The effect of γ‐interferon to inhibit macrophage‐high density lipoprotein interactions is reversed by Δ 12,14 ‐prostaglandin J 2 J 2

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 (IFNgamma). In the present study, the effects of IFNgamma 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. IFNgamma-, but not granulocyte macrophage colony-stimulating factor (GM-CSF)-treated murine peritoneal macrophages displayed a two- to threefold decrease in Dil-labeled HDL uptake. This effect was observed in the absence of a comparable decrease in SR-BI message and protein or CD36 message. This decrease in both HDL binding and uptake was reversed by the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist, 15-deoxy-delta12,4-prostaglandin J2 (15d-PGJ2), which also inhibited the IFNgamma induction of the beta2 integrin CD11a. Furthermore, 15d-PGJ2 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 PPARgamma agonists in modulating the IFNgamma-mediated macrophage effector functions relevant to atherosclerotic disease progression.