Abstract
BackgroundInflammatory 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.MethodssCD14 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.ResultssCD14 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.ConclusionsThis 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.
Highlights
Inflammatory lung diseases of infective or non-infective origin are among the leading morbidity and mortality factors in children and require early diagnosis for specific treatment to prevent disease progression and chronic lung remodelling [1,2]
Similar to soluble form of CD14 (sCD14) levels, mCD14 expression levels on bronchoalveolar lavage fluid (BALF) macrophages were increased in pneumonia patients compared to Cystic fibrosis (CF), asthma and control children (Figure 4)
Since our results indicated that sCD14 serum levels are increased in bacterial pneumonia, we analyzed the usefulness of sCD14 serum levels to differentiate bacterial pneumonia from CF, asthma and healthy controls in comparison to the traditionally used markers C-reactive protein (CRP) and white blood cell count (WBC)
Summary
Inflammatory lung diseases of infective or non-infective origin are among the leading morbidity and mortality factors in children and require early diagnosis for specific treatment to prevent disease progression and chronic lung remodelling [1,2]. Novel strategies for early detection of inflammatory and infective lung diseases in childhood are of high interest. CD14 exists as a soluble (48/56 kDa) and membraneassociated glycosylphosphatidylinositol (GPI)-anchored (55 kDa) protein, present on the surface of monocytes, macrophages, dendritic cells and neutrophils [4,8]. The soluble form of CD14 (sCD14) is produced either by proteolytic cleavage or by secretion without the GPI moiety by monocytes [9,10]. Inflammatory lung diseases are a major morbidity factor in children. Novel strategies for early detection of inflammatory lung diseases are of high interest. 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. We examined the expression, regulation and significance of sCD14 and mCD14 in pediatric lung diseases
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