Am. J. Respir. Crit. Care Med., Vol 155, No. 4, 04 1997, 1217-1221.
Elevated levels of cytokeratin 19 in the bronchoalveolar lavage fluid of patients with chronic airway inflammatory diseases--a specific marker for bronchial epithelial injury
H Nakamura, S Abe, Y Shibata, H Yuki, H Suzuki, H Saito, M Sata, S Kato and H Tomoike
First Department of Internal Medicine, Yamagata University School of Medicine, Japan.
Cytokeratin 19 (CK19) is a specific cytoskeletal structure of simple
epithelia, including bronchial epithelial cells (BEC). Since CK19 is
released from injured bronchial epithelium, we investigated the levels of
CK19 fragments in the bronchoalveolar lavage fluid (BALF) of eight patients
with chronic airway inflammatory diseases (CAID) using an enzyme-linked
immunosorbent assay (ELISA). Included in our test group were four cases of
chronic bronchitis, three cases of bronchiectasis, and one case of diffuse
panbronchiolitis. There were also 15 control subjects (five asymptomatic
smokers and 10 nonsmokers). BALF from the nonsmokers as well as from the
asymptomatic smokers contained few CK19 fragments (0.2 +/- 0.2 and 1.9 +/-
0.8 pg/ml, respectively). In contrast, significantly high levels of CK19
were present in the BALF of patients with CAID (21.7 +/- 5.7 pg/ml; p <
0.01 versus nonsmoking controls). In addition, CK19 fragment concentrations
in BALF correlated significantly with the number of neutrophils (r = 0.722,
p < 0.01) but not with the numbers of macrophages or lymphocytes in
BALF. BALF from patients with CAID contained high levels of neutrophil
elastase (NE) activity, suggesting that NE might be an important stimulus
for the release of CK19 from BEC. To prove this, we incubated BET-1A cells,
a human immortalized bronchial epithelial cell line, both in the absence
and the presence of inflammatory mediators (including NE, tumor necrosis
factor-alpha [TNF-alpha], and hydrogen peroxide). We then measured the
concentration of CK19 fragments in the culture supernatants with ELISA.
BET-1A cells released CK19 fragments into their culture supernatants after
treatment with NE but not after treatment with TNF or hydrogen peroxide.
Further, we demonstrated that CK19 cleaved by NE could not be detected by
ELISA. Our results suggest that CK19 measurement in BALF is useful for
assessing the presence of bronchial epithelial injuries.
