(Chest. 2000;117:282S.)
© 2000
American College of Chest Physicians
Proteases and Chemotactic Factors in BAL Fluid From Subjects With Subclinical Emphysema*
Masaharu Nishimura, MD;
Tomoko Betsuyaku, MD;
Mishie Tanino, MD;
Kimihiro Takeyabu, MD;
Kenji Miyamoto, MD and
Yoshikazu Kawakami, MD, FCCP
*
From the First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Correspondence to: Masaharu Nishimura, MD, First Department of Medicine, Hokkaido University School of Medicine, West 7, North 15, Sapporo, 060-8638 Japan
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Introduction
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Abbreviations: IL = interleukin; NE-
1
PI = neutrophil elastase-1 protease inhibitor complex
It is
generally accepted that proteases released from neutrophils and/or
macrophages are involved in the development of emphysema associated
with cigarette smoking. However, it has not been resolved which of
these inflammatory cells is the main source of proteases responsible
for lung destruction. To address this issue, we compared the
concentrations of neutrophil elastase-1 protease inhibitor complex
(NE-1 PI) and cathepsin L in BAL fluid between asymptomatic
volunteers aged > 40 years who had emphysema detected by CT scans and
those who had a similar smoking history but did not have emphysema.
NE-1 PI originates mainly from neutrophils, while cathepsin L is
from macrophages. The immunologic levels of both proteases were
significantly higher in the subjects with subclinical emphysema; but,
when subjects aged < 60 years were chosen for comparison, there was
no difference between the two groups for cathepsin L, although the
difference remained for NE-1 PI.1,2 These results
suggested that neutrophils are more important than macrophages in the
early development of emphysema. We then used enzyme-linked
immunosorbent assays to determine the levels of chemotactic factors for
neutrophils and monocytes in BAL fluid. The factors studied were
interleukin (IL)-8 and leukotriene B4 as neutrophil
chemoattractants, and monocyte chemotactic protein-1 and macrophage
inflammatory protein-1 as monocyte chemoattractants. Only the level
of IL-8 in BAL fluid among these chemotactic factors had a strong
positive correlation with NE-1 PI (r = 0.74,
p < 0.01), and was significantly elevated in the subjects with
subclinical emphysema (p < 0.01). To examine the possibility that
alveolar macrophages are responsible for the elevation of IL-8 in BAL
fluid, we measured IL-8 in alveolar macrophage-conditioned media and
alveolar macrophage IL-8 messenger RNA by competitive reverse
transcriptase-polymerase chain reaction. We did not, however, find any
significant differences between the two groups in these measurements.
These studies indicate that neutrophils recruited and/or activated by
IL-8 appear to be crucial in the pathogenesis of subclinical emphysema.
The source of IL-8 remains to be determined.
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References
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Yoshioka, A, Betsuyaku, T, Nishimura, M, et al (1995) Excessive neutrophil elastase in bronchoalveolar lavage fluid in subclinical emphysema. Am J Respir Care Med 152,2127-2132[Abstract]
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Takeyabu, K, Betsuyaku, T, Nishimura, M, et al (1998) Cysteine proteinases and cystatin C in bronchoalveolar lavage fluid from subjects with subclinical emphysema. Eur Respir J 12,1033-1039[Abstract]
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Introduction
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