This proposal concerns the further characterization of the two bactericidal/permeability increasing proteins (BPI), one from human and one from rabbit polymorphonuclear leukocytes (PMN), that have been purified previously by this group. The isolated proteins are potently bactericidal toward a range of gram-negative bacterial species, but are non-toxic to gram- positive bacteria or eukaryotic cells. In intact PMN BPI appears to be the major 02-independent bactericidal agent against sensitive bacterial species.
Our specific aims are: I. To relate structure and function in the human and rabbit BPI by protein-analytical, immunological and recombinant DNA techniques. II. To examine further how the interaction of BPI with the gram-negative bacterial envelope relates to effects on viability and envelope structure and function. III. To explore further the biological importance of BPI in host- defense against gram-negative bacterial infections, using intact phagocytes, anti-BPI antibodies, nonbactericidal binding fragments of BPI and transfection of the BPI-gene into phagocytes that do not express this gene. The pursuit of these aims will rely on our previous work and the use of well-tested methods, including protein purification and radiolabeling, assays for BPI action, bacterial mutants, immunological methods, cells in culture. Our long-term objectives are to understand better leukocyte function and host-defense against infection, and should be met by the proposed studies on these two well-defined proteins. The planned scrutiny of structure-function relationships in BPI may help the design of new antibiotics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37DK005472-33
Application #
2134450
Study Section
Special Emphasis Panel (NSS)
Project Start
1978-06-01
Project End
1995-05-31
Budget Start
1994-06-01
Budget End
1995-05-31
Support Year
33
Fiscal Year
1994
Total Cost
Indirect Cost
Name
New York University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012
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