Premium
Circulating Endothelial Glycocalyx Fragments Impact Endothelial and Epithelial Repair after Septic Lung Injury
Author(s) -
Haeger Sarah,
Yang Yimu,
Zemans Rachel,
McClendon Jazelle,
Zhang Fuming,
Li Lingyun,
Linhardt Robert,
Schmidt Eric
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.863.9
Subject(s) - glycocalyx , lung , medicine , immunology
The endothelial glycocalyx is a heparan sulfate (HS)‐rich layer lining the vascular lumen. Sepsis‐induced glycocalyx degradation releases N‐sulfated HS fragments that circulate for days after sepsis onset. As N‐sulfated HS is known to augment pro‐repair growth factor signaling, we hypothesized that circulating HS would accelerate endothelial and epithelial repair after septic lung injury. We performed mass spectrometry to quantify N‐sulfated HS release into mouse plasma after cecal ligation and puncture. We performed intravital microscopy to confirm that i.v. fluorescent HS penetrated into the pulmonary interstitium, thereby accessing both pulmonary endothelium and endothelium. To determine the impact of circulating HS on pulmonary endothelial repair, we performed in vitro experiments (mouse lung microvascular endothelial cells) confirming that soluble HS augmented endothelial FGF2 signaling. Intravital microscopy demonstrated that this HS/FGF2 signaling accelerated glycocalyx reconstitution and endothelial barrier repair. To determine the impact of circulating HS on pulmonary epithelial repair, we performed in vitro experiments (using MLE‐12 cells, a mouse type II epithelial cell line) which surprisingly demonstrated that HS suppressed FGF‐FGFR signaling and delayed scratch repair. Our findings suggest divergent effects of circulating HS: pro‐reparative in endothelial cells, while suppressive of repair in the pulmonary epithelium. R01HL125371