reduce BLM-induced experimental fibrosis in hamsters and mice (16,17) (recently reviewed in Ref. 18).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Mast Cells Contribute to Bleomycin-Induced Lung Inflammation and Injury in Mice through a Chymase/Mast Cell Protease 4–Dependent Mechanism

Reber

Daubeuf

Pejler

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

Mast cells (MCs) are found in large numbers in lungs of patients with pulmonary fibrosis. However, the functions of MCs in lung fibrosis remain largely unknown. We assessed the role of MCs and MC protease 4 (MCPT4), the mouse counterpart of human MC chymase, in a mouse model of bleomycin (BLM)-induced lung injury. We found that levels of inflammation in the bronchoalveolar lavage and the lung, as well as levels of lung fibrosis, were reduced 7 d after intranasal delivery of BLM MC-deficient KitW-sh/W-sh mice compared with wild-type (WT) mice. Confirming the implication of MCs in these processes, we report that the levels of inflammation and fibrosis observed in KitW-sh/W-sh mice can be restored to those observed in WT mice after the adoptive transfer of bone marrow–derived cultured MCs into KitW-sh/W-sh mice. Additionally, we show that levels of inflammation and fibrosis are also reduced in MC chymase MCPT4-deficient mice as compared with WT mice at day 7, suggesting a role for MC-derived MCPT4 in these processes. Our results support the conclusion that MCs can contribute to the initial lung injury induced by BLM through release of the MCPT4 chymase.

show abstract

Section: Discussionsupporting

confidence: 77%

Section: Mcpt4 Contributes To Blm-induced Inflammation In the Bronchomentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Mast Cells Contribute to Bleomycin-Induced Lung Inflammation and Injury in Mice through a Chymase/Mast Cell Protease 4–Dependent Mechanism

Reber

Daubeuf

Pejler

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…In addition to cytokine production, an increase in the protease activity was measured within the supernatant of silica-exposed BMMC ( Figure 6). The production of mast cell proteases may be another important mechanism in the development of silicosis since mast cell chymase has been reported to be involved in a bleomycininduced model of pulmonary fibrosis by mediating the cleavage of TGF-␤1 to its active form (44). In addition to chymase, mast cell tryptase has been reported to be involved in activation of fibroblasts and stimulation of collagen production (45)(46)(47).…”

Section: W-shmentioning

confidence: 99%

Silica-Directed Mast Cell Activation Is Enhanced by Scavenger Receptors

Brown

Swindle

Kushnir-Sukhov

et al. 2007

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Inhalation of crystalline silica results in pulmonary fibrosis and silicosis. It has been suggested that mast cells play a role in these conditions. How mast cells would influence pathology is unknown. We thus explored mast cell interactions with silica in vitro and in B6.CgKit W-sh mast cell-deficient mice. B6.Cg-Kit W-sh mice did not develop inflammation or significant collagen deposition after instillation of silica, while C57Bl/6 wild-type mice did have these findings. Given this supporting evidence of a role for mast cells in the development of silicosis, we examined the ability of silica to activate mouse bone marrow-derived mast cells (BMMC), including degranulation (␤-hexosaminidase release); production of reactive oxygen species (ROS) and inflammatory mediators; and the effects of silica on Fc⑀RI-dependent activation. Silica did not induce mast cell degranulation. However, TNF-␣, IL-13, monocyte chemotactic protein-1, protease activity, and production of ROS were dose-dependently increased after silica exposure, and production was enhanced after Fc⑀RI stimulation. This mast cell activation was inhibited by anti-inflammatory compounds. As silica mediates some effects in macrophages through scavenger receptors (SRs), we first determined that mast cells express scavenger receptors; then explored the involvement of SR-A and macrophage receptor with colleagenous structure (MARCO). Silica-induced ROS formation, apoptosis, and TNF-␣ production were reduced in BMMC obtained from SR-A, MARCO, and SR-A/MARCO knockout mice. These findings demonstrate that silica directs mast cell production of inflammatory mediators, in part through SRs, providing insight into critical events in the pathogenesis and potential therapeutic targets in silicosis. Keywords: B6.Cg-kitW-sh sash mouse; CD204; macrophage receptor with collagenous structure; mast cell; silicosis; SR-A Among environmental exposures that lead to pathologic changes in tissues is crystalline silica, which can result in occupational silicosis from inhalation of silica dusts in manufacturing, construction, farming, and mining operations. Silicosis, for which there is no effective treatment, leads to decreased pulmonary function and increased susceptibility to diseases of the respiratory tract (1, 2).Involvement of mast cells in silica-induced pulmonary inflammation has been suggested by two clinical observations. First, the number of mast cells within the lungs of individuals exposed to silica dust is increased (3). Second, an increase in mast cells staining for basic fibroblast growth factor located within silicotic nodules has been reported in lung sections obtained from patients with silicosis (4). Despite the suggestive CLINICAL RELEVANCEThis study demonstrates a role for mast cells in silicosis and is the first study to examine direct effects of silica on mast cell biology. It provides evidence that treatment of silicosis should explore mast cells as a potential therapeutic target.evidence for a role of mast cells in the development of silicosis, there are ...

show abstract

“…Inibidores de quimase podem reduzir a fibrose em modelos animais (TAKAI et al, 2003;TOMIMORI et al, 2003;SAKAGUCHI et al, 2004). Ainda se desconhece os mecanismos pelos quais a quimase contribui para fibrose.…”

Section: -Fibroseunclassified

Expressão e caracterização das quimases recombinantes específicas de mastócitos de camundongos (mMCP4 e 5)

Santana¹

View full text Add to dashboard Cite

Involvement of mast cell chymase in bleomycin-induced pulmonary fibrosis in mice

Cited by 51 publications

References 28 publications

Mast Cells Contribute to Bleomycin-Induced Lung Inflammation and Injury in Mice through a Chymase/Mast Cell Protease 4–Dependent Mechanism

Mast Cells Contribute to Bleomycin-Induced Lung Inflammation and Injury in Mice through a Chymase/Mast Cell Protease 4–Dependent Mechanism

Silica-Directed Mast Cell Activation Is Enhanced by Scavenger Receptors

Expressão e caracterização das quimases recombinantes específicas de mastócitos de camundongos (mMCP4 e 5)

Contact Info

Product

Resources

About