The effect of γ-interferon to inhibit macrophage-high density lipoprotein interactions is reversed by Δ12,14-prostaglandin J2J2.

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 J₂ (15d-PGJ₂), which also inhibited the IFN_γ inductin of the β2 integrin CD1 1a. 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 PPAR_γ agonists in modulating the IFN_γ-mediated macrophage effector functions relevant to atherosclerotic disease progression. [ABSTRACT FROM AUTHOR]