Plasma lipoproteins of the very low (VLDL) and low (LDL) density classes block the activation and cell cycle progression of lymphocytes. Lipoproteins can suppress the accessory cell- independent priming of lymphocytes by mitogen, the capacity of accessory cells to deliver a requisite progression signal to lymphocytes, and the G1/S transition of fully activated lymphocytes. In this proposal the focus is lipoprotein suppression of the phosphatidylinositol (PI) responses of the priming event and an accessory cell-dependent activation event. The phosphatidylinositol responses can be suppressed by apoE and apoB constituents of the lipoproteins as well as by synthetic peptides corresponding to domains in the apoproteins. Suppression is mediated by an immunoregulatory receptor (IR-R) on lymphocytes which recognizes apoE and apoB. The proposal has three specific aims. (1) The IR-R will be purified and characterized. (2) The structural features of apoE, apoB and functionally related peptides required to regulate the PI responses will be elucidated, and the interaction of these peptides with the IR-R will be assessed. (3) The molecular basis by which the peptides influence the PI responses will be delineated, focusing on the importance of the lymphocyte's PI-specific phospholipase C. Achievement of these aims will provide fundamental information about a lipoprotein receptor and about the nature and control of phosphatidylinositol metabolic activity associated with the movement of nonproliferating cells from G0 into and through the G1 phase of the cell cycle.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HL027333-10
Application #
3485914
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1980-07-01
Project End
1992-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
10
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Cincinnati
Department
Type
Schools of Medicine
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
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