A Model For Alpha-1-Acid Glycoprotein-Mediated Immunosuppression In The Metastatic Breast Cancer Patient: Effects On The Lymphoid Cell Surface
Date of Award
Doctor of Philosophy (Ph.D.)
Lymphoid cells from metastatic breast cancer patients showed a reduced capacity to respond to the mitogen Concanavalin A as compared to lymphoid cells from normal women in the same age group. In an attempt to determine if a serum factor was partially responsible for this anomaly, sera was collected from patients with metastatic breast cancer and tested for its ability to inhibit normal lymphocyte responsiveness. Normal lymphoid cells incubated in patients' sera showed a significant decrease in their Con A, PHA-P, and PWM blastogenic response as compared to the same cells incubated in sera from age and sex-matched normal individuals. Sera from these patients were analyzed for the presence of elevated levels of (alpha)-1-acid glycoprotein (AG), an acute phase reactant which had been shown to nonspecifically suppress various immunological functions. A correlation was established between the level of AG in the serum and its ability to inhibit mitogen induced blast transformation of normal lymphoid cells. To determine if breast cancer serum with elevated AG could perturb normal lymphoid membrane function, Con A capping, studies were performed on normal lymphoid cells pre-treated with serum from a breast cancer patient or normal individual. Con A capping of normal lymphoid cells was inhibited by pre-treatment with breast cancer sera, or normal sera supplemented with AG. Exogenous addition of AG to normal sera was also capable of inhibiting surface immunoglobulin capping on B lymphocytes, as well as Con A capping. With the use of flow cytometric analysis, it was shown that the ability of AG to inhibit the capping of either receptor-ligand complex was not due to an altered capacity of these ligands to bind to the lymphoid cell surface in the presence of elevated AG. The ability of AG to interact with the lipid portion of the membrane was tested with the use of synthetic vesicles composed of phosphatidyl choline. AG was shown to displace 1-anilino-8-naphthalene sulfonate (a fluorescent surface probe) from the polar head region of the phospholipid vesicles. AG was not able to displace N-phenyl-naphthalamine (a fluorescent probe of the membrance interior) from the hydrophobic portion of the synthetic vesicles. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of author.) UMI
Biology, Microbiology; Health Sciences, Immunology
Cheresh, David Alan, "A Model For Alpha-1-Acid Glycoprotein-Mediated Immunosuppression In The Metastatic Breast Cancer Patient: Effects On The Lymphoid Cell Surface" (1982). Dissertations from ProQuest. 1299.