α1,6-Fucosyltransferase (Fut8) is implicated in vulnerability to elastase-induced emphysema in mice and a possible non-invasive predictive marker for disease progression and exacerbations in chronic obstructive pulmonary disease (COPD).
Fut8 (α1,6-Fucosyltransferase) heterozygous knock-out (Fut8(+/-)) mice had an increased influx of inflammatory cells into the lungs, and this was associated with an up-regulation of matrix metalloproteinases, MMP-2 and MMP-9, after treatment with porcine pancreatic elastase (PPE), exhibiting an emphysema-prone phenotype as compared with wild type mice (Fut8(+/+)). The present data as well as our previous data on cigarette-smoke-induced emphysema [8] led us to hypothesize that reduced Fut8 levels leads to COPD with increased inflammatory response in humans and is associated with disease progression. To test this hypothesis, symptomatic current or ex-smokers with stable COPD or at risk outpatients were recruited. We investigated the association between serum Fut8 activity and disease severity, including the extent of emphysema (percentage of low-attenuation area; LAA%), airflow limitation, and the annual rate of decline in forced expiratory volume in 1 s (FEV(1)). Association with the exacerbation of COPD was also evaluated over a 3-year period. Serum Fut8 and MMP-9 activity were measured. Fut8 activity significantly increased with age among the at risk patients. In the case of COPD patients, however, the association was not clearly observed. A faster annual decline of FEV(1) was significantly associated with lower Fut8 activity. Patients with lower Fut8 activity experienced exacerbations more frequently. These data suggest that reduced Fut8 activity is associated with the progression of COPD and serum Fut8 activity is a non-invasive predictive biomarker candidate for progression and exacerbation of COPD.
Dept. of Internal Medicine, Division of Pulmonary Medicine, Infectious Diseases and Oncology, and Respiratory Care Clinic, Nippon Medical School, Tokyo 102-0074, Japan.
Koichiro
K
Kamio
Takayuki
T
Yoshida
Congxiao
C
Gao
Takeo
T
Ishii
Fumi
F
Ota
Takashi
T
Motegi
Satoshi
S
Kobayashi
Reiko
R
Fujinawa
Kazuaki
K
Ohtsubo
Shinobu
S
Kitazume
Takashi
T
Angata
Arata
A
Azuma
Akihiko
A
Gemma
Masaharu
M
Nishimura
Tomoko
T
Betsuyaku
Kozui
K
Kida
Naoyuki
N
Taniguchi
D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005647:Fucosyltransferases / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010196:Pancreatic Elastase / Q000494:pharmacology; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000201:enzymology / Q000473:pathology*; D011656:Pulmonary Emphysema / Q000097:blood / Q000201:enzymology / Q000473:pathology*
D015415:Biomarkers; D005647:Fucosyltransferases; C020559:Glycoprotein 6-alpha-L-fucosyltransferase; D010196:Pancreatic Elastase; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse