A comparative ultrastructural and molecular biological study on Chlamydia psittaci infection in alpha-1 antitrypsin deficiency and non-alpha-1 antitrypsin deficiency emphysema versus lung tissue of patients with hamartochondroma.
BACKGROUND
Chlamydiales are familiar causes of acute and chronic infections in humans and animals. Human pulmonary emphysema is a component of chronic obstructive pulmonary disease (COPD) and a condition in which chronic inflammation manifested as bronchiolitis and intra-alveolar accumulation of macrophages is common. It is generally presumed to be of infectious origin. Previous investigations based on serology and immunohistochemistry indicated Chlamydophila pneumoniae infection in cases of COPD. Furthermore, immunofluorescence with genus-specific antibodies and electron microscopy suggested involvement of chlamydial infection in most cases of pulmonary emphysema, but these findings could not be verified by PCR. Therefore, we examined the possibility of other chlamydial species being present in these patients.


METHODS
Tissue samples from patients having undergone lung volume reduction surgery for advanced alpha-1 antitrypsin deficiency (AATD, n = 6) or non-alpha-1 antitrypsin deficiency emphysema (n = 34) or wedge resection for hamartochondroma (n = 14) were examined by transmission electron microscopy and PCR.


RESULTS
In all cases of AATD and 79.4% of non-AATD, persistent chlamydial infection was detected by ultrastructural examination. Intra-alveolar accumulation of macrophages and acute as well as chronic bronchiolitis were seen in all positive cases. The presence of Chlamydia psittaci was demonstrated by PCR in lung tissue of 66.7% AATD vs. 29.0% non-AATD emphysema patients. Partial DNA sequencing of four positive samples confirmed the identity of the agent as Chlamydophila psittaci. In contrast, Chlamydophila pneumoniae was detected only in one AATD patient. Lung tissue of the control group of non-smokers with hamartochondroma was completely negative for chlamydial bodies by TEM or chlamydial DNA by PCR.


CONCLUSIONS
These data indicate a role of Chlamydophila psittaci in pulmonary emphysema by linking this chronic inflammatory process to a chronic infectious condition. This raises interesting questions on pathogenesis and source of infection.
Theegarten
Dirk
D
Institute of Pathology, Ruhr University Bochum, BG-Kliniken Bergmannsheil, Bürkle-de-la-Camp-Platz 1, D-44789 Bochum, Germany. dirk.theegarten@ruhr-uni-bochum.de.
Anhenn
Olaf
O
Hotzel
Helmut
H
Wagner
Mathias
M
Marra
Alessandro
A
Stamatis
Georgios
G
Mogilevski
Grigori
G
Sachse
Konrad
K
D001483:Base Sequence; D016022:Case-Control Studies; D016993:Chlamydophila pneumoniae / Q000235:genetics / Q000302:isolation & purification / Q000648:ultrastructure; D002691:Chlamydophila psittaci / Q000235:genetics / Q000302:isolation & purification* / Q000648:ultrastructure; D004269:DNA, Bacterial / Q000032:analysis / Q000737:chemistry; D004275:DNA, Ribosomal / Q000737:chemistry; D005260:Female; D006222:Hamartoma / Q000382:microbiology; D006801:Humans; D008168:Lung / Q000382:microbiology* / Q000473:pathology / Q000648:ultrastructure; D008171:Lung Diseases / Q000382:microbiology; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D009956:Psittacosis / Q000150:complications* / Q000382:microbiology; D011656:Pulmonary Emphysema / Q000209:etiology / Q000382:microbiology* / Q000473:pathology; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D012907:Smoking / Q000009:adverse effects; D019896:alpha 1-Antitrypsin Deficiency / Q000150:complications*
D004269:DNA, Bacterial; D004275:DNA, Ribosomal; D012336:RNA, Ribosomal, 16S