Regulation of 5-lipoxygenase metabolism in mononuclear phagocytes by CD4 Tlymphocytes

Alveolar macrophages (AM) are the primary resident effector cells in the al veolus. Leukotrienes (LT) are secreted by AM in their role as defender of t he lung. 5-Lipoxygenase (5-LO) catalyzes the synthesis of LT in association with 5-LO-activating protein, termed "FLAP." AM demonstrate increased 5-LO metabolism compared to peripheral blood monocytes (PBM). Activated lymphoc ytes release mediators which upregulate 5-LO metabolism in PBM. The lymphoc yte population of the lung consists predominantly of CD4+ helper constituti vely "activated" T cells. We hypothesized that mediators released by pulmon ary CD4+ T cells may upregulate and maintain of 5-LO metabolism in PBM as t hey enter the alveolar space and differentiate into AM. 5-LO metabolism in AM from CD4-depleted mice demonstrated reduced LT synthesis (LTC4: 66.9 +/- 8%; LTB4 61.4 +/- 6.2% control). The decrease in 5-LO metabolism was assoc iated with reduced FLAP (30.1 +/- 14.5% of control) and 5-LO expression (49 +/- 13.7% of control). This defect in AM 5-LO metabolism in CD4-depleted m ice was further associated with reduced LTC4 levels in bronchoalveolar lava ge (BAL) fluid. In summary,factors secreted constitutively by lung lymphocy tes, in particular CD4 cells, contribute to the increased 5-LO metabolism i n AM.