This research involves examining, immunologically and biochemically, the ontogeny of the human Fc-gamma Receptor (Fc-gamma R) that binds immune complexes. A previously isolated, mouse monoclonal antihuman neutrophil Fc R antibody, 3GB, and its Fab fragment inhibit the binding of soluble immune complexes or the binding and phagocytosis of antibody-coated erythrocytes to polymorphonuclearneutrophil leukocytes (PMN). The antigen recognized by 3G8 is present on all peripheral blood PMN, mature cells from patients with chronic myelogenous leukemia (CML), and 15% of lymphocytes but is not found on peripheral blood monocytes or the human Fc Receptor-bearing cell lines HL60 or U937. The antigen is found on myeloid cells beyond the metamyelocyte stage in human marrow, on leukocytes from CML patients, and on HL-60 cells treated with dimethyl sulfoxide (DMSO) or retinoic acid. The Fc Receptor thus appears to be a late differentiation antigen on cells of myeloid lineage. Density gradients will be used to purify populations of cells at different stages of myeloid maturation from either the peripheral blood of patients with CML or HL-60 cells treated with DMSO. Fc receptors will be quantitated and characterized functionally on these purified cell populations. Immunofluorescent techniques, a sensitive radioimmunoassay, subcellular fractionation, and surface and biosynthetic labeling of proteins will be used to study the localization and biosynthesis of this plasma membrane protein during myeloid maturation in studies of isolated CML leukocytes at different stages of development, in HL-60 cells induced to differentiate with DMSO, and in normal mature PMN. The role of an internal pool of FCR in PMN will be examined as a function of the physiological and pharmacological modulation of these cells. These studies will provide information on normal, myeloid leukocyte physiology and the expression of a late differentiation antigen (the Fc-gamma R) in myeloproliferative diseases. (CS)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA038055-07
Application #
3176083
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1984-08-01
Project End
1993-01-31
Budget Start
1991-02-01
Budget End
1992-01-31
Support Year
7
Fiscal Year
1991
Total Cost
Indirect Cost
Name
State University New York Stony Brook
Department
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794