COPD: Journal of Chronic Obstructive Pulmonary Disease, 8:79–95, 2011
ISSN: 1541-2555 print / 1541-2563 online
Copyright C ; Informa Healthcare USA, Inc.
DOI: 10.3109/15412555.2011.558542
ORIGINAL RESEARCH
Evaluation of Full-length, Cleaved and Nitrosylated Serum Surfactant
Protein D as Biomarkers for COPD
Annelyse Duvoix,1 Elena Miranda,2 Juan Perez,3 Grith L. Sorensen,4 Uffe Holmskov,4 Bruce C. Trapnell,5
Jens Madsen,6 Howard W. Clark,6 Lisa D. Edwards,7 Bruce E. Miller,7 Ruth M. Tal-Singer,7
and David A. Lomas1
Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building,
Cambridge, UK,1 Departamento Biologia e Biotecnologie, Università di Roma La Sapienza, Roma, Italy,2 Departamento de
Biología Celular, Genética y Fisiología, Facultad de Ciencias, Campus de Teatinos, Universidad de Málaga, Málaga, Spain,3
Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark,4
Cincinnati Children’s Hospital Medical Centre, Cincinnati, Ohio, USA,5 Child Health, Infection, Inflammation and Immunity
Division, University of Southampton, School of Medicine, Southampton General Hospital, Southampton, UK,6 GlaxoSmithKline,
King of Prussia, Pennsylvania, USA7
Chronic obstructive pulmonary disease (COPD) is a
multicomponent condition that is characterized by partially
reversible airflow obstruction. Serum surfactant protein D
(SP-D) is synthesized by type II pneumocytes and Clara cells
and participates in surfactant homeostasis and pulmonary host
defense. Serum levels of SP-D are raised in individuals with
COPD but there is no correlation between the serum level of
SP-D and the severity of airflow obstruction. Serum SP-D is
present in different forms that may have more utility as a
biomarker for COPD. We report here the development of new
monoclonal antibodies to full length and cleaved SP-D. We have
assessed these and existing antibodies in 98 individuals with
COPD recruited to the Evaluation of COPD Longitudinally to
Identify Predictive Surrogate Endpoints (ECLIPSE) cohort. Our
data show that neither monoclonal antibodies to full length
nor cleaved SP-D provide additional information over that
obtained with a polyclonal antibody. Moreover, levels of serum
nitrosylated-SP-D did not correlate with serum level of SP-D or
any clinical phenotype of COPD. The measurement of modified
SP-D is of limited value in characterising individuals with COPD.
Keywords: Surfactant Protein D, COPD, Biomarker, Monoclonal
antibodies
INTRODUCTION
Surfactant Protein D (SP-D) is a large hydrophilic protein
that is a member of the collectin family (1). It consists of a
short N-terminal domain, a collagen domain, a hydrophobic
neck and a calcium-dependant carbohydrate recognition do-
main (CRD). The association of 3 SP-D molecules, through
the formation of a triple helical collagen region and stabiliz-
ing interchain disulfide bonds, forms basic subunits, which
then associate into dodecamers linked by their N-terminal
regions (cruciform structure). SP-D is secreted into the lungs
by both type II alveolar cells and by Clara cells (2).
Correspondence to: David Lomas, Department of Medicine, University of Cambridge, Cambridge Institute for Medical Research, Wellcome
Trust/MRC Building, Hills Road, Cambridge CB2 0XY, UK phone: 01223 762818, fax: 01223 336827, e-mail: dal16@cam.ac.uk
