IFN-gamma receptors on human tumor cells: relationship between receptor ligand interactions and induction of IFN-gamma response.
Scatchard analysis of 125I-IFN-gamma binding on fresh lymphoid and myeloid tumor cells derived from 34 leukemia patients and on normal cells obtained from 14 healthy individuals revealed similar high affinity binding with a mean Kd of around 2 X 10(-11) M in 14/14 normal and 30/34 malignant cells, but large quantitative differences in the receptor number of malignant cells with a range of 300 to 12,000 receptors/cell. In contrast, normal lymphoid and myeloid cells expressed consistantly low numbers of receptors with a mean of 300 and 1,000 receptors/cell, respectively. Kinetic studies of IFN-gamma binding in relation to induction of HLA-DR antigens in established cell lines revealed the existence of close correlations between the quantity of receptor ligand interaction and induction of IFN-gamma response, indicating that at limiting IFN-gamma concentrations the height of response is controlled by the number of expressed membrane receptors. In the light of the observed quantitative differences in IFN-gamma receptors on various tumors, this finding may have implications for the definition of therapeutically effective IFN-gamma doses.
D001853:Bone Marrow / Q000502:physiology; D002460:Cell Line; D006681:HLA-D Antigens / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D007938:Leukemia / Q000503:physiopathology*; D008214:Lymphocytes / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology*; D017471:Receptors, Interferon; D013997:Time Factors
D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D007371:Interferon-gamma