权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

A STUDY OF TYPE II ALVEOLAR EPITHELIAL CELLS AS INFECTION SITE OF ACID-FAST BACILLI

Ⅱ型肺泡上皮细胞作为抗酸杆菌感染部位的研究

基本信息

批准号：
10670545
负责人：
SATO Katsumasa
金额：
$ 1.54万
依托单位：
SHIMANE MEDICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670545/
关键词：
ACID-FAST BACIL II MYCOBACTERIUM TUBERCULOSIS MYCOBACTERIUM AVIUM COMPLEX TYPE II ALVEOLAR EPITHELIAL CELLS MACROPHAGES A-549 CELLS INVASION CYTOKINES Mycobacterium avium complex A-549 細胞抗菌剤

项目摘要

1. Antimicrobial effects of clarithromycin (CAM), KRM-1648 (KRM) and levofloxacin (LVFX) against Mycobacterium tuberculosis (MTB) or M.avium complex (MAC) residing in the A-549 human type II alveolar epithelial cells (A-549 cells) were less than the effects of the same drugs against the same organisms residing in Mono Mac 6 human macrophage-like cells (MM6-MΦ).2. Antimicrobial activities of these drugs against MTB and MAC adapted to an intramacrophagic environment (intracellularly adapted : I-type) and those passaged in the 7H9 liquid medium (extracellularly adapted : E-type) were studied. The antibacterial effect of CAM or LVFX against E-type MTB or MAC residing in MM6-MΦs or A-549 cells was stronerg than a case against I-type MTB or MAC within the same cells. On the other hand, the antibacterial effect of KRM for E-type MTB or MAC residing in both cells was weaker than a case for I-type organisms within the same cells.3. Mice were infected intratracheally with MTB or MAC, and the lung sections of the infected mice were observed with transmission electron photomicrographs. The infected bacteria were recognized in type II alveolar epithelial cells in addition to mature granulocytes and macrophages.4. Using a dual chamber system, we examined whether the humoral factor of the A-549 cells infected with MTB or MAC which were released, influenced the anti-MTB or the anti-MAC antibacterial activity of MM6-MΦs. The number of the MTB or MAC organisms residing in MM6-MΦs of the top-chamber was decreased by the existence of A-549 cells infected with the MTB or MAC.5. It was found that the humoral factor (s) that decreased the number of these bacteria might be TNF-α and/or GM-CSF with RT-PCR examination.

1. 克拉霉素（CAM）、KRM-1648 （KRM）和左氧氟沙星（LVFX）对存在于A-549人II型肺泡上皮细胞（A-549细胞）中的结核分枝杆菌（MTB）或M.avium复合物（MAC）的抗菌作用小于相同药物对存在于Mono MAC 6人巨噬细胞样细胞中的相同生物的抗菌作用（MM6-MΦ）。研究了这些药物对巨噬细胞内适应型（细胞内适应型）和7H9液体培养基中传代型（细胞外适应型）的MTB和MAC的抗菌活性。CAM或LVFX对寄生在MM6-MΦs或a -549细胞中的e型MTB或MAC的抑菌作用强于对同一细胞中的i型MTB或MAC的抑菌作用。另一方面，KRM对同时存在于两种细胞中的e型结核分枝杆菌或MAC的抑菌作用弱于同一细胞中的i型结核分枝杆菌。小鼠气管内感染MTB或MAC，用透射电镜观察感染小鼠的肺切片。除了成熟的粒细胞和巨噬细胞外，II型肺泡上皮细胞也可识别感染细菌。采用双室系统，研究了释放的感染MTB或MAC的a -549细胞的体液因子是否影响MM6-MΦs抗MTB或抗MAC的抗菌活性。由于存在感染MTB或MAC的A-549细胞，居住在顶室MM6-MΦs中的MTB或MAC生物的数量减少。通过RT-PCR检测发现，减少这些细菌数量的体液因子可能是TNF-α和/或GM-CSF。