Inhibition of human lymphocyte transformation of oxygenated sterol compounds

Journal Article · Tue Apr 01 04:00:00 EST 1980 · Cell. Immunol.; (United States)

DOI:https://doi.org/10.1016/0008-8749(80)90236-1· OSTI ID:5336268

Yachnin, S; Hsu, R

Oxygenated sterol compounds (OSC), potent inhibitors of sterol synthesis in both resting and mitogen-stimulated human lymphocytes, are capable of suppressing the DNA-synthetic response of human peripheral blood lymphocytes to mitogenic lectins, anti-human thymocyte antiserum, and the mixed lymphocyte culture. The most potent OSC are 20..cap alpha..-hydroxycholesterol and 25-hydroxycholesterol, which inhibit DNA synthesis in mitogen stimulated lymphocytes at 7.4 and 3.9 x 10/sup -6/M, respectively. Lymphocytes which have been exposed to OSC for 18 hr and washed free of inhibitor are fully capable of DNA synthesis when subsequentlc challenged with mitogen. Suppression of DNA synthesis by OSC is not apparent during the first 24-40 hr of culture. The inhibition of lymphocyte DNA synthesis by OSC can be partially reversed by the addition of 10/sup -2/M mevalonate to the culture. Sterol synthesis by mitogen-stimulated lymphocytes is enhanced by culturing them in medium supplemented with lipoprotein (and cholesterol-)-depleted serum. In such medium, the 50% inhibitory doses of 25-hydroxycholesterol for suppression of both mitogen-stimulated lymphocyte DNA and sterol synthesis are approximately equal (approx. =3 x 10/sup -7/M). Sterol synthesis is a necessary, but not sufficient, part of the program of lymphocyte proliferative response to mitogens; the evidence presented suggests that lymphocytes can utilize exogenous sterol at least partially for the purpose of cell replication.

• Research Organization: Univ. of Chicago, IL
• OSTI ID: 5336268
• Journal Information: Cell. Immunol.; (United States), Journal Name: Cell. Immunol.; (United States) Vol. 51:1; ISSN CLIMB
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
550300* -- Cytology
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOSYNTHESIS
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL CULTURES
CELL PROLIFERATION
CONNECTIVE TISSUE CELLS
DNA REPLICATION
HYDROXY COMPOUNDS
IMMUNE REACTIONS
INHIBITION
LEUKOCYTES
LYMPHOCYTES
MAMMALS
MAN
MATERIALS
MITOGENS
NUCLEIC ACID REPLICATION
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PRIMATES
SENSITIVITY
SOMATIC CELLS
STEROIDS
STEROLS
SYNTHESIS
VERTEBRATES