# STEROL METABOLISM AND HUMAN MONONUCLEAR CELL FUNCTION

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 1988 · $142,080

## Abstract

The specific aims of the proposed research are to examine in greater detail
the regulation of sterol metabolism by lipoproteins and the impact of such
regulatory effects on lymphocyte function and to determine whether
abnormalities of lipoprotein metabolism predisposing to the development of
atherosclerosis can be detected and characterized using lymphocyte
studies.  The binding and uptake of lipoproteins by lumphocytes and
subsequent regulation of endogenous sterol metabolism will be
investigated.  Lipoprotein characteristics required for lymphocyte receptor
interaction will be determined by examining various lipoprotein classes
including LDL, by chemical modification of lipoproteins to prevent binding
of the apolipoproteins B and E (apo-B and apo-E) to the receptor and by the
use of monoclonal antibodies directed against the receptor binding sites on
apo-B and apo-E that block apoprotein-receptor interaction.  The role of
LDL receptors will be studied by comparing normal lymphocytes with those
obtained from LDL receptor-negative familial hypercholesterolemia (FH)
patients and by the use of a blocking monoclonal antibody directed against
the apoprotein binding site of the LDL receptor.  Using these techniques,
lipoprotein cholesterol-dependent lymphocyte proliferation will be analyzed
by culturing cells in lipoprotein-deficient medium, blocking endogenous
sterol synthesis with specific inhibitors of the rate-limiting enzyme
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and providing
cholesterol as limiting concentrations of specific lipoproteins.
Apoprotein and receptor requirements for lipoprotein regulation of
lymphocyte sterol synthesis will be investigated by measuring
(1-14C)acetate incorporation into digitonin-precipitable sterols and the
activity of HMG-CoA reductase.  Apo-B mediated binding and uptake of
lipoproteins and regulation of LDL receptor expression by lipoproteins will
be examined using fluorescent-labeled LDL and analysis by flow cytometry
and quantification of LDL receptors using monoclonal antibodies.  Molecular
events in the regulation of LDL receptor expression and sterol biosynthesis
and the interrelationship of lymphocyte activation and sterol metabolism
will be studied by measurements of specific mRNA for LDL receptors, HMG-CoA
reductase and the mRNAs for lymphocyte activation antigens including the
interleukin-2 receptor and the transferrin receptor.  The information
generated from these studies of normal and homozygous FH lymphocytes will
be used to develop techniques to detect and characterize abnormalities in
heterozygous FH, other possible lipoprotein receptor defects and
lipoprotein abnormalities.

## Key facts

- **NIH application ID:** 3127331
- **Project number:** 5R01AI017653-07
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **SAM.gov UEI:** YZJ6DKPM4W63
- **Principal Investigator:** Peter E Lipsky
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $142,080
- **Award type:** 5
- **Project period:** 1981-05-01 → 1991-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3127331

## Citation

> US National Institutes of Health, RePORTER application 3127331, STEROL METABOLISM AND HUMAN MONONUCLEAR CELL FUNCTION (5R01AI017653-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3127331. Licensed CC0.

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