Adhesion of neutrophils to microvasculature in acute inflammation involves lectin-carbohydrate adhesive interactions. These key events, occurring in response to tissue injury, may exert beneficial effects or result in tissue damage. Glycosylation of cell surface molecules generates ligands for the selectins, specifically the sialyl Lewis x oligosaccharide molecule. Recently, fucosyltransferase genes have been cloned and used to generate cultured cell lines with altered glycosylation phenotypes. Modification of the selectin ligand could result in a change in affinity for that selectin. These adhesive interactions are attractive targets for anti-inflammatory interventions, and require a better understanding of the structural basis of specificity. By constructing and analyzing recombinant glycoprotein molecules with engineered glycan moieties, the influences of the protein or glycan on the activity of the glycosyltransferases involved in the biosynthesis of sialyl Lewis x may be clarified. If these recombinant glycoproteins mimic endogenous molecules, they may inhibit in vitro adhesion occurring via these molecules and provide insight into therapeutic modalities. Established animal models of the inflammatory response provide a means of assessing the physiological adhesion- inhibiting capabilities of the recombinant glycoproteins.
Specific Aim 1 : To construct and analyze recombinant glycoproteins expressing carbohydrate ligands for selectins.
Specific Aim 2. To evaluate the in vivo function of recombinant sialylated glycoproteins.
Specific Aim 3. To evaluate the protective effects of recombinant sialylated glycoproteins in animal models of injury.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08HL003181-01
Application #
2211287
Study Section
Special Emphasis Panel (ZHL1-CCT-M (M1))
Project Start
1994-09-01
Project End
1999-08-31
Budget Start
1994-09-01
Budget End
1995-08-31
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Pathology
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109