ISRAEL SOCIETY OF PULMONARY MEDICINE ANNUAL ... - e-Med

Osteopontin: A Novel Glycoprotein Involved in Allergen-Induced Airway
Inflammation and Remodeling
Martin Kohan MSc, Raphael Breuer MD, and Neville Berkman MD
Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonary
Medicine
Hadassah – Hebrew University Medical Center, Jerusalem, Israel
Background: Airway remodeling is a central pathophysiological feature of chronic
asthma. Extracellular matrix (ECM) components not only provide structural support
to tissues, but also influence cellular migration, proliferation, differentiation,
apoptosis, and mediator release. ECM composition is altered in chronic asthmatic
lungs, suggesting that some ECM elements may be involved in the development of
airway remodeling. Osteopontin (OPN) is an ECM glycoprotein with profibrotic
properties; however its role in airway remodeling in asthma has not been explored.
Objective: Determine the expression and cellular sources of OPN and evaluate
whether this glycoprotein affects structural changes in a murine model of allergeninduced
airway inflammation and remodeling.
Methods: BALBc, C57BL/6 and OPN-knockout mice were sensitized and exposed to
ovalbumin (OVA) or saline inhalations for 5 weeks and sacrificed 24 hours after the
last inhalation. The following parameters of inflammation and remodeling were
assessed: bronchoalveolar (BAL) fluids differential cell counts, collagen production
(colorimetric biochemical assay), peribronchial smooth muscle content
(immunohistochemistry followed by image analysis), and mucus expression (PAS
staining). Matrix metalloproteinase-2 (MMP-2) activity was determined by
zymography. OPN expression in BAL and lung tissue was determined by PCR and
ELISA. Cellular sources and distribution of OPN were evaluated by
immunohistochemistry and immunofluorescence.
Results: OPN expression is upregulated in lung tissue and BAL fluids of OVAtreated
mice. Cells producing OPN include airway epithelium and cells of the
submucosal inflammatory infiltrate (T cells, eosinophils, and macrophages). OPN
deficiency is associated with reduction of lung collagen production, as well as
reduction of MMP-2 activity, peribronchial smooth muscle area and mucus
expression. Positive staining for OPN was also observed in bronchial tissue from
human asthmatic subjects.
Conclusion: Our results demonstrate that OPN expression is associated with
structural changes occurring in the lungs, suggesting a profibrotic role for this ECM
glycoprotein in airway remodeling in asthma.
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