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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL023584-24
Application #
6564820
Study Section
Project Start
2001-12-01
Project End
2002-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
24
Fiscal Year
2002
Total Cost
$40,863
Indirect Cost

  Institution

Name
University of California San Diego
Department
Type
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Kerr, Kim M; Auger, William R; Marsh, James J et al. (2012) Efficacy of methylprednisolone in preventing lung injury following pulmonary thromboendarterectomy. Chest 141:27-35
Dunzendorfer, Stefan; Lee, Hyun-Ku; Soldau, Katrin et al. (2004) Toll-like receptor 4 functions intracellularly in human coronary artery endothelial cells: roles of LBP and sCD14 in mediating LPS responses. FASEB J 18:1117-9
Lee, Hyun-Ku; Dunzendorfer, Stefan; Tobias, Peter S (2004) Cytoplasmic domain-mediated dimerizations of toll-like receptor 4 observed by beta-lactamase enzyme fragment complementation. J Biol Chem 279:10564-74
Spragg, Roger G; Ponganis, Paul J; Marsh, James J et al. (2004) Surfactant from diving aquatic mammals. J Appl Physiol 96:1626-32
Dunzendorfer, Stefan; Lee, Hyun-Ku; Soldau, Katrin et al. (2004) TLR4 is the signaling but not the lipopolysaccharide uptake receptor. J Immunol 173:1166-70
Spragg, Roger G; Lewis, James F; Wurst, Wilhelm et al. (2003) Treatment of acute respiratory distress syndrome with recombinant surfactant protein C surfactant. Am J Respir Crit Care Med 167:1562-6
Thompson, Patricia A; Tobias, Peter S; Viriyakosol, Suganya et al. (2003) Lipopolysaccharide (LPS)-binding protein inhibits responses to cell-bound LPS. J Biol Chem 278:28367-71
Tapping, Richard I; Tobias, Peter S (2003) Mycobacterial lipoarabinomannan mediates physical interactions between TLR1 and TLR2 to induce signaling. J Endotoxin Res 9:264-8
Bussolati, Benedetta; David, Salvatore; Cambi, Vincenzo et al. (2002) Urinary soluble CD14 mediates human proximal tubular epithelial cell injury induced by LPS. Int J Mol Med 10:441-9
Li, Jiali; Marsh, James J; Spragg, Roger G (2002) Effect of CTP:phosphocholine cytidylyltransferase overexpression on the mouse lung surfactant system. Am J Respir Cell Mol Biol 26:709-15

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