Loss of endothelial sulfatase-1 after experimental sepsis attenuates subsequent pulmonary inflammatory responses.

Loss of endothelial sulfatase-1 after experimental sepsis attenuates subsequent pulmonary inflammatory responses. Am J Physiol Lung Cell Mol Physiol. 2019 Aug 28;: Authors: Oshima K, Han X, Ouyang Y, El Masri R, Yang Y, Haeger SM, McMurtry SA, Lane TC, Davizon-Castillo P, Zhang F, Yue X, Vivès RR, Linhardt RJ, Schmidt EP Abstract Sepsis patients are at increased risk for hospital-acquired pulmonary infections, potentially due to post-septic immunosuppression known as the compensatory anti-inflammatory response syndrome (CARS). CARS has been attributed to leukocyte dysfunction, with an unclear role for endothelial cells. The pulmonary circulation is lined by an endothelial glycocalyx, a heparan sulfate-rich layer essential to pulmonary homeostasis. Heparan sulfate degradation occurs early in sepsis, leading to lung injury. Endothelial synthesis of new heparan sulfates subsequently allows for glycocalyx reconstitution and endothelial recovery. We hypothesized that remodeling of the reconstituted endothelial glycocalyx, mediated by alterations in the endothelial machinery responsible for heparan sulfate synthesis, contributes to CARS. 72 hours after experimental sepsis, coincident with glycocalyx reconstitution, mice demonstrated impaired neutrophil and protein influx in response to intratracheal lipopolysaccharide (LPS). The post-septic reconstituted glycocalyx was structurally remodeled, with enrichment of heparan sulfate disaccharid...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research