Syndecan-1 attenuates lung injury following endotoxemia by lessens systemic and pulmonary TNFα/ADAM-17

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Research Article
American Journal of BioMedicine Volume 3, Issue 10, pages 597-618
Received: April 21, 2015; accepted: September 23, 2015; published: October 15, 2015

Holen Ramani a, Lawrence Nofer, Anurag Goepfert, Merton A Bernfield, Ralph M. Sandersonmail of corresponding author


Syndecans are cell surface or transmembrane coreceptors that modulate binding and signaling of cytokines, chemokines, and adhesion molecules, among other heparin-binding molecules. The objective of this dtudy is to investigate the protective role of the Syndecan-1 associated with endotoxemia-induced acute lung injury (ALI) in a mouse model. Wild-type (WT) and syndecan-1−/− (KO) mice were subjected to lung injury followed by resuscitation with lactated Ringer's (LR) or fresh frozen plasma orlactated Ringers (FFP) and compared shams. Lung tissue and blood were obtained after 3 h for analysis of lung injury and TNFα and ADAM-17 protein expression and activity. Lung injury was observed histologically in hematoxylin and eosin (HE) stained tissue sections, semi-quantified by lung tissue injury score, and the lung tissue mass alteration was measured by wet to dry weight ratio (W/D). mRNA expression levels of TNF-α and ADM-17 in lung tissue and  bronchoalveolar lavage fluid were studied with real time quantitative PCR (RT-PCR). FFP attenuated the pulmonary pathologic changes, inhibited neutrophil infiltration and proinflammatory cytokine production, and mitigated endothelial hyperpermeability compared with syndecan-1−/− (KO) mice. Furthermore, The activity and expression of TNFα and ADAM-17 significantly elevated in syndecan-1−/− (KO) mice. These  may help to explain the protective mechanism of syndecan-1 after lung injury.

Key words: Syndecan-1; Fresh frozen plasma; Lung injury; Endotoxemia

Copyright © 2015 by The American Society for BioMedicine and BM-Publisher, Inc.



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