(Chest. 2000;117:302S-303S.)
© 2000
American College of Chest Physicians
Evidence for Neutrophil Involvement in the Development of Subclinical Emphysema*
Tomoko Betsuyaku, MD;
Masaharu Nishimura, MD;
Kimihiro Takeyabu, MD;
Mishie Tanino, MD;
P. Venge, MD;
S. Xu, PhD and
Yoshikazu Kawakami, MD, FCCP
*
From the First Department of Medicine (Drs. Betsuyaku, Nishimuru, Takeyabu, Tanino, and Kawakami), Hokkaido University School of Medicine, Sapporo, Japan; and the Department of Clinical Chemistry (Drs. Venge and Xu), University Hospital, Uppsala, Sweden.
Correspondence to: Tomoko Betsuyaku, MD, First Department of Medicine, Hokkaido University School of Medicine, Sapporo 060, Japan
 |
Introduction
|
|---|
Abbreviations: HNL = human neutrophil lipocalin; MMP =
matrix metalloproteinase; NE-
1PI = neutrophil elastase-1
proteinase inhibitor complex
Cigarette
smoking is the major cause of pulmonary emphysema, yet only a small
portion of smokers develops clinically apparent emphysema. Using BAL to
compare asymptomatic smokers having emphysema detected by CT scans with
individuals who have a similar smoking history but do not have
emphysema, we have demonstrated that (1) the concentration of
neutrophil elastase-1 proteinase inhibitor complex (NE-1PI) is
significantly elevated in BAL fluid in the subjects with subclinical
emphysema,1 (2) more NE-1PI is released from cultured
alveolar macrophages in the emphysematous smokers, which supports the
idea more neutrophil elastase is taken up by macrophages in those
subjects,2 and (3) the level of elastin-derived peptides in
BAL fluid correlates with the level of NE-1PI, and is significantly
higher in current smokers than former smokers.3 These
studies have implicated neutrophils in early emphysema. To further
evaluate neutrophil involvement in subclinical emphysema, we measured
human neutrophil lipocalin (HNL) and two matrix metalloproteinases
(MMP), gelatinase B (MMP-9) and neutrophil collagenase (MMP-8) in BAL
fluid from 65 community-based older volunteers. The subjects were
classified according to the presence of emphysema by CT scan and
current smoking status. HNL is a recently isolated 24 kDa protein
secreted from secondary granules of activated neutrophils. It is not
present in macrophages. Despite no difference in the number of
neutrophils, the level of HNL was significantly elevated in BAL fluid
from the subjects with subclinical emphysema compared to smokers
without emphysema. MMP-9 and MMP-8 levels were also significantly
higher in the smokers with emphysema than in smokers without emphysema.
The appearance of 130 kDa gelatinolytic activity that was positive for
HNL by immunoblot indicated the presence of HNL/MMP-9 complexes, and
that neutrophil was a significant source of the MMP-9 in the BAL fluid.
The number of alveolar macrophages in BAL fluid did not discriminate
between smokers with and without emphysema. These data provide further
evidence for neutrophil involvement in the early stage of development
of pulmonary emphysema.
|
References
|
|---|
-
Yoshioka, A, Betsuyaku, T, Nishimura, M, et al (1995) Excessive neutrophil elastase in bronchoalveolar lavage fluid in subclinical emphysema. Am J Respir Crit Care Med 152,2127-2132[Abstract]
-
Betsuyaku, T, Yoshioka, A, Nishimura, M, et al (1995) Neutrophil elastase associated with alveolar macrophages from older volunteers. Am J Respir Crit Care Med 151,436-442[Abstract]
-
Betsuyaku, T, Nishimura, M, Yoshioka, A, et al (1996) Elastin-derived peptides and neutrophil elastase in bronchoalveolar lavage fluid. Am J Respir Crit Care Med 154,720-724[Abstract]
TOP
Introduction
References
