The human monocyte has a Beta-glucan receptor which is functionally identical to the specific phagocytic receptor for particulate activators of the human alternative complement pathway. This proposal deals with the further characterization of the recently described Beta-glucan receptors. Research will be directed first at defining the exact specificity of ligands recognized by these monocyte phagocytic receptors with structurally characterized Beta-glucans, second, at determining the cellular distribution and numbers of Beta-glucan receptors with purified soluble radiolabeled ligands, third, at developing monoclonal anti-Beta-glucans for identifying the activating principles on particulate activators and for subsequent preparation of monoclonal anti-idiotypes for receptor isolation, and finally, at assessing various cellular responses that are activatable by Beta-glucan receptors. Long-term objectives are first, to use the defined Beta-glucans to study the initial cellular events that accompany glucan augmentation of numerous reported host defense systems, second, to compare the numbers of Beta-glucan receptors in patients with apparent phagocytic deficits to normal range values, third, to analyze by immunologic methods conformational epitopes that are physiologically active on pathogens and also potential reagents for eventual receptor isolation, and fourth, to identify the types of mediators that are generated in the absence of adaptive immunity. The characterization of these receptors, their ligand relatedness to activation of the alternative complement pathway, and their potential release of active mediators would define a novel system of nonimmune host defense which may be the key system that is temporarily overwhelmed in septic patients, thereby preventing rapid recovery despite adequate antibiotic therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI023542-02
Application #
3135805
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1986-09-30
Project End
1989-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115