5-LIPOXYGENASE METABOLISM IN ALVEOLAR MACROPHAGES FROM SUBJECTS INFECTED WITH THE HUMAN-IMMUNODEFICIENCY-VIRUS

Pulmonary infection represents a major source of morbidity and mortali ty in AIDS. One important component of pulmonary host defense is the e laboration by resident alveolar macrophages (AM) of proinflammatory le ukotrienes (LT) and other 5-lipoxygenase (5-LO) metabolites of arachid onic acid (AA). In this study, we compared the 5-LO metabolic capacity of AM isolated from normal controls with two groups of HIV-infected s ubjects: (1) patients with low CD4 counts undergoing diagnostic evalua tion for pulmonary indications, and (2) volunteers without pulmonary c omplaints stratified into normal (>500) and low (<200) CD4 count group s. Compared with AM from control subjects, AM from HIV-infected subjec ts with normal and low CD4 counts demonstrated a marked reduction in L T synthesis. This reduced metabolic capacity could not be attributed t o in vivo activation because there was no increase in lavage fluid LTB (4) levels. However, there was a reduction (approximately twofold) in 5-LO protein expression in both the normal and the low CD4 subsets. 5- LO-activating protein (FLAP) expression was unchanged in cells from th e normal CD4 HIV group, but was decreased threefold in the two groups with low CD4 counts. These observations indicate that there is a grade d defect in the 5-LO metabolic capacity of AM from HIV-infected subjec ts, with decreased expression of only 5-LO in the normal CD4 group, an d decreased expression of both 5-LO and FLAP in the low CD4 group. Thi s defect would be expected to compound the immunosuppression seen in t hese subjects.