CHEST Original Research

COPD

Altered Surfactant Protein-A Expression

in Type II Pneumocytes in COPD
Eleni M. Vlachaki, MD; Anastassios V. Koutsopoulos, MD, PhD; Nikolaos Tzanakis, MD,
PhD; Eirini Neofytou, MSc; Marianna Siganaki, MD; Ioannis Drositis, MD;
Andreas Moniakis, MD; Sophia Schiza, MD, PhD; Nikolaos M. Siafakas, MD, PhD, FCCP;
and Eleni G. Tzortzaki, MD, PhD, FCCP

Background: Pulmonary surfactant protein A (SP-A) is a lectin, with multiple functions that con-
tribute to innate host defense and the regulation of the inflammatory process in the lung. In
normal conditions, SP-A seems to protect against the effects of smoking. However, studies in smokers
with or without COPD are limited.
Methods: Western blots on lung tissue specimens from 60 male subjects (32 patients with COPD,
18 smokers without COPD, and 10 control nonsmokers) for SP-A and the housekeeping protein
actin were carried out. Additionally, the SP-A expression pattern was evaluated by immuno-
histochemistry in formalin-fixed, paraffin-embedded lung tissue sections from the same subjects.
Results: Western blots revealed significantly higher SP-A levels in control nonsmokers (4.8 6 0.05)
when compared with patients with COPD (0.6 6 0.7) and smokers without COPD (2.4 6 0.9),
(P , .05). However, differences that were not statistically significant were observed in SP-A levels
among the patients with COPD and the smokers without COPD (P 5 .12). The immunohistochem-
ical examinations showed an increase in the overall number of type II pneumocytes per high-
power field in patients with COPD, but a decreased ratio of SP-A positive type II pneumocytes to
total type II pneumocytes, compared with smokers without COPD (P 5 .001). This ratio was also
correlated with FEV1 (percent predicted [% pred]), (r 5 0.490, P 5 .001). The overall number of
alveolar macrophages per high-power field was significantly higher in patients with COPD com-
pared with smokers without COPD (P 5 .001). The ratio of SP-A positive alveolar macrophages
was increased in patients with COPD when compared with smokers without COPD (P 5 .002),
while this was correlated with airway obstruction (FEV1, % pred) (r 5 0.281, P 5 .04).
Conclusions: Our results indicate that altered SP-A expression could be another link to COPD
pathogenesis and highlights the need for further studies on surfactant markers in COPD.
CHEST 2010; 137(1):3745

Abbreviations: (% pred) 5 percent predicted; SP 5 surfactant protein; TTF 5 thyroid transcription factor-1

Pulmonary surfactant is a complex mixture of lipids

and proteins synthesized mainly by type II pneu-
mocytes.1 Four surfactant proteins (SPs) have been
defined: SP-A, SP-B, SP-C, and SP-D.1,2 SPs were
initially thought to play a key role in the biophysical
Manuscript received May 6, 2009; revision accepted July 14, 2009.
Affiliations: From the Department of Thoracic Medicine (Drs
Vlachaki, Tzanakis, Neofytou, Schiza, Siafakas, and Tzortzaki, and
Ms Siganaki), the Department of Pathology (Dr Koutsopoulos),
and the Department of Thoracic Surgery (Drs Drositis and
Moniakis), University Hospital of Heraklion, Medical School,
University of Crete, Greece.
Part of this article has been presented in abstract form (Vlachaki
E, Tzortzaki EG, Koutsopoulos A, et al. Proc Am Thorac Soc.
2006:A624).
behavior of the lung. However, the newly established
immunomodulatory properties of lectins SP-A and
SP-D elucidated their important role in a number of
lung diseases.1 Although lectins have the potential to
Funding/Support: The present study was supported by a Grant
of Hellenic Thoracic Society.
Correspondence to: Eleni Tzortzaki, MD, PhD, FCCP, Depart-
ment of Thoracic Medicine, University Hospital of Heraklion,
Medical School, University of Crete, 71110 Heraklion, Crete, Greece;
e-mail: tzortzaki@med.uoc.gr
2010 American College of Chest Physicians. Reproduction
of this article is prohibited without written permission from the
American College of Chest Physicians (www.chestjournal.org/
site/misc/reprints.xhtml).
DOI: 10.1378/chest.09-1029

www.chestjournal.org CHEST / 137 / 1 / JANUARY, 2010 37

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 contribute to the pathogenesis of COPD, little work
has been done in this field.2
COPD is a slowly progressive disease character-
ized by reduced maximum expiratory flow and slow
forced emptying of the lungs, features that are not
fully reversible.3 Abnormal inflammatory responses
to several noxious agents (mainly smoke from ciga-
rettes), the involvement of a variety of inflammatory
cells and cytokines, and the persistent destructive
oxidative process, accused of being the pathogenesis
of COPD, may affect the composition and the func-
tion of surfactant.4 It has been also shown that smoking,
the major cause of COPD, might affect surfactant
homeostasis and function.5 Along this line, Otto-
Verberne and colleagues4 reported a protective
effect of pulmonary surfactant on elastase-induced
emphysema in mice. Moreover, Honda et al6 stud-
ied the levels of immunomodulatory SP-A and
SP-D in BAL and reported decreased levels of SP-A
and SP-D in smokers compared with nonsmokers.
These results have recently been confirmed by
Betsuyaku et al,7 whereas Guo et al8 reported that
certain SP-A alleles may increase susceptibility
to COPD.
Nevertheless, current concepts suggest that the
various surfactant proteins differ both in their local-
ization and biologic action; for example, the lectins
SP-A and SP-D have been related to the host
defense of the lung.9-11 In the present study, we spe-
cifically focused on the immunomodulatory protein
SP-A, considering its important role in the pulmo-
nary host defense.1,2 In normal conditions, SP-A
is generally beneficial in protecting the lungs from
oxidants and inflammatory and infectious stress.1,2
However, SP-A immunity functions seem to be
impaired in chronic smokers,5-7 which may play a cru-
cial role in the development of COPD. Furthermore,
we have previously reported microsatellite DNA
instability in patients with COPD in G29802 marker.12
Microsatellite marker G29802 is located on the
10q22 chromosomal region next to SP-A1 gene. We
hypothesized that microsatellite DNA instability in
G29802 marker in patients with COPD could be
an indication of a deficient mismatch repair in the
region and perhaps a disruption of the adjacent
SP-A gene.
On this basis, we attempted to explore (1) the
SP-A protein levels, using Western blots and
immunohistochemistry in smokers with or without
COPD and in control nonsmokers, and (2) the
relationship between the SP-A expression levels
and the degree of airway obstruction. To the best
of our knowledge, this is the first study to evaluate
the SP-A expression in lung biopsies from patients
with COPD, smokers without COPD, and control
nonsmokers.
38
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Materials and Methods
Subjects
The study population comprised 60 subjects who underwent
lung resection for a solitary peripheral nodule of malignant car-
cinoma. Spirometric evaluation was performed according to
standard protocols 1 week before lobectomy. Patients who had
a severe COPD exacerbation or lower respiratory tract infec-
tion within 4 weeks before their entrance in the study were
excluded.
Three groups were defined: 32 smokers with COPD, 18 smok-
ers without COPD and without lung function impairment, and 10
control nonsmokers. The American Thoracic Society/European
Respiratory Society Consensus Statement13 was used for the diag-
nosis and assessment of severity for the patients with COPD.
Informed consent was obtained from all subjects, and the proto-
col was approved by the medical ethics committee of the Univer-
sity Hospital of Heraklion in Crete.
Human Tissue Preparation
Human lung tissue samples (two or three blocks) were
obtained from all subjects, derived from the subpleural parenchyma
at least 5 cm away from the solitary nodule. During surgery, all
patients received general anesthesia under controlled mechani-
cal ventilation. Tissue samples for Western blots were immedi-
ately frozen in liquid nitrogen and stored at 280C until use. Tis-
sue samples for immunohistochemistry were immediately fixed
in 10% buffered formalin for at least 24 h. After fixation, each
tissue block was embedded in paraffin. Sections 5 mm thick were
cut following routine procedures. To overcome possible tissue
volume differences between different groups when counting
various cells (eg, pneumocytes and alveolar macrophages), we
evaluated the ratios of SP-A positive pneumocytes to total pneu-
mocytes and the ratios of SP-A-positive macrophages to total
macrophages.
Western Blots
Western blot detection of SP-A and actin was performed using
standard procedures. In detail, lung tissue specimens from all
subjects were homogenized to obtain the corresponding pro-
tein extracts. The protein lysate was added to one-third volume
of sodium dodecyl sulfate-preparation buffer (NuPAGE LDS
4 3 LDS Sample Buffer; Invitrogen Corp; Carlsbad, CA). Sample
preparations of each lung protein sample (50 ng) were separated
using 12.5% sodium dodecyl sulfate-polyacrylamide gel electro-
phoresis under reducing conditions. The gels were then trans-
ferred using electrophoresis to a nitrocellulose membrane. Immuno-
detection was done using a primary mouse anti-SP-A antibody
(PE-10; Dako, Ltd; Hellas, Greece), an exposure time of 1 min,
and enhanced chemiluminescence. The protein presence was
assessed using the mouse antiactin antibody (MAB 1501; Chemi-
con; Temecula, CA). The lanes of the blotted membranes were
quantified using Photoshop Image Analysis Software (CS2, Adobe
Systems Inc; San Jose, CA).
Immunohistochemistry
Immunostaining of SP-A and thyroid transcription factor-1
(TTF-1) in formalin-fixed, paraffin-embedded lung tissue sec-
tions was carried out using the biotin-based kit Link-Label
(IHC Detection Systems; Biogenix; San Ramon, CA) according
to manufacturer instructions. The monoclonal mouse antihu-
man SP-A, clone PE-10 antibody (Dako Ltd) was used in a 1:50
dilution at room temperature for 1 h. The monoclonal mouse
Original Research
 anti-TTF-1 antibody (Santa Cruz Biotechnology, Inc) was used
on adjacent serial sections to count the total type II pneumo-
cytes and SP-A positive type 2 cells. Sections were counter-
stained with Mayers hematoxylin. Negative control experi-
ments for nonspecific binding were performed with preimmune
serum.
Quantification of the Immunohistochemical Reaction
The evaluation of the total type II pneumocytes (columnar
alveolar lining cells), alveolar macrophages (irregularly distributed
in the alveoli with foamy cytoplasm and indented nuclei), and
SP-A-positive cells stained in purple (type II pneumocytes and
macrophages) was performed using a grid with dimensions 10 3 10
for light microscopy (Olympus; Olympus America Inc.; Center
Valley, PA), at 340 magnification (manual counting). Two observers
(E.M.V., A.V.K.) specialized in lung pathology examined the
sections independently, without prior knowledge of the subjects
clinical data. The interobserver variability of measurements was
expressed as the % coefficient of variation. The interobserver
coefficient of variation was , 10%.
Twenty microscopic fields of each slide, in a cross configura-
tion, were evaluated for all subjects. The results were expressed in
cells per millimeter squared.
Statistical Analysis
Clinical characteristics are presented as mean 6 SD and cell
characteristics as median (range) unless stated otherwise. Differ-
ences between the groups of subjects were tested using the Mann-
Whitney U test for non-normal distributed variables and the Stu-
dent t test for normal variables for independent groups. Pearsons
for normal or Spearmans for non-normal correlation coefficients
were used to evaluate the associations between variables. The
statistical software SPSS Version 15 for Windows (SPSS Inc.;
Chicago, IL) was used for the entire analysis. A P value of , 0.05
was considered statistically significant.
Results
The anthropometric characteristics and spirometric
values of patients with COPD, smokers without COPD,
and control nonsmokers are shown in Table 1. Western
blot analysis showed SP-A levels were decreased,
although not statistically significant, in patients with
COPD (0.6 6 0.7) in comparison with smokers with-
out COPD (2.4 6 0.9), (P 5 .12). SP-A levels in control
nonsmokers were significantly higher (4.8 6 0.05),
(P , .05) in comparison with smokers with or without
COPD (Fig 1).
Table 1Anthropometric Characteristics and Spirometric Values of Study Subjects
Smokers With COPD Smokers Without COPD
Sex, M/F 32/0
Age, y 64 6 6.5
Smoking, P-Y 59 6 20.4
FEV1, % pred 63.6 6 15.5
FVC, % pred 79.3 6 17.6
FEV1/FVC, % 62.3 6 6.2
M/F 5 male/female; NS 5 not significant; P-Y 5 pack-years of smoking.
aComparison between smokers with COPD and smokers without COPD.
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Immunostaining Images
Figure 2 shows representative SP-A immuno-
stained images of lung tissue in a patient with COPD
(Fig 2A), in a smoker without COPD (Fig 2B), and in
a control nonsmoker (Fig 2C). Figure 3 shows positive
TTF-1 immunostained images of type II pneumo-
cytes in a patient with COPD (Fig 3A) and in a smoker
without COPD (Fig 3B). Alveolar macrophages were
TTF-1 negative.
Type II Pneumocytes and SP-A Expression
Figures 2A and 2B show representative SP-A
immunostaining of type II pneumocytes in lung tissue
sections from a patient with COPD and a smoker
without COPD, respectively. The total number of
type II pneumocytes was higher in patients with
COPD in comparison with smokers without COPD,
as shown in Figure 4 (P 5 .002). The ratio of SP-A-
positive type II pneumocytes (SP-A-positive type II
pneumocytes/total type II pneumocytes, expressed
as %) was higher in smokers without COPD com-
pared with patients with COPD (P 5 .001) (Fig 4B).
Alveolar Macrophages and SP-A Expression
Figures 2A and 2B show SP-A positive alveolar
macrophages from a patient with COPD and a smoker
without COPD. The total number of macrophages
per millimeter squared was significantly higher in
patients with COPD compared with smokers without
COPD (P 5 .001) ( Fig 5A).
The ratio of SP-A-positive alveolar macrophages
(SP-A-positive alveolar macrophages/total alveolar
macrophages, expressed as a percentage) was sig-
nificantly higher (P 5 .002) in patients with COPD
compared with smokers without COPD (Fig 5B). In
addition, the scatter of the values of the ratio in patients
with COPD was smaller (Fig 5B).
Correlation of SP-A Expression
The ratio of SP-A-positive type II pneumocytes to
total type II pneumocytes was significantly corre-
lated with FEV1 values (r 5 0.490, P 5 .001) (Fig 6A).
Control Nonsmokers P Valuea
18/0 10/0
56.5 6 10.2 57.6 6 16.7 .03
49.1 6 26.7 NS
94.7 6 12.4 101.2 6 14 .0001
91 6 12.5 95.8 6 15 .02
81.4 6 4.7 83.4 6 2 .0001
CHEST / 137 / 1 / JANUARY, 2010 39
 Figure 1. Representative Western blots of SP-A and actin in
human lung tissues from two patients with COPD, one smoker
without COPD, and one control nonsmoker. Immunodetection
was done using primary mouse anti-SP-A antibody (A). Quantita-
tive analysis (mean 6 SD) for SP-A normalized to actin showed
decreased but not statistically significant levels in patients with
COPD in comparison with smokers without COPD, whereas in
control nonsmokers, the SP-A levels were significantly higher than
in smokers with or without COPD (B). NS 5 not significant differ-
ence (P 5 .12) between patients with COPD and smokers without
COPD; SP-A 5 surfactant protein A. ** 5 significant difference
(P , .05) between patients with COPD and control nonsmokers.

In Figure 6A, we illustrated that the decreased SP-A

ratio was related with a higher degree of obstruction
(lower FEV1 percent predicted [% pred]). The ratio
of SP-A-positive alveolar macrophages to total alve-
olar macrophages was significantly (r 5 0.281,
P 5 .04) correlated with FEV1 (Fig 6B). No signifi-
cant correlation between the total number of SP-A-
positive cells and age was found in any of the
subjects.

Discussion
To our knowledge, this study is the first to evalu-
ate protein levels and tissue distribution of SP-A in
human lung biopsies from patients with COPD,
smokers without COPD, and control nonsmokers
using an adequate sample size and two different
experimental approaches for each patient. SP-A
levels, as revealed by Western blots, reflected the
overall protein expression from the homogenized
lung extracts (including SP-A from pneumocytes
Figure 2. Immunostaining of SP-A in human lung tissue (origi-
nal magnification 3400). A positive SP-A hyperplastic type II
pneumocyte [PN II (+)] stained in pink, negative hyperplastic
SP-A type II pneumocytes [PN II (-)] stained in blue, and posi-
tive alveolar macrophages [MACR (+)] stained in purple, from a
representative patient with COPD (A). A hyperplastic positive
SP-A type II pneumocyte [PN II (+)] cell stained in purple, a
negative SP-A type I pneumocyte [PN I (-)] stained in blue, and
positive alveolar macrophages [MACR (+)] stained in purple,
from a representative smoker without COPD (B). Positive SP-A
pneumocytes [PN (+)] stained in purple, from a representative
control nonsmoker (C). See Figure 1 legend for expansion of
other abbreviations.

40 Original Research

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 Figure 3. Positive TTF-1 immunostaining in type II pneumocytes [PN II (+)] in a patient with COPD
(A) and in a smoker without COPD (B). In both A and B, the alveolar macrophages [MACR (-)] were
TTF-1 negative (original magnification 3400). TTF-1 5 thyroid transcription factor-1.

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 Figure 4. Total number of pneumocytes II per millimeter squared in patients with COPD and in smok-
ers without COPD (A). SP-A positive pneumocytes II (expressed as a percentage of the total pneumo-
cytes II) in patients with COPD and in smokers without COPD (B). Lines represent median values. 5
patients with COPD; 5 smokers without COPD (control subjects). See Figure 1 legend for expansion
of other abbreviations.

and alveolar macrophages), while immunohistochem-
ical examinations further identified the specific cell
subtypes expressing SP-A protein in the human lung.
Western blots revealed significantly higher SP-A
levels in control nonsmokers compared with patients
with COPD and smokers without COPD (P , .05).
However, differences that were not statistically sig-
nificant were observed in SP-A levels among patients
with COPD and smokers without COPD (P 5 .12),
( Fig 1). Interestingly, although immunostaining
revealed increased overall numbers of type II pneumo-
cytes in patients with COPD in comparison with
smokers without COPD (Fig 4A), the ratio of SP-A-
positive type II pneumocytes to total type II pneu-
mocytes was decreased in COPD patients (Fig 4B).
In addition, the decreased SP-A ratio in patients with
COPD was related to lower FEV1 (% pred), (Fig 6A).
Furthermore, the overall number of alveolar mac-
rophages was significantly higher in patients with
COPD compared with smokers without COPD
(Fig 5A), whereas the ratio of SP-A-positive mac-
rophages to the total macrophages was higher in
patients with COPD. This was also correlated with
airway obstruction (FEV1 % pred) (Fig 6B).
The pathogenetic role of surfactant was first
described in infant respiratory distress syndrome,
in which surfactant deficiency induced the disease.14,15
Later, surfactant biochemical, functional, and immuno-
modulatory abnormalities were reported in certain
other lung diseases, including COPD.14,16
Increased Type II Pneumocytes in COPD
Our results revealed an increased number of type
II pneumocytes in patients with COPD compared
with smokers without COPD. This result was expected
because of the known extensive tissue damage in
COPD and is also in agreement with the mechanical

Figure 5. Total number of macrophages per millimeter squared in patients with COPD and in smokers
without COPD (A). SP-A positive macrophages (expressed as % of the total number of macrophages) in
patients with COPD and in smokers without COPD (B). Lines represent median values. 5 patients
with COPD; 5 smokers without COPD. See Figure 1 legend for expansion of abbreviation.

42 Original Research

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 Figure 6. The relationship between SP-A-positive pneumocytes II expressed as % of the total pneumo-
cytes II and FEV1 (% pred) in patients with COPD and in smokers without COPD (A). The relationship
between SP-A-positive alveolar macrophages expressed as % of total alveolar macrophages and FEV1 (%
pred) in all subjects (B). 5 patients with COPD; 5 smokers without COPD. See Figure 1 legend for
expansion of other abbreviations.
injury hypothesis.10,11 Increased numbers of type
II pneumocytes have been reported in previous
studies, especially in rats after induced lung
injury.5,17 The alveolar epithelium, when injured by
cigarette smoke, initiates repair responses of dif-
ferentiation and proliferation of cells to cover the
defect from the injury.18,19 Type II pneumocytes
proliferate during lung injury and chronic inflam-
matory states,19 such as COPD, to produce type 1 cells.
Furthermore, type II pneumocytes produce spe-
cific molecules, enzymes, and proteins, such as SP-A,
which participate in lung defense against noxious
agents.20,21
Decreased SP-A Expression in Type II
Pneumocytes in COPD Was Related With
the Degree of Airway Obstruction
Interestingly, we have found a decreased ratio of
SP-A-positive type II pneumocytes (SP-A-positive
type II pneumocytes/total type II pneumocytes) in
patients with COPD compared with smokers without
COPD (Fig 4B), and this was related to a higher
degree of obstruction (Fig 6A). One explanation could
be that SP-A levels are lower in patients with COPD
as a result of disease-related epithelial destruction
that depletes the type II pneumocytes and clara
cells responsible for SP-A production. In support of
this scenario, the degree of airway obstruction was
inversely correlated with the SP-A levels. In normal
conditions, SP-A is generally beneficial in protecting
the lungs from oxidants and inflammatory and infec-
tious stress.21 It is also involved in the clearance of
apoptotic and necrotic cells.20 However, studies have
shown that host defense functions of surfactant may
be impaired in the chronic smoker.7,22 Decreased lev-
els of SP-A were reported in BAL fluid from chronic
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smokers, suggesting that this may contribute to the
increased prevalence of respiratory infections,6
impaired efferocytosis (removal of apoptotic bodies),
and abnormal tissue remodeling.20 Two recent studies
by Hu et al23,24 reported decreased SP-A levels in the
lung tissue and lavage fluid of rats after chronic ciga-
rette smoke exposure, concluding that cigarette smoke
might have important effects on SP-A metabolism
and host defense functions.
The association between cigarette smoke, innate
immunity, lung inflammation, and COPD pathogen-
esis has been extensively studied, and several theories
have been proposed.25-28 In the susceptible smoker,
continuous exposure initially affects the lung epithe-
lial barrier system and, in particular, its cellular com-
ponent via repeated oxidative stress, which may result
in oxidative DNA damage and acquired somatic
mutations of these cells.27-30 In previous studies, we
have reported acquired genetic instability in the G29802
marker in patients with COPD,12,31, hypothesizing
that this could be an indication of a deficient DNA
mismatch repair in the region and perhaps a disrup-
tion of the adjacent SP-A gene. The decreased SP-A
expression in type II pneumocytes in patients with
COPD, as revealed by this study, could support our
initial hypothesis.
SP-A Expression in Alveolar Macrophages
In accordance with previous studies, we found
increased numbers of macrophages in the lung paren-
chyma of patients with COPD.32 We further reported
higher numbers of SP-A-positive alveolar macrophages
in patients with COPD than in smokers without
COPD. Moreover, the ratio of SP-A-positive alveolar
macrophages to total alveolar macrophages was sig-
nificantly correlated with FEV1(Fig 6B).
CHEST / 137 / 1 / JANUARY, 2010 43
 A possible explanation for the increased SP-A
amounts found in the alveolar macrophages of
patients with COPD could come from SP-A fractions
scavenged from the alveolar space. This could reflect
either an impaired mechanism of SP-A production or
an altered turnover of SP-A in type II pneumocytes
in patients with COPD, or both. A number of stud-
ies have shown that SP-A has the potential to stimu-
late macrophages and to increase phagocytosis of
various bacteria, viruses, allergens, and apoptotic
cells. Thereby, functioning as opsonin could also
enhance the uptake of SP-A fractions by alveolar
macrophages.2,20
Our study has some limitations. First, although the
study subjects were well characterized, for feasibility
reasons the lung tissue specimens were obtained only
from subjects undergoing resection for lung cancer.
Although it is known that pulmonary malignancy
could affect surfactant expression,33,34 all subjects
included in this study had the same comorbidity (ie,
lung cancer). Second, surgical lung biopsies were not
obtained from patients with more advanced COPD.
This could have led to underestimation of our results
because our data suggested that these patients prob-
ably could express even lower SP-A levels. Third, the
median age of the patients with COPD was higher
than that of the smokers without COPD (P 5 .03),
although no significant correlation between total SP-A
expression and age was found. Interestingly, a previ-
ous study by Betsuyaku et al7 reported that middle-
aged or elderly smokers with emphysema had lower
levels of SP-A in BAL fluids when compared with
young subjects and with middle-aged or elderly smok-
ers without emphysema.
Previous investigators have reported controversial
results on the SP-A levels in lavage fluid or serum
of smokers and patients with COPD. Some studies
reported decreased SP-A levels6,7 and others increased35
or unchanged levels.36 Studies in rats exposed to ciga-
rette smoke did not show changes in SP-A levels in
BAL fluid,17 but rat alveolar type 2 cells in culture
showed impaired surfactant secretion.5 On the other
hand, Shibata et al37 reported elevated SP-A expres-
sion in the lungs of cigarette smoke-exposed mice
compared with air-exposed mice. Ohlmeier et al38
reported increased SP-A levels in lung tissue and
induced sputum from patients with COPD compared
with normal or fibrotic lung tissue, whereas no such
change was observed in the levels of other surfactant
proteins (eg, SP-B, SP-C, SP-D).
Conclusions
We have demonstrated an altered SP-A expression
in patients with COPD that is correlated with airway
44
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obstruction. The reported relationship, although not
direct cause and effect, may suggest either an abnor-
mal production of SP-A in type II pneumocytes or
an augmented SP-A turnover in the lungs of patients
with COPD. Nevertheless, these are interesting
hypotheses that need further exploration.
Acknowledgments
Author contributions: Dr Vlachaki: contributed to the acquisition,
analysis, and interpretation of data.
Dr Koutsopoulos: contributed to the acquisition, analysis, and
interpretation of data.
Dr Neofytou: contributed to the acquisition, analysis, and
interpretation of data.
Ms Siganaki: contributed to the acquisition, analysis, and
interpretation of data.
Dr Drositis: contributed to the acquisition of data.
Dr Moniakis: contributed to the acquisition of data.
Dr Schiza: contributed to the acquisition of data.
Dr Siafakas: contributed to interpretation of data and critically
revised the article.
Dr Tzanakis: contributed to interpretation of data and critically
revised the article.
Dr Tzortzaki: contributed to conception and design of the study,
the analysis and interpretation of data, and drafted the submitted
article.
Financial/nonfinancial disclosures: The authors have reported
to CHEST that no potential conflicts of interest exist with any
companies/organizations whose products or services may be
discussed in this article.
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