| Abstract |
Pulmonary surfactant is a complex mixture of lipids
and proteins that constitutes the mobile liquid phase
covering the large surface area of the alveolar epithelium. It
maintains minimal surface tension within the lungs in order
to avoid lung collapse during respiration. Recent studies
have shown that components of Pulmonary surfactant also
function in the pulmonary host defence as immune
mediators. Pulmonary surfactant is composed of
phospholipids, neutral lipids and surfactant proteins (SP).
The SPs are divided into the hydrophobic SP-B and SP-C
and the hydrophilic SP-A and SP-D. SP-B and SP-C lower
the alveolar surface tension, while SP-A and SP-D are
primarily concerned with host-defense functions, acting as
immune mediators. Although pulmonary surfactant has the
potential to contribute to the pathogenesis of COPD, very
little work has been done in this field.
On the other hand, in a recent study of our laboratory,
detected Microsatellite DNA Instability (MSI) on G29802
(10q22) marker next to SP-A locus gene only in COPD
patients.
Taking into account all the evidence supporting that
surfactant, especially the immunomodulatory protein SP-A,
may be involved in the pathogenesis of COPD, we
investigate: 1) the expression levels (by western blot and
immunostaining) of SP-A in lung tissue of COPD patients in
comparison to non-COPD smokers with equivalent smoking
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history, and control non-smokers and 2) the relationship
between the expression levels of SP-A and the degree of
airway obstruction. To the best of our knowledge this is the
first study of SP-A expression in lung tissue of COPD
patients, non-COPD smokers and control non- smokers.
Western blots on lung tissue specimens from 60 male
subjects (32 COPD patients, 18 non-COPD smokers and 10
control non-smokers) for SP-A and the housekeeping actin,
have been carried out. In addition, by immunostaining the
expression pattern of the SP-A was determined in formalinfixed,
paraffin-embedded lung tissue sections from the same
subjects.
Western blots for SP-A showed decreased, but not
statistically significant, levels in COPD patients (0.6±0.7) in
comparison with non-COPD smokers (2.4±0.9), (p=0.12).
SP-A levels in control non-smokers were significantly higher
(4.8±0.05), (p>0.05). The immunostaining showed increased
overall number of pneumocytes type II cells in COPD
patients but decreased ratio of SP-A positive pneumocytes
type II to total pneumocyte type II cells, compared to control
smokers (p=0.001). This ratio was correlated with FEV1
(%pred), (r=0.490, p=0.001). The overall number of alveolar
macrophages was significantly higher in COPD patients
compared to non-COPD smokers (p=0.001). The percentage
of SP-A positive alveolar macrophages was higher in COPD
patients versus non-COPD smokers (p=0.002) and this
correlated to airway obstruction (FEV1% pred), (r=0.281,
p=0.04)
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In conclusion, our results indicate that alternate SP-A
expression could be another link to COPD pathogenesis and
highlights the need for further studies on surfactant
markers in COPD.
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Ιστοειδική έκφραση ανοσορυθμιστικών μεσολαβητών σε πνευμονικό ιστό ασθενών με Χ.Α.Π. και συσχέτιση με γενετική αστάθεια στο Μικροδορυφορικό D.N.A.
