Biomedical Engineering Reference
In-Depth Information
stimulus), whereas the recruitment in response to Streptococcus pneumoniae
(a CD18 independent stimulus) was equal in both knock-out and wild-type
mice (133). Similar findings have been reported in P-selectin and E-selectin
knock-out mice, suggesting that these selectins are required in CD18 depen-
dent migration (as described earlier), but that they do not play a role in
CD18 independent migration. This finding has been supported further by
similar work where selectins were blocked with siayl-oligosaccharides
(which have a similar structure to selectin ligands). IgG immune complex
injury (found to be CD18 dependent in the lung) can be prevented by treat-
ing with sialyl compounds (134).
The complexities of these processes and their site and stimulus specifi-
city have received little attention in the study of COPD. Thus, to date, most
of the information is speculative and largely derived indirectly.
E. Migration in COPD
Patients with COPD have been shown to have increased neutrophil migra-
tion towards common chemoattractants in vitro. Burnett et al. (6) and
Stockley et al. (135) demonstrated an enhanced chemotactic response of
neutrophils from patients with COPD compared with neutrophils from
healthy controls toward fMLP, using the membrane filter chamber method,
and this was thought to reflect increased receptor expression. A further
potential mechanism for enhanced migration may be upregulation of adhe-
sion molecules, but in vitro studies have shown conflicting results. Noguera
et al. (7) measured MAC-1, LFA-1, and L-selectin expression on neutrophils
from controls and patients with COPD, prior- and poststimulation with
TNF-
a
. Neutrophils from patients with COPD had enhanced expression
of these adhesion molecules compared with controls, and differences were
even more pronounced following stimulation with chemoattractants. More
recently, Woolhouse et al. (136) demonstrated upregulation of CD11b
(a component of MAC1) on neutrophils from smokers with COPD com-
pared with controls. However, Gonzalez et al. (137) found no differences
between levels of adhesion molecules in smokers with and without airflow
obstruction. Thus, the issue remains unresolved at present.
The increased neutrophilic migration and degranulation seen in
COPD has led to a belief that neutrophils in COPD may be ''primed,'' per-
haps by inflammatory cytokines, so that they are more responsive, with an
increased ability to degranulate compared with those found in healthy indi-
viduals. This priming may occur during transmigration, and studies have
confirmed clear differences between neutrophils prior to and following
migration in healthy controls with increased expression of proteinases on
the cell surface, increased adhesion molecule expression, and enhancement
of the respiratory burst (96,138), although this has not been studied in
respiratory disease. Wherever it takes place, this priming cannot be caused
