SELECTIN/HEPARAN SULFATE INTERACTIONS IN ACUTE LUNG INJURY

University Of California San Diego, La Jolla CA

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Abstract

(Adapted from the Applicant's Abstract) Previous studies have shown that heparan sulfate proteoglycans expressed on vascular endothelial surf aces may be relevant ligands for L-selectin on neutrophils and monocytes and P-selectin on platelets and endothelial cells. The long range objective of this project is to evaluate whether the interaction of human lung endothelial cell heparan sulfate proteoglycans with L- and P-selectins plays a role in post-traumatic lung injury. In addition, therapeutic heparin can block L- and P-selectin dependent interactions in vitro, suggesting that natural and chemically-modified forms of heparin might be used to treat acute lung injury. The specific aims are to: (1) determine the expression of L- and P-selectins and their ligands in human pulmonary tissues in the setting of post-traumatic acute lung injury; (2) Examine proteoglycan expression under inflammatory traumatic acute lung injury; (3) Study the role of selectins and the effect of hind-limb ischemia-reperfusion; (4) study the structural requirements for the interactions of unfractionated heparin, low molecular weight heparins, and heparin fragments with L- and P-selectins.