Age-related enhancement of 5-lipoxygenase metabolic capacity in cattle alveolar macrophages.

Abstract

Arachidonic acid (AA) metabolism was assessed in cultured alveolar macrophages (AM) obtained from newborn (9- and 23-day-old) and adult (2- and 6-yr-old) cattle. The AM were prelabeled in [3H]AA-containing medium and, thereafter, stimulated with either A-23187 or zymosan. The released radiolabeled AA metabolites were measured by high-performance liquid chromatography with on-line radiodetection. The results showed that, among different-aged cattle, the synthesis of total 5-lipoxygenase (5-LO) metabolites [leukotrienes (LT) B4, LTC4, LTD4, and 5-hydroxyeicosatetraenoic acid (5-HETE)] increased with age in spite of similar levels of phospholipase-catalyzed AA release. In response to A-23187 and zymosan, 5-LO metabolic capacity of adult cattle AM was approximately 4- and approximately 10-fold that of 9-day-old cattle AM, respectively. As 5-LO metabolic capacity increased, the release of prostaglandins and thromboxane tended to decrease. Immunoblot analysis showed that the steady-state expression of 5-LO and 5-lipoxygenase-activating protein (FLAP) also increased in an age-dependent manner. In newborn calves, AM do not produce great amounts of LTB4; this factor might contribute to insufficient polymorphonuclear leukocyte recruitment into the alveolar space and the high susceptibility to neonatal lung infection.