• Tuberculosis and Respiratory Diseases
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• 제65권4호
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• pp.301-307
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• 2008

연구배경: Triggering receptor expressed on myeloid cells-1 (TREM-1)은 호중구와 단핵구의 표면에 표현되는 수용체로 호중구가 자극되면 표면에서 떨어져 수용체인 sTREM-1으로 존재하며 염증반응을 증폭시킨다. 본 연구는 호중구의 활성화가 중요한 병인인 급성호흡곤란증후군 환자의 기관지폐포세척액과 혈청에서 측정한 sTREM-1의 농도가 예후인자로서 유용성이 있는지 확인하고자 시행되었다. 방 법: 32명의 급성호흡곤란증후군 환자가 포함되었고 이 중 15명이 생존군, 17명이 사망군으로 분류되었다. 중증도 지표로 APACHE II score, Clinical Pulmonary Infection Score (CPIS)를 측정하였고, 기관지폐포세척액과 혈청에서 sTREM-1 농도를 측정하였고 중환자실 사망여부를 확인하였다. 결 과: 진단 시 급성호흡곤란증후군 환자의 혈청 내 sTREM-1의 농도는 사망군에서 생존군 보다 유의하게 상승되어 있었으나 ($54.3{\pm}10.3pg/ml$ vs. $22.7{\pm}2.3pg/ml$, p<.05) 기관지폐포세척액 내의 sTREM-1의 농도는 차이가 없었다. 혈청 내 sTREM-1의 농도는 급성호흡곤란증후군 환자의 예후를 예측할 수 있는 독립적인 인자(OR: 22.051, 95% CI: 1.780~273.146, p=0.016)이었고, 33pg/ml 경계로 분류 시 중환자실 사망률을 예측하는데 71%의 민감도와 93%의 특이도를 보였다. 결 론: 급성호흡곤란증후군 환자의 진단 당시 측정한 혈청 sTREM-1의 농도는 중요한 예후 인자로서 유용성이 있을 것으로 생각된다.

• Toxicological Research
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• 제29권2호
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• pp.121-127
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• 2013

Nanotoxicological research has shown toxicity of nanomaterials to be inversely related to particle size. However, the contribution of agglomeration to the toxicity of nanomaterials has not been sufficiently studied, although it is known that agglomeration is associated with increased nanomaterial size. In this study, we prepared aerosols of nano-sized carbon black by 2 different ways to verify the effects of agglomeration on the toxicity and deposition of nano-sized carbon black. The 2 methods of preparation included the carbon black dispersion method that facilitated clustering without sonication and the carbon black dispersion method involving sonication to achieve scattering and deagglomeration. Male Sprague-Dawley rats were exposed to carbon black aerosols 6 hr a day for 3 days or for 2 weeks. The median mass aerodynamic diameter of carbon black aerosols averaged $2.08{\mu}m$ (for aerosol prepared without sonication; group N) and $1.79{\mu}m$ (for aerosol prepared without sonication; group S). The average concentration of carbon black during the exposure period for group N and group S was $13.08{\pm}3.18mg/m^3$ and $13.67{\pm}3.54mg/m^3$, respectively, in the 3-day experiment. The average concentration during the 2-week experiment was $9.83{\pm}3.42mg/m^3$ and $9.08{\pm}4.49mg/m^3$ for group N and group S, respectively. The amount of carbon black deposition in the lungs was significantly higher in group S than in group N in both 3-day and 2-week experiments. The number of total cells, macrophages and polymorphonuclear leukocytes in the bronchoalveolar lavage (BAL) fluid, and the number of total white blood cells and neutrophils in the blood in the 2-week experiment were significantly higher in group S than in normal control. However, differences were not found in the inflammatory cytokine levels (IL-$1{\beta}$, TNF-${\alpha}$, IL-6, etc.) and protein indicators of cell damage (albumin and lactate dehydrogenase) in the BAL fluid of both group N and group S as compared to the normal control. In conclusion, carbon black aerosol generated by sonication possesses smaller nanoparticles that are deposited to a greater extent in the lungs than is aerosol formulated without sonication. Additionally, rats were narrowly more affected when exposed to carbon black aerosol generated by sonication as compared to that produced without sonication.

• 대한예방한의학회지
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• 제6권1호
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• pp.140-155
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• 2002

Background: SBP(桑白皮)is an herbal medicine which has been used in oriental medicine as a traditional therapeutic agent of bronchial asthma. Objective: This study was performed to investigate the effect of SBP on the anti-hypersensitivity and immune response in the murine of type I hypersensitivity induced by the experiment. Materials and Methods: Laboratory rats were primary sensitized with OA(ovalbumin); on day 1, rats of a Control group and Sample group (SBP group) were systemically immunized by subcutaneous injection of 1 mg OA and 300mg of Al(OH)3 in a total volume of 2ml saline. The rats of the sample group were orally administered with an SBP water extract for 14 days after primary immunization. On day 14 after the systemic immunization, rats received local immunization by inhaling 0.9% saline aerosol containing 2%(wt/vol) OA. A day after local immunization, BAL fluid and serum were collected from the rats. Total cell, lymphocyte, CD4+ T cell, CD8+ T cell, CD4+/CD8+ ratio in the BALF, and IgE level in serum were measured and evaluated. Results: SBP showed a suppressive effect on the immune response in the rats. 1. Total cells in the BALF decreased in the SBP treated group in comparision to the control group, but statistic differences were not observed. 2. Total lymphocytes in the BALF were statistically decreased in SBP treated group in comparision to the control group. 3. CD4+ T cells in the BALF were statistically decreased in SBP treated group in comparision to the control group. 4. CD8+ T cells in the BALF were not statistically different in SBP treated group and the control group. 5. The ratio of CD4+/CD8+ in the BALF was statistically decreased in SBP treated group in comparision to the control group. 6. The IgE level in serum decreased in the SBP treated group in comparision to the control group, but statistic differences were not observed.

• 대한한방내과학회지
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• 제30권4호
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• pp.788-798
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• 2009

목적 : 이 연구는 백련초의 천식마우스 모델에 대한 효과를 조사하기 위해 수행하였다. 방법: 폐 세척액의 전체 세포와 호산구 수 그리고 폐조직으로의 면역세포의 침윤은 헤마톡실린과 에오신 염색으로 관찰 하였다. Interleukin (IL)-4의 발현량은 Enzyme-linked immunosorbent assay을 이용하여 측정하였으며, NO는 Griess roagont을 이용하였다. 결과 : 천식 병리현상의 하나인 Ovalbumin(OVA)에 의한 전체 세포와 호산구 수의 증가는 백련초 추출물 (200 mg/kg)을 처리한 군에서 감소하였다 (respectively, p<0.001 and p<0.01). 또한 OVA에 의한 증가된 면역세포의 침투는 백련초 추출물에 의해 감소하였다 (p < 0.01). 호산구의 침윤증상은 interleukin (IL)-4 그리고 5를 포함한 T helper (Th) 2 반응과 관련있기 때문에 폐세척액에서 IL-4의 발현량을 조사하였다. OVA에 증가한 IL-4는 백련초 추출물에 의해 감소하였다 (p < 0.05). 천식이 염증성 질병이기 때문에, lipopolysaccharide (LPS)로 자극한 RAW 264.7 세포에서 nitrite (NO) 생성을 살펴보았다. LPS에 의해 증가한 NO 생성을 백련초 추출물 (50, 100 and 200 mg/ml)에서 감소하였다 (respectively, p < 0.05, p<0.01 and p<0.05). 결론 : 이런 결과들은 백련초가 천식의 호산구 침윤에 저해효과를 가지고 있다고 나타내며, 백련초 추출물의 천식을 포함한 염증성 질환의 치료에 치료후보물질로 제안할 수 있다.

• Journal of Microbiology and Biotechnology
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• 제25권12호
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• pp.2146-2152
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• 2015

Apios americana Medik (hereinafter Apios) has been reported to treat diseases, including cancer, hypertension, obesity, and diabetes. The therapeutic effect of Apios is likely to be associated with its anti-inflammatory activity. This study was conducted to evaluate the protective effects of Apios in animal models of acute lung injury induced by lipopolysaccharide (LPS) or pandemic H1N1 2009 influenza A virus (H1N1). Mice were exposed to LPS or H1N1 for 2-4 days to induce acute lung injury. The treatment groups were administered Apios extracts via oral injection for 8 weeks before LPS treatment or H1N1 infection. To investigate the effects of Apios, we assessed the mice for in vivo effects of Apios on immune cell infiltration and the level of pro-inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid, and histopathological changes in the lung. After induction of acute lung injury, the numbers of neutrophils and total cells were lower in the Apios-treated groups than in the non-Apios-treated LPS and H1N1 groups. The Apios groups tended to have lower levels of tumor necrosis factor-a and interleukin-6 in BAL fluid. In addition, the histopathological changes in the lungs were markedly reduced in the Apios-treated groups. These data suggest that Apios treatment reduces LPS- and H1N1-induced lung inflammation. These protective effects of Apios suggest that it may have therapeutic potential in acute lung injury.

• Clinical and Experimental Pediatrics
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• 제54권9호
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• pp.373-379
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• 2011

Purpose: 4-1BB (CD 137) is a costimulatory molecule expressed on activated T-cells. Repression by 4-1BB is thought to attenuate Th2-mediated allergic reactions. The aim of this study was to investigate the effect of 4-1BB on allergic airway inflammation in a murine asthma model. Methods: BALB/c mice were sensitized to and challenged with ovalbumin (OVA). Hu.4-1BB-Fc was administered 1 day before the first OVA sensitization or 1 day after the second OVA sensitization. Following antigen challenge, airway responsiveness to methacholine was assessed and bronchoalveolar lavage (BAL) fluid was analyzed. Total immunoglobulin (Ig) E, OVA-specific IgE, $IgG_1$, and $IgG_{2a}$ levels in sera were measured by enzyme-linked immunosorbent assay. Lung pathology was also evaluated. Results: In mice treated with Hu.4-1BB-Fc before the first OVA sensitization, there was a marked decrease in airway hyperresponsiveness, total cell count, and eosinophil count in the BAL fluid. In addition, Hu.4-1BB-Fc treatment decreased serum OVA-specific $IgG_1$ levels and increased serum $IgG_{2a}$ level significantly compared with the corresponding levels in mice sensitized to and challenged with OVA. Hu.4-1BB-Fc-treated mice also showed suppressed peribronchial and perivascular inflammatory cell infiltration. In contrast, treatment with Hu.4-1BB-Fc 1 day after sensitization had no effect on airway hyperresponsiveness and showed less suppression of inflammation in lung tissue. Conclusion: Administration of Hu.4-1BB-Fc can attenuate airway inflammation and hyperreactivity in a mouse model of allergic airway inflammation. In addition, administration before sensitization may be more effective. These findings suggest that 4-1BB may be a useful therapeutic molecule against asthma.

• Tuberculosis and Respiratory Diseases
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• 제62권2호
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• pp.105-112
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• 2007

연구배경: 내독소로 유발된 급성폐손상의 발생기 전에 산화스트레스가 중요한 역할은 한다. 본 실험은 LPS로 유발한 급성폐손상 모델에서 항산화제인 ${\alpha}$-lipoic acid의 치료효과를 보고하였다. 방 법: Sprague-Dawley 쥐를 대상으로 LPS(E.coli, 3mg/Kg)를 기도내 주입 후 ${\alpha}$-lipoic acid를 복강 내 주입하였다. 2시간, 6시간 후에 폐포세척액에서 호중구수, CINC, 시토카인의 농도를 구하고 폐조직에서 MPO를 측정하였다. 결 과: ${\alpha}$-lipoic acid를 후처치한 군에서 LPS 단독군보다 2시간 뒤와 6시간 뒤에 총 세포수와 호중구의 수가 감소하였으나 단백질 농도는 차이가 없었다. 또한 염증성 인자인 TNF-${\alpha}$, IL-$1{\beta}$, IL-6의 농도도 ${\alpha}$-lipoic acid 처치군에서 유의한 감소를 보이지 못하였다. 결 론: LPS 로 급성폐손상 유도 모델에서 ${\alpha}$-lipoic acid의 후처치는 폐장내로의 호중구의 침윤은 억제할 수 있지만 급성폐손상을 약화시키지는 못 하였다.

• IMMUNE NETWORK
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• 제21권2호
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• pp.14.1-14.17
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• 2021

Scrub typhus develops after the individual is bitten by a trombiculid mite infected with Orientia tsutsugamushi. Since it has been reported that pneumonia is frequently observed in patients with scrub typhus, we investigated whether intranasal (i.n.) vaccination with the outer membrane protein of O. tsutsugamushi (OMPOT) would induce a protective immunity against O. tsutsugamushi infection. It was particular interest that when mice were infected with O. tsutsugamushi, the bacteria disseminated into the lungs, causing pneumonia. The i.n. vaccination with OMPOT induced IgG responses in serum and bronchoalveolar lavage (BAL) fluid. The anti-O. tsutsugamushi IgA Abs in BAL fluid after the vaccination showed a high correlation of the protection against O. tsutsugamushi. The vaccination induced strong Ag-specific Th1 and Th17 responses in the both spleen and lungs. In conclusion, the current study demonstrated that i.n. vaccination with OMPOT elicited protective immunity against scrub typhus in mouse with O. tsutsugamushi infection causing subsequent pneumonia.

• Toxicological Research
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• 제26권3호
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• pp.217-222
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• 2010

Many studies have reported that bleomycin, anti-cancer drug, induces pulmonary fibrosis as a side effect. However, few investigations have focused on the dose-response effects of bleomycin on pulmonary fibrosis. Therefore, in the present study, we investigated the effects of different doses of bleomycin in male mice. ICR mice were given 3 consecutive doses of bleomycin: 1, 2, or 4 mg/kg in bleomycin-treated (BT) groups and saline only in vehicle control (VC) groups. The animals were sacrificed at 7 and 24 days postinstillation. The severity of pulmonary fibrosis was evaluated according to inflammatory cell count and lactate dehydrogenase (LDH) activity in the broncho alveolar lavage fluid (BALF), and lung tissues were histologically evaluated after hematoxylin and eosin (H&E), and Masson's trichrome staining. BT groups exhibited changed cellular profiles in BAL fluid compared to the VC group, which had an increased number of total cells, neutrophils, and lymphocytes and a modest increase in the number of macrophages at 7 days post-bleomycin instillation. Moreover, BT groups showed a dose-dependent increase in LDH levels and inflammatory cell counts. However, at 24 days after treatment, collagen deposition, interstitial thickening, and granulomatous lesions were observed in the alveolar spaces in addition to a decrease in inflammatory cells. These results indicate that pulmonary fibrosis induced by 4 mg/kg bleomycin was more severe than that induced by 1 or 2 mg/kg. These data will be utilized in experimental animal models and as basic data to evaluate therapeutic candidates through non-invasive monitoring using the pulmonary fibrosis mouse model established in this study.

• Journal of Radiation Protection and Research
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• 제42권4호
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• pp.177-188
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• 2017

Background: Radiation-induced pneumonitis and pulmonary fibrosis are common dose-limiting complications in patients receiving radiotherapy for lung, breast, and lymphoid cancers. In this study, we investigated the characteristics of effective immune cells related to pneumonitis and fibrosis after irradiation. Materials and Methods: After anesthesia, the whole thorax of C57BL/6 mice was irradiated at 14 Gy. The lung tissue and bronchoalveolar lavage fluid were collected at defined time points post-irradiation for the determination of histological and immunohistochemical analysis and inflammatory cell population infiltrated into the lung. Results and Discussion: Whole thoracic irradiation increased the deposition of extracellular matrix (ECM), lung weight, and pleural effusions, which started to die from 4 months later. At 4 months after irradiation, the numbers of macrophages and lymphocytes as well as neutrophils were increased dramatically in the lung. Interestingly, the macrophages that were recruited into the lung after irradiation had an enlarged foamy morphology. In addition, the expressions of chemokines (CCL-2, CCL-3, CXCL-10) for the attraction of macrophages and T cells were higher in the lung of irradiated mice. The high expressions of these chemokines were sustained up to 6 months following irradiation. In thoracic irradiated mice, infiltrated macrophages into the lung had the high levels of Mac-3 antigens on their surface and upregulated the hallmarks of alternatively activated macrophages such as arginase-1 and CD206. Furthermore, the levels of IL-4 and IL-13 were higher in a BAL fluid of irradiated mice. Conclusion: All results show that thoracic irradiation induces to infiltrate various inflammation-related immune cells, especially alternatively activated macrophages, through enhancing the expression of chemokines, suggesting that alternatively activated macrophages are most likely important for leading to pulmonary fibrosis.