Ureaplasma urealyticum induces apoptosis in human lung epithelial cells and macrophages.
Chronic lung disease (CLD) of prematurity remains a significant cause of morbidity among premature infants. It is a multifactorial disorder and characterized by an early increased number of neutrophils and alveolar macrophages, with later architectural epithelial and endothelial cell damage. Recently, apoptosis of type 2 pneumocytes in the lung of preterm neonates with acute and chronic lung disease has been examined and apoptosis of mesenchymal cells was detected in the chronic stage of bronchopulmonary dysplasia. Infection and inflammatory responses in the lungs play important roles. However, the contribution of Ureaplasma urealyticum to the development of CLD is debated. We found that U. urealyticum induced apoptosis in human type II lung epithelial cells (A549 cell line) and macrophages (derived from human monocytic cell line THP-1) by measuring the outer leaflets translocation of phosphatidylserine (flow cytometry analysis and fluorescence microscopy assessment), DNA fragmentation analysis, cell morphology changes such as diminution in cell volume, increased cytoplasmic staining, and nuclear pyknosis (hematoxylin and eosin staining) and viable counting (trypan blue exclusion). Anti-TNF-alpha monoclonal antibody partially protected the macrophages from undergoing apoptosis after infection with U. urealyticum. Our findings imply that U. urealyticum might be involved in impairing lung structure and host immune response during the development of CLD.
Li
Ying-Hua
YH
Neonatal Unit, Astrid Lindgren Children's Hospital, Karolinska Institutet, Stockholm, Sweden. ying-hua.li@kbh.ki.se
Chen
Ming
M
Brauner
Annelie
A
Zheng
Chengyun
C
Skov Jensen
Jørg
J
Tullus
Kjell
K
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002908:Chronic Disease; D053938:DNA Fragmentation; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D008168:Lung / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D008171:Lung Diseases / Q000276:immunology / Q000382:microbiology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D008856:Microscopy, Fluorescence; D010718:Phosphatidylserines / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D016869:Ureaplasma Infections / Q000473:pathology; D016990:Ureaplasma urealyticum / Q000276:immunology / Q000472:pathogenicity*
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D010718:Phosphatidylserines; D014409:Tumor Necrosis Factor-alpha