• Title/Summary/Keyword: Alveolar cells

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The Effect of Histamine on Polymorphonuclear Leukocyte-induced Pneumocyte Injury in Vitro (다형핵구에 의한 폐포세포 손상에 Histamine이 미치는 영향)

  • Kim, Young-Kyoon;Kwon, Soon-Seog;Kim, Kwan-Hyung;Han, Ki-Don;Moon, Hwa-Sik;Sang, Jeong-Sup;Park, Sung-Hak
    • Tuberculosis and Respiratory Diseases
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    • v.39 no.3
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    • pp.228-235
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    • 1992
  • Background: Although polymorphonuclear leukocytes (PMN) are important in protecting the airways and alveolar surfaces, there is evidence that they can also injure the lung while exercising their defensive role. However it has been unclear whether PMN-induced pneumocyte injury is mediated by their direct cytotoxic effect on target cells or by PMN-derived cytotoxic mediators. On the other hand histamine was known not only to act as an important chemical mediator participated in the pathogenesis of some atotic and allegic disorders, but also to have an inhibitory effect on normal PMN functions. Method: To study the mechanism by which PMN induce pneumocyte injury, we cocultured PMN from four healthy nonsmokers or their PMN-derived supernatants (PMN-SPN) with monolayers of $^{51}Cr$-labeled human A549 pneumocytes and compared PMN-and PMN-SPN-mediated pneumocyte injuries measured by $^{51}Cr$ release assay. We also compared the effects of histamine on each pneumocyte injury. Results: 1) PMN-SPN showed more injurious effect on A549 pneumocytes than that of PMN itself regardless histamine pretreatment of PMN. 2) Pneumocyte injury by PMN with histamine pretreatment was increased or decreased compared with that by PMN without histamine pretreatment, according to histamine concentrations, and PMN stimulating agents and their concentrations. 3) Pneumocyte injury by PMN-SPN with histamine pretreatment tended to be decreased compared with that by PMN-SPN without histamine pretreatment. Conclusion: Our results suggest that PMN-SPN may play more important role in mediating pneumocyte injury than PMN itself and that histamine may partially play a protective role on PMN-induced pneumocyte injury. Alternatively we conclude that the effects of histamine on PMN-induced pneumocyte injury may be affected by microenvironment in vivo.

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The Therapeutic Effect of Angiotensin II Receptor Antagonist in Idiopathic Pulmonary Fibrosis (특발성 폐섬유화증 환자의 치료에서 Angiotensin II Receptor Antagonist의 치료효과)

  • Woo, Duck Soo;Seol, Won Jong;Kyung, Sun Young;Lim, Young Hee;An, Chang Hyeok;Park, Jeong Woong;Jeong, Sung Hwan;Lee, Jae Woong
    • Tuberculosis and Respiratory Diseases
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    • v.55 no.5
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    • pp.478-487
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    • 2003
  • Background : There have been several studies showing that the angiotensin II and angiotensin converting enzyme(ACE) contributes to the apoptosis of alveolar epithelial cells in idiopathic interstitial pneumonia and the activation of fibroblasts during the process of pulmonary fibrosis. These results suggest that the pulmonary fibrosis can be inhibited by the angiotensin II receptor antagonist(AGIIRA). This study was performed to identify the therapeutic effect of AGIIRA in idiopathic pulmonary fibrosis(IPF). Method : Thirteen patients with IPF, who were diagnosed with an open lung biopsy(6 patients) and furfilling the ATS criteria(7 patients) between March 1999 and October 2001 at the Gachon medical center, were enrolled in this study. Of these patients, eight patients were treated with a regimen including AGIIRA(AT group), and five were treated without AGIIRA(NT group). The pulmonary function tests and dyspnea(ATS scale) were measured at diagnosis and 1 year after treatment. All the data was collected to analyze the therapeutic effect of AGIIRA on the patients with IPF. Results : The AT group contained 8 patients(M:F=4:4) and the NT group contained 5 patients(M:F=3:2). There was no significant difference in the serum angiotensin II level between the two groups($202.5{\pm}58.5$ vs $163.7{\pm}47.3pg/ml$, p>0.05). The AT group showed an upward trend in TLC(+3%), FVC(+4%), FEV1(+3%) and DLco(+2%) compared to the NT group(TLC(-14%), FVC(-3%), FEV1(-4%) except for DLco(+5%)). The dyspnea score in the AT group improved significantly but not in the NT group. Conclusion : These results suggest that the angiotensin II receptor antagonist may have an effect on stabilizing IPF.

Radiation Effect on NO, NOS and TGF-$\beta$ Expressions In Rat Lung (쥐의 폐에서 방사선이 Nitric Oxide (NO), Nitric Oxide Synthase (NO) 및 TGF- $\beta$의 발현에 미치는 영향)

  • Oh Young-Taek;Park Kwang-Joo;Kil Hoon-Jong;Ha Mahn Joon;Chun Mison;Kang Seung-Hee;Park Seong-Eun;Chang Sei-Kyung
    • Radiation Oncology Journal
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    • v.18 no.4
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    • pp.321-328
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    • 2000
  • Purpose :NOS2 induce NO Production and NO activate TGF-${\beta}$. The TGF-${\beta}$ is a inhibitor of NOS2. If this negative feedback mechanism operating in radiation pneumonitis model, NOS2 inhibitor may play a role in TGF-${\beta}$ suppression. We planned this study to evaluate the expression patterns of NO, NOS2 and TGF-${\beta}$ in vivo radiation pneumonitis model. Materials and Methods : Sixty sprague-Dawley rat were irradiated 5 Gy or 20 Gy. They were sacrificed 3, 7, 14, 28 and 56 days after irradiation. During sacrifice, we peformed broncho-alveolar lavage (BAL). The BAL fluids were centrifuged and supernatents were used for measure NO and TGF-${\beta}$, and the cells were used for RT-PCR. Results : After 5 Gy of radiation, NO in BAL fluid increased at 28 days in both lung and TGF-${\beta}$ in left lung at 56 days. NO increased in BAL fluid at 28 days in both lung after irradiation and TGF-${\beta}$ in right lung at 28-56 days after 20 Gy of radiation. After 5 Gy of radiation, NOS2 expression was increased in right lung at 14 days, in both lung at 28 days and in left lung at 56 days. TGF-${\beta}$ expression was reduced in both lung at 28 days and increased in left lung at 56 days. Conclusions :The Proposed feedback mechanism of NO, NOS2 and TGF-${\beta}$ was operated in vivo radiation pneumonitis model. At 56 days, however, NOS2 and TGF-${\beta}$ expressed concurrently in left lung after 5 Gy and in both lung after 20 Gy of radiation.

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Long-term Survival Analysis of Bronchioloalveolar Cell Carcinoma (기관세지폐포암의 장기결과분석)

  • Lee Seung Hyun;Kim Yong Hee;Moon Hye Won;Kim Dong Kwan;Kim Jong Wook;Park Seung Il
    • Journal of Chest Surgery
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    • v.39 no.2 s.259
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    • pp.106-110
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    • 2006
  • Background: Bronchioloalveolar carcinoma (BAC) is an uncommon primary malignancy of the lung, and it accounts for $2{\~}14\%$ of all pulmonary malignancies. According to World Health Organization (WHO) categorisation, BAC is a subtype of adenocarcinoma. The current definition of BAC includes the following: malignant neoplasms of the lung that have no evidence of extrathoracic primary adenocarcinoma, an absence of a central bronchogenic source, a peripheral parenchymal location, and neoplastic cells growing along the alveolar septa. Previous reports had demonstrated a better prognosis following surgery for patients affected by BAC than those affected by other type of non-small cell lung cancer (NSCLC). We aim to analyse Asan Medical Center experiences of BAC. Material and Method: Between 1990 and 2002, 31 patients were received operations for BAC. We analyse retrosepectively sex, age, disease location, preoperative clinical stage, postoperative pathologic stage & complications, survival according to medical record. Result: There were 12 men and 19 women, the average age was 61.09$\pm$10.63 ($31{\~}79$) years. Tumor locations were 7 in RUL, 1 in RML, 4 in RLL, 8 in LUL, 11 in LLL. Operations were 28 lobectomies, 2 pneumonectomies. Postoperative pathologic stage were 12 T1N0M0, 15 T2N0M0, 1 T1N1M0, 1 T1N2M0, 1 T2N2M0, 1 T1N0M1. Mortality were 4 cases ($12.9\%$) and there were no early mortality. Cancer free death was 1 cases, other 3 were cancer related deaths. All of them were affected by distal metastasis and received chemotherapy and each metastatic locations were right rib, brain, and both lung field. The average follow up periods were 50.87$\pm$24.77 months. The overall 3, 5-year survival rate among all patients was $97.1\%,\;83.7\%$, stage I patients overall 2, 5year survival rate was $96.3\%$. The overall disease free 1, 2, 5-year survival rate among all patients was $100\%,\;90\%,\;76\%$ and 2, 5-year survival rate in cases of stage I was $96.4\%,\;90.6\%$. 7 cases ($22.58\%$) were chemotherapies, 1 case ($3.22\%$) was radiation therapy, and 2 cases ($6.45\%$) were chemoradiation therapies. Metastatic locations were 3 cases in lung, 1 case in bone, 1 cases in brain. Conclusion: BAC has a favourable survival and low recurrence rate compare with reported other NSCLC after operative resections.

Young Rabbit Model for Pathophysiologic Study of Acute Lung Injury in Early Childhood (유아기 급성폐손상 병태생리 연구를 위한 어린 토끼 실험모델)

  • 권영민;최석철;박종원;김양원;이양행;황윤호;조광현
    • Journal of Chest Surgery
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    • v.36 no.8
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    • pp.545-558
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    • 2003
  • Adult respiratory distress syndrome (ARDS) is of particular interest because of its severity of the associated lung injury and its high mortality. However, the pathophysiologies of ARDS in infant and childhood groups are still not well clarified inspite of many previous investigations. To investigate the time course of pathophysiology of ARDS in infant and childhood groups, this study was designed with experimental endotoxin-induced ARDS model using young rabbits (8 week-old). Material and Method: Rabbits were divided into the control group (n=8) and the endotoxin-treated group (n=32). The endotoxin group was subdivided into 4 groups by the sampling times as 3, 6, 12 and 24 hr-groups (G- $E_{3,6,12,24,}$ each n=8). The experimental ARDS was made by a bolus injection of endotoxin (Escherichia coli serotype 055 : B5, 0.50 mg/kg) via rabbit ear vein. For evaluation of the hematologic and inflammatory markers, and superoxide dismutase (SOD) concentrations, the blood samples were taken from the heart. The bronchoalveolar lavage fluid (BALF) were obtained for analysis of the leukocytes and protein concentration. With biopsy of the lung, histopathologic changes of the lung were also evaluated. Result: In the endotoxin groups, significant leukopenia (owing to pancytopenia) occurred in 3 and 6-hr groups, which was followed by significant leukocytosis (owing to neutrophilia) in the 12 and 24-hr groups (p<0.05). Serum levels of tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-1 $\beta$ (IL-1 $\beta$) in the endotoxin groups were higher than those of control group (p<0.05). Serum levels of superoxide dismutase (SOD) of G- $E_{3}$ and G- $E_{6}$ were higher than those of control group, whereas those of G- $E_{12}$ were lower than those of control groups (p<0.05). Total leukocyte counts and protein con-centrations in BALF were significantly elevated in the endotoxin groups compared to the control group (p < 0.05). The hemorrhagic pattern of BALF showed occurred in the endotoxin groups. The endotoxin groups (in G- $E_{6}$) had severe infiltration of inflammatory cells (lymphocyte and monocyte) in the pulmonary interstitium and parenchyma, migrations of neutrophil and eosinophil into alveolar spaces and interstitial widening, which are the evidences of acute lung injury. In the endotoxin groups, there were significant positive correlations between the BALF findings and the immunologic markers (TNF-$\alpha$, IL-1$\beta$, SOD) (p<0.05). Conclusion: Severe acute lung injury occurred in all the endotoxin-treated rabbits. The pathophysiologic findings were so progressive until 6-hr by time dependant pattern, and then recovered slowly, Variable hematologic, immuno-logic, and pathologic factors were well correlated in the development and progression of endoxin-induced lung injury. The pathophysiologic responses were sensitive and rapid in young rabbit Young rabbit seemed to be a useful experimental animal model for infant and childhood groups.roups.

The Production and Correlation of Silica Induced Proinflammatory Cytokines and TGF-$\beta$ from Monocytes of Balb/C Mice (Balb/C mouse의 폐장대식세포에서 유리규산 자극에 의한 Proinflammatory Cytokine과 TGF-$\beta$의 생성 및 상관관계)

  • Ki, Shin-Young;Kim, Eun-Young;Kim, Mi-Ho;Uh, Soo-Taek;Kim, Yong-Hoon;Park, Choon-Sik;Lee, Hi-Bal
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.4
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    • pp.823-834
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    • 1998
  • Background: Chronic inhalation of silica induces the lung fiborsis. The alveolar macrophages ingest the inhaled silica; they liberate the pro-inflammatory cytokines such as IL-1$\beta$, IL-6, TNF-$\alpha$ and fibrogenic cytokines, TGF-$\beta$ and PDGF. Cytokines liberated from macrophage have pivotal role in pulmonary fibrosis. There is a complex cytokine network toward fibrosis. However, the exact roles and the interaction among the proinflammatory cytokines and TGF-$\beta$, a fibrogenic cytokine, have not been defined, yet. In this study, we investigated silica induced IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ production and the effect of IL-1$\beta$, IL-6, TNF-$\alpha$ on the production of TGF-$\beta$ from lung macrophages of Balb/C mice. Method: We extracted the lung of Balb/C mice and purified monocytes by Percoll gradient method. Macrphages were stimulated by silica ($SiO_2$) in the various concentration for 2, 4, 8, 12, and 24 hours. The supernatants were used for the measurement of protein levels by bioassay, and cells for the levels of mRNA by in situ hybridization. Results: The production of IL-6 was not observed till 4 hours, and reached the peak levels at 8 hours after stimulation of silica. The production of TNF-$\alpha$ increased from 2 hours and reached the peak levels at 4 hours after stimulation of silica. The spontaneous TGF-$\beta$ production reached the peak levels at 24 hours. TNF-$\alpha$ upregulated the silica induced TGF-$\beta$ production. Silica induced TGF-$\beta$ production was blocked by pretreated anti-TNF-$\alpha$ antibody. In situ hybridization revealed the increased positive signals at 4 hours in IL-6, at 4 hours TNF-$\alpha$ and 12 hours in TGF-$\beta$. Conclusion: The results above suggest that silica induced the sequential production of IL-6, 1NF-$\alpha$ and TGF-$\beta$ from macrophages and TNF-$\alpha$ upregultaes the production of TGF-$\beta$ from silica-induced macrophages.

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Proliferative Properties and Cytokine Secretion of Lung Fibroblast Cell Lines of the Patients with Idiopathic Pulmonary Fibrosis (정상인 및 간질성 폐섬유증 환자들의 폐 병변내 섬유모세포주의 증식양상 및 Cytokine분비능에 관한 연구)

  • Kim, Dong-Soon;Paik, Sang-Hoon;Kong, Kyung-Yup;Kim, Dong-Kwan;Park, Seong-Il;Shim, Tae-Sun;Lim, Chae-Man;Lee, Sang-Do;Koh, Youn-Suck;Kim, Woo-Sung;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.1
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    • pp.128-139
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    • 1998
  • Background: It is well known that various cytokines and growth factors secreted mainly from alveolar macrophages do the key role in the pathogenesis of IPF. But recently it has been known that structural cells like fibroblast can also release cytokines. So the phenotypic changes in fibroblasts of IPF may do a role in continuous progression of fibrosis. The aim of this study is to find out whether there is a change in the biologic properties of the lung fibroblasts of IPF. Subjects and Method: The study was done on 13 patients with IPF diagnosed by open or thoracoscopic lung biopsy and 7 control patients who underwent resectional surgery for lung cancer. Lung fibroblast cell lines (FB) were established by explant culture technique from the biopsy or resected specimen Result: Basal proliferation of the fibroblast of IPF(IFB) measured by BrdU uptake tended to be highter than control fibroblast(NFB) (0.212 0.107 vs $0.319{\pm}0.143$, p=0.0922), also there was no significant difference in proliferation after the stimulation with PDGF or 10% serum. On the contrary, the degree of inhibition in proliferation by PGE2 was significantly lower($33.0{\pm}13.1%$) in IFB than control($46.7{\pm}10.0%$, p=0.0429). The IFB secreted significantly higher amount of MCP-l($l574{\pm}1283$ pg/ml) spontaneously than NFB($243{\pm}100$ pg/ml) and also after the stimulation with TGF-$\beta$($3.23{\pm}1.31$ ng/ml vs $0.552{\pm}0.236$ ng/ml, p=0.0012). Similarly IL-8 and IL-6 seretion of IFB was significantly higher than NFB at basal state and with TGF-$beta$ stimulation. But after the maximal stimulation with IL-1,8, no significant difference in cytokine secretion was found between IFB and NFB. Conclusion : Above data suggest that the fibroblasts of IPF were phenotypically changed and these change may do a role in the pathogenesis of IPF.

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The Evaluation of IL-8 in the Serum of Pneumoconiotic patients (진폐증 환자에서의 혈청내 IL-8 농도)

  • Ahn, Hyeong Sook;Kim, Ji Hong;Chang, Hwang Sin;Kim, Kyung Ah;Lim, Young
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.6
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    • pp.945-953
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    • 1996
  • Background : Many acute and chronic lung diseases including pneumoconiosis are characterized by the presence of increased numbers of activated macrophages. These macrophages generate several inflammatory cell chemoattractants, by which neutrophil migrate from vascular compartment to the alveolar space. Recruited neutrophils secrete toxic oxygen radicals or proteolytic enzymes and induce inflammatory response. Continuing inflammatory response results in alteration of the pulmonary structure and irreversible fibrosis. Recently, a polypeptide with specific neutrophil chemotactic activity, interleukin-8(IL-8), has been cloned and isolated from a number of cells including : monocytes, macrophages and fibroblasts. IL-1 and/or TNF-${\alpha}$ preceded for the synthesis of IL-8, and we already observed high level of IL-1 and TNF-${\alpha}$ in the pneumoconioses. So we hypothesized that IL-8 may be a central role in the pathogenesis of pneumoconiosis. In order to evaluate the clinical utility of IL-8 as a biomarker in the early diagnosis of pneumoconiosis, we investigated the increase of IL-8 in the pneumoconiotic patient and the correlation between IL-8 level and progression of pneumoconiosis. Method : We measured IL-8 in the serum of 48 patients with pneumoconiosis and 16 persons without dust exposure history as a control group. Pneumoconiotic cases were divided into 3 groups according to ILO Classification : suspicious group(n=16), small opacity group(n=16) and large opacity group(n=16). IL-8 was measured by a sandwich enzytne immunoassay technique. All data were expressed as the $mean{\pm}standard$ deviation. Results: 1) The mean value of age was higher in the small opacity and large opacity group than comparison group, but smoking history was even. Duration of dust exposure was not different among 3 pneumoconiosis groups. 2) IL-8 level was $70.50{\pm}53.63pg/m{\ell}$ in the suspicious group, $107.50{\pm}45.88pg/m{\ell}$ in the small opacity group, $132.50{\pm}73.47pg/m{\ell}$ in the large opacity group and $17.85{\pm}33.85pg/m{\ell}$ in the comparison group. IL-8 concentration in all pneumoconiosis group was significant higher than that in the comparison group(p<0.001). 3) IL-8 level tended to increase with the progression of pneumoconiosis. Multiple comparison test using Anova/Scheffe analysis showed a significant difference between suspicious group and large opacity group(p<0.05). 4) The level of IL-8 was correlated with the progression of pneumoconiosis(r=0.4199, p<0.05). Conclusion : IL-8 is thought to be a good biomarker for the early diagnosis of pneumoconiosis.

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