Journal of Lipid Research, Vol 24, 1512-1524, Copyright © 1983 by Lipid Research, Inc.
Immunoregulation by low density lipoproteins in man: low density lipoprotein inhibits mitogen-stimulated human lymphocyte proliferation after initial activation
JA Cuthbert and PE Lipsky
Low density lipoprotein (LDL, d 1.020-1.050 g/ml), isolated from normal
human plasma by ultracentrifugation, inhibited mitogen-stimulated
proliferation of human lymphocytes in a concentration-dependent manner. In
order to characterize the inhibition more fully, the effect of LDL on
initial lymphocyte activation and subsequent DNA synthesis was
investigated. LDL had no effect on lymphocyte blast transformation assessed
by quantitating the change in volume of the stimulated cells after a
24-hour incubation. Moreover, initial lymphocyte activation assessed by
mitogen-stimulated RNA or protein synthesis was not inhibited by LDL.
Finally, the acquisition of transferrin or T cell growth factor receptors
by the activated lymphocytes was not affected by LDL. DNA synthesis,
evaluated by measuring the incorporation of [3H]thymidine between 30 and 48
hours of culture was inhibited by LDL in a concentration-dependent manner.
The DNA content of individual mitogen-stimulated cells was analyzed by flow
cytometry after mithramycin staining. These studies confirmed that LDL
inhibited DNA synthesis in the initially activated lymphocytes. In
addition, LDL in concentrations that did not inhibit initial DNA synthesis
did suppress cell division and lymphocyte proliferation. These results
indicate that LDL inhibits lymphocyte responses by exerting inhibitory
effects on DNA synthesis, cell division, and subsequent growth of the
activated cells rather than by altering initial lymphocyte blast
transformation. LDL thus may play a role in regulating clonal expansion of
activated lymphocytes during immune responses.
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