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

Min Chi Lu, Marc Peters-Golden, Douglas E. Hostetler, N. Edward Robinson, Frederik J. Derksen

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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 ~4- and ~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.

Original languageEnglish (US)
Pages (from-to)L547-L554
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume271
Issue number4 15-4
DOIs
StatePublished - Oct 1996
Externally publishedYes

Keywords

  • 5-lipoxygenase activating protein
  • arachidonate
  • leukotrienes
  • newborn
  • prostaglandins

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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