Biomedical Engineering Reference
In-Depth Information
7
Neutrophils
Elizabeth Sapey and Robert A. Stockley
Lung Investigation Unit, Queen Elizabeth Hospital, Edgbaston,
Birmingham, U.K.
I.
INTRODUCTION
There is a wealth of data, supporting the neutrophil as the primary effector
cell in COPD and that neutrophil proteinases, especially neutrophil elastase
(NE), are responsible for the main pathological features. Studies have
shown that smokers have increased number of neutrophils in lung tissue
(1), sputum (2,3), and bronchoalveolar lavage fluid (BALF) (4). Gas transfer
(the most direct physiological measure of emphysema) has been shown to be
inversely proportional to the levels of neutrophil-associated markers, such
as myeloperoxidase (MPO) and human neutrophil lipocalin in patients with
COPD (5). Neutrophils from patients with COPD have increased chemotac-
tic response and proteolytic activity (6) and express more adhesion mole-
cules (7) compared with controls. Both clinical and subclinical emphysema
(noted on HRCT) is associated with an increase in NE and other neutrophil
proteins in BALF (8,9) and in established emphysema; severity is propor-
tional to NE immunoreactivity in tissue (10) and enzyme activity in BALF
(11). Furthermore, neutrophil enzymes have been shown to cause all compo-
nents of COPD, including emphysema mucous gland hyperplasia and mucus
hyper secretion (Table 1), and NE levels decline with smoking cessation (12),
the only intervention to date proven to slow progression of the disease.
The proteinase
=
antiproteinase theory has dominated research in
COPD. This states that
in health, proteinase activity is limited by
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