The effect of γ-interferon to inhibit macrophage-high density lipoprotein interactions is reversed by 15-deoxy-Δ12,14-prostaglandin J2

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 gamma). In the present study, the effects of IFN gamma 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 gamma-, but not granulocyte macrophage colony-stimulating factor (CM-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 (PPAR gamma) agonist, 15-deoxy-Delta (12,14)4-prostaglandin J(2) (15d-PGJ(2)), which also inhibited the IFN gamma induction of the beta2 integrin CD11a. 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 gamma agonists in modulating the IFN gamma -mediated macrophage effector functions relevant to atherosclerotic disease progression.