• Journal of Chest Surgery
• /
• 제36권12호
• /
• pp.894-903
• /
• 2003

체내에서 발생하는 산화 질소는 허혈-재관류에 따른 폐혈관 저항을 감소시키고 혈관의 미세 투과도를 줄이고 세포손상을 방지하여 이식 후 폐장 기능의 보전에 도움이 된다고 알려져 있으나, 산화질소 자체의 세포독성으로 인해 재관류 동안 폐 부종을 오히려 증가시킬 수도 있다고 한다. 저자들은 산화 질소의 공여물질인 nitroglycerin을 투여한 분리 폐장 관류 모델을 이용하여 폐장 보존에 이점과 단점을 동시에 가지고 있는 산화질소가 허혈-재관류 과정에서 폐장의 기능에 미치는 영향을 알아보기 위하여 본 연구를 시행하였다. 대상 및 방법: Sprague-Dawley종의 수컷 흰쥐 35마리를 사용하였다. Nitroglycerin (NTG)군(n=18)은 NTG를 정맥 주사하고 University of Wisconsin용액에 혼합하여 폐장 관류를 시행하였고, 대조군(n=17)은 NTG 대신 같은 양의 생리 식염수를 사용하였다. 구득한 심폐블록을 1$0^{\circ}C$에서 24시간 동안 보관한 후, 분리 폐장 관류 모델에서 인체 혈액을 Krebs-Hensleit용액으로 희석하여 60분간 재관류하였다. 재관류하는 동안 기도내압과 페동맥압을 지속적으로 측정하였고, 관류후 30분과 60분에 혈액 내 산소와 이산화탄소 분압을 측정하였다. 재관류가 끝난 후 기관지폐포세척을 통해 폐포 내 단백함량을 측정하였으며, 중성구 침착 정도를 알기 위해 myeloperoxidase (MPO) 활성도를 측정하였다. 걸과: 두 군 간의 기도내압과 폐동맥압은 통계적으로 유의한 차이는 없었으나, NTG군에서 관류기간 중 폐동맥압이 상대적으로 낮게 유지되는 경향이 있었다. 이산화탄소 분압, 기관지폐포세척액 내의 단백질 함량, MPO의 활성도는 두 군에서 유의한 차이는 없었으나, 산소 분압은 NTG 군에서 통계적으로 유의하게 높게 나타났다(p<0.05). 전자현미경 검사에도 대조군에 비해 NTG군에서 폐포구조, 폐포상피세포, 모세혈관배열 등 미세구조의 손상이 적게 나타났다. 결론. 폐장 구득전 NTG의 투여는 폐장의 기능과 미세구조의 유지에 도움이 된다고 판단되며, 임상 폐이식에도 적용이 가능하리라 생각된다.

• The Korean Journal of Physiology and Pharmacology
• /
• 제3권4호
• /
• pp.405-414
• /
• 1999

The role of platelet-activating factor (PAF) was investigated in intestinal ischemia/reperfusion (I/R) induced acute lung injury associated with oxidative stress. To induce acute lung injury following intestinal I/R, superior mesenteric arteries were clamped with bulldog clamp for 60 min prior to the 120 min reperfusion in Sprague-Dawley rats. Acute lung injury by intestinal I/R was confirmed by the measurement of lung leak index and protein content in bronchoalveolar lavage (BAL) fluid. Lung leak and protein content in BAL fluid were increased after intestinal I/R, but decreased by WEB 2086, the PAF receptor antagonist. Furthermore, the pulmonary accumulation of neutrophils was evaluated by the measurement of lung myeloperoxidase (MPO) activity and the number of neutrophils in the BAL fluid. Lung MPO activity and the number of neutrophils were increased (p＜0.001) by intestinal I/R and decreased by WEB 2086 significantly. To confirm the oxidative stress induced by neutrophilic respiratory burst, gamma glutamyl transferase (GGT) activity was measured. Lung GGT activity was significantly elevated after intestinal I/R (p<0.001) but decreased to the control level by WEB 2086. On the basis of these experimental results, phospholipase $A_2\;(PLA_2),$ lysoPAF acetyltransferase activity and PAF contents were measured to verify whether PAF is the causative humoral factor to cause neutrophilic chemotaxis and oxidative stress in the lung following intestinal I/R. Intestinal I/R greatly elevated $PLA_2$ activity in the lung as well as intestine (p<0.001), whereas WEB 2086 decreased $PLA_2$ activity significantly (p<0.001) in both organs. LysoPAF acetyltransferase activity, the PAF remodelling enzyme, in the lung and intestine was increased significantly (p<0.05) also by intestinal I/R. Accordingly, the productions of PAF in the lung and intestine were increased (p<0.001) after intestinal I/R compared with sham rats. The level of PAF in plasma was also increased (p<0.05) following intestinal I/R. In cytochemical electron microscopy, the generation of hydrogen peroxide was increased after intestinal I/R in the lung and intestine, but decreased by treatment of WEB 2086 in the lung as well as intestine. Collectively, these experimental results indicate that PAF is the humoral mediator to cause acute inflammatory lung injury induced by intestinal I/R.

• The Korean Journal of Physiology and Pharmacology
• /
• 제4권3호
• /
• pp.219-226
• /
• 2000

In order to elucidate the role of platelet activating factor (PAF) in the acute lung injury induced by endotoxin (ETX), activities of phospholipase A2, lyso PAF acetyltransferase and oxidative stress by neutrophilic respiratory burst were probed in the present study. To induce acute lung injury, $100\;{\mu}g$ of E.coli ETX (type 0127; B8) was instilled directly into the tracheae of Sprague-Dawley rats. Five hours after the ETX instillation, induction of acute lung injury was confirmed by lung leak index and protein contents in the bronchoalveolar lavage (BAL) fluid. At the same time, lung phospholipase A2 (PLA2) activity and expression of group I and II secretory type PLA2 were examined. In these acutely injured rats, ketotifen fumarate, known as lyso PAF acetyltransferase inhibitor and mepacrine were administered to examine the role of PAF in the pathogenesis of the acute lung injury. To know the effect of the ETX in the synthesis of the PAF in the lungs, lyso PAF acetyltransferase activity and PAF content in the lungs were measured after treatments of ETX, ketotifen fumarate and mepacrine. In addition, the role of neutrophils causing the oxidative stress after ETX was examined by measuring lung myeloperoxidase (MPO) and enumerating neutrophils in the BAL fluid. To confirm the oxidative stress in the lungs, pulmonary contents of malondialdehyde (MDA) were measured. After instillation of the ETX in the lungs, lung leak index increased dramatically (p＜0.001), whereas mepacrine and ketotifen decreased the lung leak index significantly (p＜0.001). Lung PLA2 activity also increased (p＜0.001) after ETX treatment compared with control, which was reversed by mepacrine and ketotifen (p＜0.001). In the examination of expression of group I and II secretory PLA2, mRNA synthesis of the group II PLA2 was enhanced by ETX treatment, whereas ketotifen and WEB 2086, the PAF receptor antagonist, decreased the expression. The activity of the lysoPAF acetyltransferase increased (p＜0.001) after treatment of ETX, which implies the increased synthesis of PAF by the remodelling of lysoPAF in the lungs. Consequently, the contents of the PAF in the lungs were increased by ETX compared with control (p＜0.001), while mepacrine (p＜0.001) and ketotifen (p＜0.01) decreased the synthesis of the PAF in the lungs of ETX treated rats. The infiltration of the neutrophils was confirmed by measuring and enumerating lung MPO and the neutrophils in the BAL fluid respectively. Compared with control, ETX increased lung MPO and number of neutrophils in BAL significantly (p＜0.001) whereas mepacrine and ketotifen decrerased number of neutrophils (p＜0.001) and MPO (p＜0.05, p＜0.001, respectively). The lung MDA contents were also increased (p＜0.001) by ETX treatment, but treatment with mepacrine (p＜0.001) and ketotifen (p＜0.01) decreased the lung MDA contents. Collectively, we conclude that ETX increases PLA2 activity, and that the subsequently increased production of PAF was ensued by the remodelling of the lyso PAF resulting in tissue injury by means of oxidative stress in the lungs.

• Tuberculosis and Respiratory Diseases
• /
• 제38권2호
• /
• pp.143-154
• /
• 1991

Pneumconiosis is a sort of pulmonary fibrosis consequent to the inhalation of the respirable dusts. Thus, the pathogenesis of silicosis have concentrated largely on the early response of alveolar macrophage and the later fibroblastic stimulation. But the role of the other cells and continuing cell injury in the pathogenesis has not been fully studied. And the chemical factors such as prostaglandin, fibroblast stimulating factor and inhibiting factor and chemotaxin are also participated in the mechanism of pulmonary fibrosis in silicosis. In order to clarify the role of alveolar cells and prostaglandin, we investigated the changes of the cellularities in bronchoalveolar lavage fluid and tissue pathology in the experimental silicosis with the time sequence. The experimental animals were divided into 3 groups; control group received only intratracheal injection of 0.5 ml saline, silica group received the intratracheal instillation of 40 mg silica with the same amount saline, and aspirin group received 450 mg/kg of aspirin after silica instillation. The results were as follows: 1) The total cells of bronchoalveolar lavage fluid in the silica group markedly increased in comparison with the control group, but there was no significant difference between the silica and aspirin groups. 2) The percentages of alveolar macrophages to the total number of cells in the silica group tended to be lower than those in the control group and also lower than those in the aspirin group at the 1st week after silica instillation. 3) The percentages of neutrophils to the total number of cells in the silica group were significantly higher than those in the control group during the entire period and also higher than those in the aspirin group at the 3rd day after silica instillation. 4) In the silica group, the percentages of lymphocytes to the total number of cells were increased 143 progressively with the time course and those were significantly higher than those in the control group from the 3rd week after silica administration. There were marked differences of lymphocyte percentages between the silica and aspirin groups at the 1st week after silica instillation. 5) The inflammatory change was observed in the rat lung at the 1st day after silica instillation. Also the silicotic nodule appeared in the silica group at the 1st week but we could not find out that nodule in the aspirin group at that time. The fibrotic changes in the rat lung tended to be increased progressively with the time course, therefore, the diffuse fibrotic pattern appeared in the whole field at the 20th week after silica instillation. 6) By the electron microscopy, there were gradual increases of phagosomes and vacuoles in the alveolar macrophage in the silica group as compared with the control group. These results suggest that the neutrophils and the lymphocytes have also participated in the pulmonary fibrosis even though the alveolar macrophage has a major role, and prostaglandin mediate the inflammation and pulmanary fibrosis in the experimental silicosis.

• Tuberculosis and Respiratory Diseases
• /
• 제52권4호
• /
• pp.419-424
• /
• 2002

경금속 진폐증에 속하는 거대세포 간질성 폐렴은 경금속을 사용한 절삭, 연마의 과정 중 발생하는 분진을 흡입하여 발생하는 것으로 알려져 있으나 이러한 직업력이 불분명한 증례를 개흉생검술을 통해 진단하였기에 보고하는 바이다.

• Tuberculosis and Respiratory Diseases
• /
• 제68권4호
• /
• pp.236-239
• /
• 2010

Hot tub lung is a lung disorder associated with exposure to hot tub water contaminated with Mycobacterium avium complex (MAC). Although its pathogenesis remains unclear, it may be considered hypersensitivity pneumonitis (HP) rather than an infectious disease. We report a case which fulfilled the current diagnostic criteria of hot tub lung. A patient had worked as a cleaner in the public bath for approximately one year and presented with dyspnea for over one month. The computed tomographic finding of bilateral ground glass attenuation and pathologic finding of granulomatous inflammation were consistent with HP. MAC was isolated from bronchoalveolar lavage fluid and hot tub water. After corticosteroid treatment without antimycobacterial medication, the patient improved and there has been no recurrence. The patient has since discontinued working in the public bath.

• Tuberculosis and Respiratory Diseases
• /
• 제68권4호
• /
• pp.226-230
• /
• 2010

Androgen deprivation therapy, which is the standard treatment for metastatic prostate cancer, includes nonsteroidal antiandrogenic drugs, such as flutamide, nilutamide and bicalutamide. Of them, bicalutamide rarely induces interstitial pneumonia. We report a case of bicalutamide-induced interstitial pneumonia. A 68-year old male diagnosed with prostate cancer and multiple bone metastases presented with dry cough and low grade fever for 3 days. He had taken bicalutamide (50 mg/day) for 13 months. High resolution computed tomography revealed ground glass opacity in his right upper lung. The laboratory studies showed no eosinophilia in the serum and bronchoalveolar lavage fluid. Despite the use of antimicrobial agents for 2 weeks, the extent of the lung lesions increased to the left upper and right lower lung. He had no environmental exposure, collagen vascular disease and microbiological causes. Under the suspicion of bicalutamide-induced interstitial pneumonia, bicalutamide was stopped and prednisolone (1 mg/kg/ day) was initiated. The symptoms and radiologic abnormalities were resolved with residual minimal fibrosis.

• Archives of Pharmacal Research
• /
• 제29권4호
• /
• pp.302-309
• /
• 2006

Lupus-like syndrome is characterized by multiple organ injuries including lungs and kidneys. Endotoxin induces a transiently intent systemic inflammatory response and indirectly transient acute lung injury in normal condition. However, whether endotoxin may trigger the persistent development of lung injury in chronic, inflammatory lupus-like syndrome compared with normal condition remains unclear. We examined the pulmonary vascular permeability and production of proinflammatory cytokines, such as TNF-${\alpha}$, IL-6, IL-10 and IFN-${\gamma}$, which play prominent roles in the pathogenesis of lupus-like tissue injury, 6 hand 72 h after i.p. lipopolysaccharide (LPS; endotoxin) injection in pristane-primed chronic inflammation ICR mice characterized by a lupus-like syndrome. These results demonstrated that levels of serum IL-6, IL-10 and IFN-${\gamma}$ and bronchoalveolar lavage (BAL) IL-6 and IFN-${\gamma}$ were remarkably increased 6 h in LPS-exposed pristane-primed mice compared with pristane-primed controls, while pulmonary vascular permeability and levels of serum and BAL TNF-${\alpha}$ were not. And levels of BAL TNF-${\alpha}$, IL-6 and IL-10 were significantly enhanced 72 h in LPS-exposed pristane-primed mice compared with pristane-primed controls. Also, LPS significantly induced the increased in vitro production of TNF-${\alpha}$, IL-6 and IL-10 by lung cells obtained from LPS-exposed pristane-primed mice compared with LPS-exposed normal mice. Our findings indicate that LPS may trigger persistent progression of lung injury through late overproduction of BAL TNF-${\alpha}$, IL-6, and IL-10 in lupuslike chronic inflammation syndrome compared with normal condition.

• 동의생리병리학회지
• /
• 제38권1호
• /
• pp.16-21
• /
• 2024

Haepyoijin-tang and its main components have been used for phlegm, cough and dyspnea. Using a respiratory inflammation model, we intend to reveal the anti-inflammatory effect and pharmacological mechanism of Haepyoijin-tang. We induced the respiratory inflammation model by Aspergillus oryzae protease and ovalbumin administration. Female Balb/c mice (8 weeks old) were classified into four groups as follows: saline control group, aspergillus oryzae protease and ovalbumin induced respiratory inflammation group (vehicle), inflammation with Haepyoijin-tang (200 mg/kg) administration group, inflammation with dexamethasone (5 mg/kg) administration group (n=7). To identify the anti-inflammatory effects of Haepyoijin-tang water extracts, we measured the inflammatory cell number in bronchoalveolar lavage fluid (BALF) and total live lung cell number. In addition, we checked eosinophil ratio and number in BALF. And Interleukin (IL)-5 level was also measured in lung cell culture supernatant. To confirm the mechanism of anti-inflammatory effects, we analyzed the activated helper T cell (CD4⁺CD25⁺ cell) and Th2 cell (CD4⁺GATA3⁺ cell) ratio and number in lung by using flow cytometry. Finally, we attempted to confirm the immune mechanism by measuring the ratio and number of regulatory T cells (CD4⁺Foxp3⁺ cell). Haepyoijin-tang extracts treatment diminished inflammatory cell, especially, eosinophil number in BALF and total live lung cell number. Moreover, IL-5 level was reduced in Haepyoijin-tang treated group. Surprisingly, Haepyoijin-tang extracts administration not only decreased the activated helper T cell but also Th2 cell population in lung. Additionally, regulatory T cell population was increased in Haepyoijin-tang administration group. Our findings proved that Haepyoijin-tang extract have anti-inflammatory efficacy by suppressing Th2 cell activation and promoting regulatory T cell population.

• 대한영상의학회지
• /
• 제84권1호
• /
• pp.298-303
• /
• 2023

전자담배 관련 폐 손상(electronic cigarette or vaping-associated lung injury)은 전자담배에 의해 발생하는 폐 손상으로, 주된 병리 소견은 기질화폐렴 혹은 미만성폐포손상이며 드물게 급성호산구폐렴을 보인다. 본 증례에서 대마 추출물이 없는 니코틴 액상 전자담배 흡연력의 34세 남자 환자가 급성 호흡기 증상, 흉부 CT에서 양측 폐하엽의 주변부의 다발성 경화와 간유리음영, 미만성의 소엽간격막 비후, 흉막삼출을 보였다. 기관지폐포세척액에서는 호산구증이 있었고 감염성 검사들은 모두 음성으로 보였기에 진단기준에 부합하는 급성호산구 폐렴으로 발현한 대마 추출물이 없는 니코틴 액상 전자담배 관련 폐 손상의 희귀한 증례를 보고한다.