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The effect of γ‐interferon to inhibit macrophage‐high density lipoprotein interactions is reversed by Δ 12,14 ‐prostaglandin J 2 J 2
Author(s) -
Zuckerman Steven H.,
Panousis Constantinos,
Mizrahi Jacques,
Evans Glenn
Publication year - 2000
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-000-0640-9
Subject(s) - scavenger receptor , cd36 , macrophage , receptor , cytokine , endocrinology , medicine , lipoprotein , biology , interferon gamma , chemistry , microbiology and biotechnology , immunology , biochemistry , cholesterol , in vitro
Macrophage activation has been recognized as playing a central role in chronic inflammatory diseases in general and more specifically, in the vascular wall during the progression of atherosclerotic lesions. Macrophage‐activating factors present within the atherosclerotic lesion include the colony‐stimulating factors and gamma interferon (IFN γ ). In the present study, the effects of IFN γ on macrophage binding and uptake of fluorochrome‐labeled high density lipoprotein (HDL) were investigated by flow cytometry and by measuring the amount of the type B scavenger receptors CD36 and scavenger receptor type B (SR‐BI) by Northern blot analysis. IFN γ ‐, but not granulocyte macrophage colony‐stimulating factor (GM‐CSF)‐treated murine peritoneal macrophages displayed a two‐ to threefold decrease in Dil‐labeled HDI uptake. This effect was observed in the absence of a comparable decrease in SR‐BI meassage and protein or CD36 message. This decrease in both HDL binding and uptake was reversed by the peroxisome proliferator‐activated receptor gamma (PPAR γ ) agonist, Δ 12,14 ‐prostaglandin J 2 (15d‐PGJ 2 ), which also inhibited the IFN γ inductin of the β2 integrin CD1 1a. Furthermore, 15d‐PGJ 2 increased the expression of SR‐BI and CD36 message and SR‐BI protein which was reflected in an increase in HDL binding and uptake. These results suggest a role for PPAR γ agonists in modulating the IFN γ ‐mediated macrophage effector functions relevant to atherosclerotic disease progression.