scholarly journals Particulate Matter Increases the Severity of Bleomycin-Induced Pulmonary Fibrosis through KC-Mediated Neutrophil Chemotaxis

2019 ◽  
Vol 21 (1) ◽  
pp. 227
Author(s):  
I-Yin Cheng ◽  
Chen-Chi Liu ◽  
Jiun-Han Lin ◽  
Tien-Wei Hsu ◽  
Jyuan-Wei Hsu ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Neutrophil Elastase ◽  
Bronchoalveolar Lavage Fluid ◽  
Immune Cell ◽  
Underlying Mechanism ◽  
Lavage Fluid ◽  
Saline Control ◽  
Neutrophil Chemotaxis ◽  
Elastase Level ◽  
Cell Profile

Background: Although particular matter (PM) increases incidence and severity of idiopathic pulmonary fibrosis, the underlying mechanism remains elusive. Methods: The effects of PM were evaluated in a murine model of bleomycin-induced pulmonary fibrosis. Mice were divided into four groups, receiving: (1) Saline (control), (2) bleomycin, (3) PM, or (4) bleomycin plus PM (Bleo+PM). Additional groups of Bleo+PM mice were treated with sivelestat (an inhibitor of neutrophil elastase) or reparixin (a C-X-C motif chemokine receptor 2 antagonist), or were genetically modified with keratinocyte chemoattractant (KC) deletion. Results: Pulmonary fibrosis was not observed in the control or PM groups. Bleomycin induced pulmonary fibrosis within 14 days. The Bleo+PM group showed worse pulmonary fibrosis when compared to the bleomycin group. Analyses of immune cell profile and chemokine/cytokine concentrations at day 2-bronchoalveolar lavage fluid (BALF) revealed that the Bleo+PM group had increased neutrophil number and elastase level and KC concentration compared to the bleomycin group. Neutrophil elastase activated the Smad2/Smad3/α-SMA pathway to induce collagen deposition, while sivelestat abrogated the increased severity of pulmonary fibrosis caused by PM. Chemotaxis assay revealed that BALF of the Bleo+PM group recruited neutrophil, which was dependent on KC. Further, genetic KC deletion or pharmaceutical inhibition of KC binding to CXCR2 with reparixin ameliorated the PM-induced increased severity of pulmonary fibrosis. Conclusions: These data provide evidence that the PM-induced increased severity of pulmonary fibrosis depends on KC-mediated neutrophil chemotaxis and give additional mechanic insight that will aid in the development of therapeutic strategies.

Cytokine profile of bronchoalveolar lavage fluid in patients with combined pulmonary fibrosis and emphysema

Respirology ◽  
2012 ◽  
Vol 17 (5) ◽  
pp. 814-820 ◽  
Author(s):  
SADATOMO TASAKA ◽  
KOSUKE MIZOGUCHI ◽  
YOHEI FUNATSU ◽  
HO NAMKOONG ◽  
WAKAKO YAMASAWA ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Cytokine Profile

Leukotriene B4 induces airway hyperresponsiveness in dogs

1985 ◽  
Vol 59 (6) ◽  
pp. 1941-1946 ◽  
Author(s):  
P. M. O'Byrne ◽  
G. D. Leikauf ◽  
H. Aizawa ◽  
R. A. Bethel ◽  
I. F. Ueki ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Leukotriene B4 ◽  
Airway Responsiveness ◽  
Thromboxane B2 ◽  
Neutrophil Chemotaxis ◽  
Pulmonary Resistance ◽  
Thromboxane Synthase Inhibitor ◽  
Synthase Inhibitor ◽  
Cellular Components

We studied the effect of leukotriene B4 aerosols on airway responsiveness to inhaled acetylcholine aerosols and on the cellular components and cyclooxygenase metabolites in bronchoalveolar lavage fluid in dogs. Inhalation of leukotriene B4 aerosols had no effect on resting total pulmonary resistance but increased airway responsiveness, an effect that was maximum in 3 h and that returned to control levels within 1 wk. Three hours after leukotriene B4, the number of neutrophils and the concentration of thromboxane B2 recovered in lavage fluid increased markedly. Pretreatment with the thromboxane synthase inhibitor OKY-046 prevented the increases in airway responsiveness and in thromboxane B2 but did not alter neutrophil chemotaxis. Thus we speculate that leukotriene B4 causes neutrophil chemotaxis and release of thromboxane B2, which increases airway responsiveness.

scholarly journals The Effects of Lung-Moistening Herbal Medicines on Bleomycin-Induced Pulmonary Fibrosis Mouse Model

Processes ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 102
Author(s):  
Junmo Ahn ◽  
Hyejin Joo ◽  
Jihye Park ◽  
Jae-Woo Park ◽  
Kwan-Il Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pulmonary Fibrosis ◽  
Mouse Model ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Herbal Medicines ◽  
Intratracheal Instillation ◽  
Lavage Fluid ◽  
Septal Thickness ◽  
Different Doses

In traditional medicine, lung-moistening herbal medicines (LMHM) are regarded as a major option for treating symptoms of pulmonary fibrosis (PF) including dry cough and dyspnea. As PF agents are being applied to the development of lung cancer agents, PF and lung cancer are reported to have high pathological and pharmacological relationships. This study was proposed to identify candidates for the treatment of PF via investigating the effect of LMHM on PF mouse model. PF was induced by intratracheal instillation of bleomycin. Six water extracts of LMHM such as Farfarae Flos (FAF), Trichosanthis Semen (TRS), Lilii Bulbus (LIB), Adenophorae Radix (ADR), Asteris Radix (ASR), and Scrophulariae Radix (SCR) were prepared and administered (300 mg/kg) orally for 10 days after induction. The changes in body weight, histopathology, and immune cell of bronchoalveolar lavage fluid (BALF) were investigated. Among those, LIB and ADR significantly decreased the deposition of collagen and septal thickness of alveolar and terminal bronchiole. Moreover, SCR, TRS, LIB, and ADR decreased total cells, macrophages, and lymphocytes in BALF. Taken together, ADR and LIB could be the candidates to reduce PF. Further studies on their effects at different doses and analysis of their underlying molecular mechanisms are needed.

scholarly journals Syndecan-4 Inhibits the Development of Pulmonary Fibrosis by Attenuating TGF-β Signaling

2019 ◽  
Vol 20 (20) ◽  
pp. 4989 ◽  
Author(s):  
Yoshinori Tanino ◽  
Xintao Wang ◽  
Takefumi Nikaido ◽  
Kenichi Misa ◽  
Yuki Sato ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Heparan Sulfate ◽  
Bronchoalveolar Lavage Fluid ◽  
Pulmonary Inflammation ◽  
Lavage Fluid ◽  
Lung Fibroblasts ◽  
Fibrosis Score ◽  
Wild Type ◽  
Deficient Mice

Syndecan-4 is a transmembrane heparan sulfate proteoglycan expressed in a variety of cells, and its heparan sulfate glycosaminoglycan side chains bind to several proteins exhibiting various biological roles. The authors have previously demonstrated syndecan-4′s critical roles in pulmonary inflammation. In the current study, however, its role in pulmonary fibrosis was evaluated. Wild-type and syndecan-4-deficient mice were injected with bleomycin, and several parameters of inflammation and fibrosis were analyzed. The mRNA expression of collagen and α-smooth muscle action (α-SMA) in lung tissues, as well as the histopathological lung fibrosis score and collagen content in lung tissues, were significantly higher in the syndecan-4-deficient mice. However, the total cell count and cell differentiation in bronchoalveolar lavage fluid were equivalent between the wild-type and syndecan-4-deficient mice. Although there was no difference in the TGF-β expression in lung tissues between the wild-type and syndecan-4-deficient mice, significantly more activation of Smad3 in lung tissues was observed in the syndecan-4-deficient mice compared to the wild-type mice. Furthermore, in the in vitro experiments using lung fibroblasts, the co-incubation of syndecan-4 significantly inhibited TGF-β-induced Smad3 activation, collagen and α-SMA upregulation. Moreover, syndecan-4 knock-down by siRNA increased TGF-β-induced Smad3 activation and upregulated collagen and α-SMA expression. These findings showed that syndecan-4 inhibits the development of pulmonary fibrosis, at least in part, through attenuating TGF-β signaling.

C-type natriuretic peptide attenuates bleomycin-induced pulmonary fibrosis in mice

2004 ◽  
Vol 287 (6) ◽  
pp. L1172-L1177 ◽  
Author(s):  
Shinsuke Murakami ◽  
Noritoshi Nagaya ◽  
Takefumi Itoh ◽  
Takafumi Fujii ◽  
Takashi Iwase ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Bronchoalveolar Lavage ◽  
Continuous Infusion ◽  
Natriuretic Peptide ◽  
Bronchoalveolar Lavage Fluid ◽  
Pulmonary Inflammation ◽  
Physiological Role ◽  
Immunohistochemical Analysis ◽  
Lavage Fluid ◽  
Ki 67

C-type natriuretic peptide (CNP) has been shown to play an important role in the regulation of vascular tone and remodeling. However, the physiological role of CNP in the lung remains unknown. Accordingly, we investigated whether CNP infusion attenuates bleomycin (BLM)-induced pulmonary fibrosis in mice. After intratracheal injection of BLM or saline, mice were randomized to receive continuous infusion of CNP or vehicle for 14 days. CNP infusion significantly reduced the total number of cells and the numbers of macrophages, neutrophils, and lymphocytes in bronchoalveolar lavage fluid. Interestingly, CNP markedly reduced bronchoalveolar lavage fluid IL-1β levels. Immunohistochemical analysis demonstrated that CNP significantly inhibited infiltration of macrophages into the alveolar and interstitial regions. CNP infusion significantly attenuated BLM-induced pulmonary fibrosis, as indicated by significant decreases in Ashcroft score and lung hydroxyproline content. CNP markedly decreased the number of Ki-67-positive cells in fibrotic lesions of the lung, suggesting antiproliferative effects of CNP on pulmonary fibrosis. Kaplan-Meier survival curves demonstrated that BLM mice treated with CNP had a significantly higher survival rate than those given vehicle. These results suggest that continuous infusion of CNP attenuates BLM-induced pulmonary fibrosis and improves survival in BLM mice, at least in part by inhibition of pulmonary inflammation and cell proliferation.

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