Expression, regulation and clinical significance of soluble and membrane CD14 receptors in pediatric inflammatory lung diseases

Background: Inflammatory lung diseases are a major morbidity factor
in children. Therefore, novel strategies for early detection of
inflammatory lung diseases are of high interest. Bacterial
lipopolysaccharide (LPS) is recognized via Toll-like receptors and
CD14. CD14 exists as a soluble (sCD14) and membrane-associated
(mCD14) protein, present on the surface of leukocytes. Previous
studies suggest sCD14 as potential marker for inflammatory
diseases, but their potential role in pediatric lung diseases
remained elusive. Therefore, we examined the expression, regulation
and significance of sCD14 and mCD14 in pediatric lung diseases.
Methods: sCD14 levels were quantified in serum and bronchoalveolar
lavage fluid (BALF) of children with infective (pneumonia, cystic
fibrosis, CF) and non-infective (asthma) inflammatory lung diseases
and healthy control subjects by ELISA. Membrane CD14 expression
levels on monocytes in peripheral blood and on alveolar macrophages
in BALF were quantified by flow cytometry. In vitro studies were
performed to investigate which factors regulate sCD14 release and
mCD14 expression. Results: sCD14 serum levels were specifically
increased in serum of children with pneumonia compared to CF,
asthma and control subjects. In vitro, CpG induced the release of
sCD14 levels in a protease-independent manner, whereas LPS-mediated
mCD14 shedding was prevented by serine protease inhibition.
Conclusions: This study demonstrates for the first time the
expression, regulation and clinical significance of soluble and
membrane CD14 receptors in pediatric inflammatory lung diseases and
suggests sCD14 as potential marker for pneumonia in children.