Enhancement of the antigen-presenting function of monocytes by cholesterol: possible relevance to inflammatory mechanisms in extrinsic allergic alveolitis and atherosclerosis

Abstract

SUMMARY Extrinsic allergic alveolitis (EAA) (synonym: hypersensitivity pneumonitis) is a hypcrscnsitivity lung disease characterized by lymphocytic infiltrates in the pulmonary interstitial tissues. We have previously reported that the numbers of lymphocytes in bronchoalveolar lavage (BAL) samples in this disease correlate with levels of cholesterol and neutral lipid-laden “foamy” macrophages. We have also reported that the macrophages express an increased density of MHC class II antigens (in particular HLA-DQ) which are known to be essential for antigen recognition by T lymphocytes. The aim of the present study was to explore whether cholesterol is capable of enhancing the antigen-presenting function of mononuclear phagocytes by modulating the expression of HLA-D region products. Incubation of purified monocytes from healthy volunteers with cholesterol in scrum-free medium induced a significant increase in both the percentages of monocytes expressing HLA-DQ (P<0.02) and in the intensity of expression of the three HLA-D sub-region products. HLA-DQ. -DP and -DR (P<0.02, <0.01, <005. respectively). The cholesterol pre-incubated monocytes also exhibited enhanced antigen-presenting function (P<0.05), compared with controls pre-incubatcd without cholesterol. These findings indicate that increases in cholesterol in the extracellular milieu may augment antigen presentation by modulating the expression of HLA-D region products on antigen-presenting cells. Apart from EAA. this observation may also have relevance to inflammatory mechanisms in atherosclerosis, where‘foamy’ macrophages also occur in association with hypercholestcrolaemia.