Role of the 5-Lipoxygenase–activating Protein (FLAP) in Murine Acute Inflammatory Responses

摘要: Leukotrienes are potent inflammatory mediators synthesized from arachidonic acid (AA) predominately by cells of myeloid origin. The synthesis these lipids is believed to be dependent not only on the expression enzyme 5-lipoxygenase (5-LO), which catalyzes first steps in leukotrienes, but also a nuclear membrane protein termed 5-LO–activating (FLAP). To study relationship two proteins mediating production leukotrienes vivo and determine whether FLAP has additional functions various processes, we have generated mouse line deficient this protein. FLAP-deficient mice develop normally healthy. However, an array assays comparing reactions normal controls revealed that plays role subset reactions. Although examination DTH IgE-mediated passive anaphylaxis showed no difference between wild-type animals, without possessed blunted response topical AA had increased resistance platelet-activating factor–induced shock compared controls. Also, edema associated with Zymosan A–induced peritonitis was markedly reduced animals lacking FLAP. differences relate solely deficit leukotriene production, or they reflect for inflammation, 5-LO–deficient animals. Evaluation 5-LO indicated during responses upon availability did support beyond its production.