166 Lipopolysaccharide Priming of Macrophages

Macrophages play impor tant roles in inflammation and host defense against bacterial infection. T h e metabolites o f arachidonic acid (20:4) 1 are impor tant modulators o f these responses (1). When macrophages interact with stimuli such as an immune complex or a bacter ium, phospholipases are activated and 20:4 is l iberated f rom plasma mem b ran e phospholipids. T h e free 20:4 is then quantitatively oxygenated by ei ther the lipoxygenase pathway to leukotr iene C (LTC) and hydroxyeicosatet ranoic acids (HETEs) or along the cyclooxygenase pathway to prostaglandin E2 (PGE2) and prostacyclin (PGI2) (2-5). Very little is known about the cellular events involved in the activation and control o f 20:4 metabolism. We repor t here that bacterial LPS, at concentrat ions similar to that found in the blood o f patients with gram-negative bacteremia (6) pr ime macrophages for a greatly increased capacity to secrete 20:4 metabolites.